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Fibromyalgia is characterized by diffuse musculoskeletal pain and fatigue. There are limited data about systemic steroid treatment of patients with fibromyalgia in the English literature. Patients with fibromyalgia with ongoing diffuse musculoskeletal pain despite standard treatment, extreme fatigue and elevated C-reactive protein (CRP) levels without evidence of synovitis, or other source of inflammation, were asked to participate in our study. After consent, demographic, clinical and laboratory parameters in addition to body mass index were documented. These patients were interviewed and asked to answer the Revised Fibromyalgia Impact Questionnaire (FIQR) just prior, 1 and 4 weeks following 14 mg depot betamethasone intramuscular injection. Twenty-three patients were recruited and 21 completed the study. 19 patients were women with mean age of 42±10.12 and CRP level of 14.1±3.96 mg%, and all had negative rheumatoid factor and antinuclear antibodies. All patients had significant improvement in all of the FIQR parameters, at 1 and 4 weeks, except memory, anxiety and balance. It can be concluded that systemic intramuscular depot betamethasone injection seems to have a favorable effect in patients with fibromyalgia with elevated CRP levels for at least 4 weeks.

Aim:Certolizumab pegol (CZP), an Fc-free, PEGylated tumor necrosis factor inhibitor (TNFi), has shown rapid and sustained reduction in signs and symptoms of rheumatoid arthritis (RA). Elevated rheumatoid factor (RF) level has been associated with RA disease progression and poorer TNFi response. We assessed the efficacy of CZP in patients with early and established RA across baseline RF levels. Methods:This post-hoc analysis included data from 6 trials: C-OPERA (NCT01451203), pooled RAPID trials (RAPID-1 [NCT00152386], RAPID-2 [NCT00160602], J-RAPID [NCT00791999], RAPID-C [NCT02151851]), and EXXELERATE (NCT01500278). Patients who received CZP or placebo/comparator with methotrexate (MTX) were categorized by baseline RF quartiles. Efficacy was assessed with Disease Activity Score-28 erythrocyte sedimentation rate (DAS28-ESR). Results:Overall, 316, 1537, and 908 patients were included in C-OPERA, pooled RAPID trials, and EXXELERATE, respectively. Patient demographics and baseline disease characteristics were similar between treatment groups and across RF quartiles. DAS28-ESR low disease activity (LDA) and remission (REM) rates were numerically higher in the CZP + MTX group than PBO + MTX group at weeks 12 and 24, across RF quartiles. LDA and REM rates in the CZP + MTX groups were comparable across RF quartiles at weeks 12 and 24. Mean DAS28-ESR decreased from week 0 to week 24 in the CZP + MTX groups, across RF quartiles. Conclusion:CZP showed steady efficacy across baseline RF quartiles in patients with early and established RA, over 24 weeks. CZP treatment may be considered in patients with RA irrespective of baseline RF levels and time from diagnosis.

Dogs with infectious arthritis may occasionally exhibit positive serum antinuclear antibody (ANA) and rheumatoid factor (RF) titers; however, relevant data are sparse for arthritis secondary to canine leishmaniosis (CanL) caused by Leishmania infantum. We determined the prevalence of positive serum ANA and RF titers in dogs with arthritis secondary to CanL. Blood samples from adult, client-owned dogs with purulent arthritis secondary to CanL, without any comorbidities, were collected for diagnostic purposes. Serum ANA titers were measured by immunoperoxidase test and RF titers by the Rose–Waaler latex test. Twelve of 23 dogs enrolled prospectively in our study had clinical arthritis, and 11 of 23 had subclinical arthritis. Based on LeishVet clinical staging, 7 dogs had clinical stage II disease, 11 had clinical stage III disease, and 5 had stage IV. None of the 23 dogs was seropositive for ANA; 3 of 23 were positive for RF. ANA and/or RF seropositivity, in dogs with CanL-associated arthritis, appears to be weak, if present at all. Based on our results, positive serum ANA and RF titers should not be expected in dogs with arthritis secondary to CanL.

Introduction Hemogram parameters have been recently proposed as markers of inflammation in various studies from different parts of the world. Two of these hemogram parameters are red cell distribution width (RDW) and mean platelet volume (MPV). Aim To evaluate the relation between RDW and MPV with disease activity of rheumatoid arthritis. To assess whether RDW and MPV can be used to follow disease activity in RA patients. Methods This is an observational cross-sectional study that was carried out on 60 rheumatoid arthritis patients who fulfilled the ACR/EULAR2010 classification criteria of RA attending to Rheumatology and Rehabilitation inpatient and outpatient clinics at Zagazig University Hospitals. All cases were subjected to full history taking, clinical examination, and laboratory investigations; differential complete blood picture (CBC), acute phase reactants (CRP and ESR), rheumatoid factor (RF) and anti-cyclic-citrullinated peptide (anti-CCP) antibodies. Disease activity was measured by disease activity score 28 (DAS28). Results The cut-off levels of RDW and MPV were 14.85 and 11.25. Patients with RDW > 14.85 had higher Disease Activity Score 28 (DAS28; p = 0.0003), ESR (p = 0.0001) and CRP (p = 0.0001). RDW was positively correlated with disease activity markers (ESR, CRP and DAS28) in rheumatoid arthritis patients. But, DAS28 was not different between patients with MPV > 11.25 and Conclusion RDW was strongly correlated with disease activity. Also, RDW was better than ESR and CRP in detecting RA disease activity. According to these findings we suggest that RDW can be used in clinics to follow disease activity. In addition, RDW is widely available; as it's usually included in routine complete blood picture and there will be no need for further cost.

IntroductionAnti-Ro52/tripartite motif-containing protein 21 (TRIM21) IgG is one of the most common autoantibodies found in systemic autoimmune diseases and is typically found in conjunction with anti-Ro60 and/or anti-La. A retrospective, cross-sectional study was undertaken to examine the clinical and laboratory features of two serological subsets: patients with anti-Ro52/TRIM21 autoantibodies in the absence of anti-Ro60 and anti-La (isolated anti-Ro52/TRIM21) and patients with anti-Ro52/TRIM21 in the presence of anti-Ro60 and/or anti-La.MethodsOver a 12-month period, patients tested positive for anti-Ro52/TRIM21 via line immunoassay (LIA) at the Westmead Hospital (Australia) immunopathology laboratory were included. The presence of anti-Ro60 and/or anti-La via same LIA was noted. Associated laboratory and medical records were perused to extract demographic, laboratory, and clinical information.ResultsThere were 346 patients within the study period, and 39.9% of the patients positive for anti-Ro52/TRIM21 lacked anti-Ro60/anti-La autoantibodies. Isolated anti-Ro52/TRIM21 patients tend to be older, have lower anti-Ro52/TRIM21 titres, have lower rheumatoid factors, and have lower proportions of neutropaenia compared to patients who were positive for anti-Ro52/TRIM21 and anti-Ro60/La. This occurred independent to diagnoses of Sjögren’s syndrome or systemic lupus erythematosus. Coexisting neurological syndromes, pulmonary pathologies, and malignancies were more prevalent in the isolated anti-Ro52/TRIM21 subset.ConclusionsPatients with isolated anti-Ro52/TRIM21 tend to have distinct and important clinical and laboratory associations. It is unclear if these patients evolve or remain a stable subset and how they originate immunologically. Longitudinal and prospective studies are required to ascertain the overall predictive and prognostic value of this stratification.Key Points• Anti-Ro52/TRIM21 is an autoantibody found in autoimmunity and non-immunological conditions.• Sixty percent of anti-Ro52/TRIM21 patients are positive for anti-Ro60.• Isolated anti-Ro52/TRIM21 has reduced anti-Ro52/TRIM21 and rheumatoid factor titres.• Isolated anti-Ro52/TRIM21 is associated with anaemia and malignancies.

The aim of the Paediatric Rheumatology International Trials Organisation (PRINTO) juvenile idiopathic arthritis (JIA) classification criteria, which is still in development, is to identify homogeneous groups of JIA patients. This study was undertaken to compare International League of Associations for Rheumatology (ILAR) JIA classification criteria and PRINTO JIA classification criteria using data from the ReACCh-Out (Research in Arthritis in Canadian Children, Emphasizing Outcomes) cohort.We used clinicobiologic data recorded within 7 months of diagnosis to assign a diagnosis of JIA and identify subcategories of JIA among 1,228 patients according to the 2 JIA classification systems. We compared the proportions of patients classified and the alignment of classification categories with clinicobiologic subtypes and adult arthritis types.The PRINTO criteria classified 244 patients (19.9%) as having early-onset antinuclear antibody-positive JIA, 157 (12.8%) as having enthesitis/spondylitis-related JIA, 38 (3.1%) as having systemic JIA, and 10 (0.8%) as having rheumatoid factor-positive JIA. A total of 12% of patients were unclassifiable using the ILAR criteria, while 63.3% were unclassifiable using the PRINTO criteria (777 with other JIA and 2 with unclassified JIA). In sensitivity analyses,50% of patients remained unclassifiable using the PRINTO criteria. Compared to the PRINTO criteria, ILAR JIA categories aligned better with clinicobiologic subtypes in 131 patients (χCurrently identified PRINTO disorders can only be used to classify a minority of JIA patients, leaving a large proportion of JIA patients with other disorders requiring further characterization. Current PRINTO JIA classification criteria do not align better with clinicobiologic subtypes or adult forms of arthritis compared with the older ILAR classification system.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which mainly affects small joints, occurs most commonly in middle-aged adults, and can be fatal in severe cases. The exact etiology of RA remains unknown. However, uncontrolled expression of pro-inflammatory cytokines and chemokines can contribute to the pathogenesis of RA.In the current study, we assessed the potential of serum concentrations of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, IL-8, and C-C motif chemokine ligand (CCL)5 as early predictive markers for RA.In addition to clinical examination, blood samples were collected from 100 Saudi patients recently diagnosed with early RA for basic and serological tests, including rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Sera of 32 healthy individuals were used as controls. Specific enzyme-linked immunosorbent assay was used to quantify the serum IL-1β, IL-6, TNF-α, IL-8, and CCL5 levels in the samples.Our results indicated that RF, CRP, and ESR levels were higher in RA patients compared to controls. Furthermore, serum levels of IL-1β, IL-6, IL-8, and CCL5, but not TNF-α, significantly increased in RA patients compared to controls.Overall, the findings suggested that IL-1β, IL-6, IL-8, and CCL5 can be used as biomarkers in the early diagnosis of RA.

Introduction/objectivesPsychological stress worsens rheumatoid arthritis (RA) disease activity, and the COVID-19 pandemic has increased stress/anxiety in rheumatic patients. The purpose of this study was to determine if stress during the COVID-19 pandemic specifically impacts RA disease activity as reported by the patient.MethodThis was a cross-sectional COVID-19 RA survey study. University of California, Los Angeles rheumatology clinic patients were emailed a link to a survey in July and November 2020. The 30-question survey pertained to COVID-19-related stress, RA disease activity, and demographics. For the survey responders, anti-cyclic citrullinated antibody, rheumatoid factor, and age were extracted from the electronic health record. Analyses were performed to examine the association between the 4-item Perceived Stress Scale (PSS-4) and other COVID-19-related stress measures with the Routine Assessment of Patient Index Data 3 (RAPID3).ResultsA total of 1138/5037 subjects completed the emailed survey (22.6% response rate). When examining responses across RAPID3 categories (near remission, low, moderate, and high disease severity), there were significant increases in PSS-4 and other stress variables. Multiple linear regression models showed that PSS-4, financial stress, age, seropositivity, disease duration, and Black race were independently associated with worsened RAPID3 scores, when controlling for other confounding factors.ConclusionsThis study suggests that stress overall negatively impacts RAPID3, and Black RA patients had a higher RAPID3 scores during the COVID-19 pandemic. Despite colossal efforts to combat the pandemic, RA patients currently suffer from stress/anxiety, and methods to mitigate these psychological effects are needed.

Rheumatoid arthritis (RA) is a frequent cause of interstitial lung disease (ILD); however, the impact of rheumatoid factor and anti-citrullinated peptide antibody seropositivity in ILD without connective tissue disease (CTD) is unclear. We examined the association of seropositivity with ILD progression, mortality and response to immunosuppression in non-CTD ILD.A total of 1570 non-CTD patients (with idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, interstitial pneumonia with autoimmune features or unclassifiable ILD) and 181 RA-ILD patients were included from a prospective registry. Longitudinal forced vital capacity (FVC), transplant-free survival and incidence of progressive fibrosing-ILD (PF-ILD) were compared between seronegative non-CTD ILD (reference group), seropositive non-CTD ILD and RA-ILD using linear mixed-effect and Cox proportional hazards models adjusted for age, sex, smoking pack-years and baseline FVC. Interaction between seropositivity and immunosuppression on FVC decline was assessed in patients with ≥6 months of follow-up before and after the treatment.Two hundred and seventeen (13.8%) patients with seropositive non-CTD ILD had similar rates of FVC decline and transplant-free survival compared to seronegative non-CTD ILD, but more frequently met the criteria for PF-ILD (hazard ratio [HR] = 1.35, p = 0.004). RA-ILD had slower FVC decline (p = 0.03), less PF-ILD (HR = 0.75, p = 0.03) and lower likelihood of lung transplant or death (HR = 0.66, p = 0.01) compared to seronegative non-CTD ILD. No interaction was found between seropositivity and treatment on FVC decline in non-CTD ILD.Seropositivity in non-CTD ILD was not associated with improved outcomes or treatment response, highlighting the importance of other disease features in determining prognosis and predicting response to immunosuppression.

B cell antigen receptor (BCR) interactions are crucial mediators of cell-autonomous signaling which is a hallmark feature of neoplastic B cells in chronic lymphocytic leukemia (CLL). Here, through the use of a previously established cellular reconstitution system, we dissected the molecular mechanisms for the occurrence of autonomous signaling, focusing on the role of homotypic interactions between membrane-bound BCR and between BCR and soluble immunoglobulins (Ig) counterparts. Our current study showed that distinct pattern of somatic hypermutation as well as class-switch recombination events selectively shape the clinical course and outcome of different CLL subsets. In particular, we identified the expression of IGLV3-21*01 (allele 01) light chain (LC) as a risk factor for developing severe CLL through the acquisition of a single point mutation at the junction between the variable and constant LC genes, pointing out the need for more inclusive criteria for prognosis definition in CLL. Furthermore, here we provided insights into the role of acquired somatic hypermutations in the process of leukemogenesis, putting forward the idea that autonomous BCR signaling might be a conducive factor for the acquisition of novel mutations. In addition, we revealed the implications of isotype-switch in CLL subset 4 BCRs by analyzing the role of IgM and IgG isotypes in proliferation and response to treatment as well as in the process of leukemogenesis. Consistently, we reported that isotype-switch is triggered by binding to self-antigens and through the use of wild-type mice, we supported the view that isotype-switch to IgM is relevant to confer indolent clinical course to CLL subset 4 cases. Besides, in line with our previous studies, we focus here on the interaction between soluble autoreactive immunoglobulins and their antigens. In particular, using insulin as autoantigen, our group described the occurrence of insulin-specific IgM autoantibodies that regulate blood glucose metabolism showing that low-affinity insulin-specific IgM autoantibodies generated during primary immune response neutralize insulin (primary IgM, pIgM), while high-affinity insulin-specific IgM autoantibodies, generated during memory responses, exert a protective role on insulin thereby preventing its degradation (protective regulatory IgM, PR-IgM). Our current data revealed that affinity maturation is crucial for the definition of autoantigen-antibody interaction, corroborating previous findings that a high-affinity IgM autoantibody has a protective role on its target. Similarly, we extended these findings to rheumatoid factor (RF) and its target IgG. By using wild-type animals, we show in vivo that high affinity RF stabilizes IgG regardless of its pathogenic or therapeutic nature. Conversely, here we demonstrate that low affinity RF exerts neutralizing effects on IgG. Notably, while high affinity RFs are mainly found in rheumatoid arthritis (RA) patients, low affinity RFs are present in normal individuals and might play a role in regulation of physiological processes. Altogether, we put forward the idea that an excess of high affinity RFs in the concomitant presence of potentially harmful autoreactive IgGs result in IgG stabilization and culminates in autoimmune diseases such as RA. On the contrary, we suggest that low affinity RFs found in healthy individuals take part to the clearance of IgGreactive B cells thereby contributing to IgG homeostasis. Collectively, we propose that the affinity of RF for its target shapes the outcome of the interaction with IgG possibly opening up to novel therapeutic strategies. Altogether, this study provides relevant molecular and biological insights into the interactions between membrane-bound and soluble immunoglobulins pointing towards the significance of these recognitions in the context of malignant neoplastic transformation and autoimmunity.

ObjectiveTo investigate the associations between the Patient Global Assessment (PGA) and measures of disease activity in patients with rheumatoid arthritis (RA) in relation to disease duration and autoantibody status.Methods1412 patients from three independent cohorts were studied: a prospective cohort of 810 patients with early RA followed up for 24 months; a cross-sectional cohort of 210 patients with established RA in low disease activity; a cross-sectional cohort of 401 patients with established RA in moderate-to-high disease activity. Correlations of the PGA were analysed by Pearson’s coefficients and multivariable linear regression at baseline and at months 6, 12 and 24 in the overall populations and after stratification for autoantibody subgroup and remission status (Boolean remission, PGA near remission and non-remission).ResultsIn patients with early RA in non-remission, swollen joints correlated independently with the PGA; the correlation became progressively weaker but persisted at all time points in autoantibody-positive patients (adjusted r=0.30–0.12) but lost significance after month 12 in autoantibody-negative patients. Swollen joints independently correlated with the PGA also in near remission until month 12 (adjusted r=0.18–0.16) in autoantibody-positive patients. No independent correlations of inflammatory variables were instead found in patients with established RA irrespective of disease activity and autoantibody status.ConclusionsIn the early phases of RA, particularly in autoantibody-positive patients, inflammatory variables directly correlate with the PGA across different disease activity states. The optimal cut-off values of the PGA capable of identifying absence of disease should be better explored in relation to disease duration and autoantibody status.

Background and objectives In Spain, epidemiological studies of the prevalence of diffuse interstitial lung disease (ILD) in rheumatoid arthritis (RA) are limited. Our objective was to estimate the prevalence of symptomatic ILD in RA and its characteristics in our area. Materials and methods In our hospital's interdisciplinary rheumatology and pulmonology clinic, a prospective longitudinal observational study was designed in which we included RA with respiratory symptoms and ILD confirmed by high resolution computed tomography. Results Of the 2729 people with RA in our area, 47 had symptomatic ILD, estimating a prevalence of symptomatic ILD in RA of 1.72% (95% CI 1.26-2.29) with an age at diagnosis of RA of 57.3 ± 13.3 years. It was more frequent in men, 60.6% had a history of smoking, and 84.3% and 84.7% had rheumatoid factor (RF) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies, respectively. The most frequent pattern was usual interstitial pneumonitis (UIP), appearing in 28 (31.1%). Nonspecific interstitial pneumonia (NSIP) was more frequent in women, while the combined pulmonary fibrosis-emphysema (CPFE) syndrome presented exclusively in men. Conclusions We have analysed the prevalence of symptomatic RA-ILD in our area, which is lower than expected, probably in relation to the definitions used. We have also described that the UIP pattern is the most frequent in RA in our environment, followed by the NSIP. Lastly, we have analysed the prevalence of CPFE in RA, which reaches 13%, for the first time.

Rheumatoid arthritis (RA) patients often develop rheumatoid factors (RFs), antibodies that bind IgG Fc, and anti-modified protein antibodies (AMPAs), multireactive autoantibodies that commonly bind citrullinated, homocitrullinated, and acetylated antigens. Recently, antibodies that bind citrulline-containing IgG epitopes were discovered in RA, suggesting that additional undiscovered IgG epitopes could exist and that IgG could be a shared antigen for RFs and AMPAs. This study was undertaken to reveal new IgG epitopes in rheumatic disease and to determine if multireactive AMPAs bind IgG.Using sera from patients with RA, systemic lupus erythematosus, Sjögren's disease (SjD), or spondyloarthropathy, IgG binding to native, citrulline-containing, and homocitrulline-containing linear epitopes of the IgG constant region was evaluated by peptide array, with highly bound epitopes further evaluated by enzyme-linked immunosorbent assay (ELISA). Binding of monoclonal AMPAs to IgG-derived peptides and IgG Fc was also evaluated by ELISA.Seropositive RA sera showed high IgG binding to multiple citrulline- and homocitrulline-containing IgG-derived peptides, whereas anti-SSA+ sera from SjD patients showed consistent binding to a single linear native epitope of IgG in the hinge region. Monoclonal AMPAs bound citrulline- and homocitrulline-containing IgG peptides and modified IgG Fc.The repertoire of epitopes bound by AMPAs includes modified IgG epitopes, positioning IgG as a common antigen that connects the otherwise divergent reactivities of RFs and AMPAs.

Palindromik romatizma (PR), eklemlerde kalıcı hasara neden olmaksızın alevlenmeler şeklinde ağrı, şişlik ve eritem ile karakterize klinik bir sendromdur. Literatürde, PR hastalarının %39-68’inde Romatoid faktör (RF) ve antisiklik sitrüline peptid (anti-CCP) antikor pozitifliği bulunmaktadır. Literatürde seropozitif ve seronegatif PR hastalarının klinik özelliklerini karşılaştıran çok az çalışma olup hala aydınlatılmamış birçok nokta vardır. Bu çalışmada kliniğimizde takipli PR tanılı hastaların demografik ve klinik özelliklerinin değerlendirilmesi, seropozitif ve seronegatif PR hastalarının karşılaştırılması planlandı. Çalışma retrospektif, kesitsel bir çalışma olarak tasarlandı. Otuz bir hasta tarandı ve dahil etme ve dışlama kriterlerini karşılayan 21 hasta çalışmaya alındı. Hastaların ortanca yaşı 43 yıl, ortanca takip süreleri 18 ay ve ortanca alevlenme süresi 3 gündü. Seronegatif grupta 12 hasta yer alırken seropozitif grupta 9 hasta mevcuttu. Seropozitif grubun ortanca yaş değeri daha yüksekti (55 yıl vs 42 yıl, p=0,023). Alevlenme süresi ve sigara içme süresi seropozitif grupta daha uzun olmasına rağmen istatistiksel olarak anlamlı bulunmadı (Sırasıyla, 4 gün vs 2 gün ve 28,3 paket/yıl vs 9,7 paket/yıl). Eşlik eden komorbideteler seronegatif hastalarda daha fazla olmasına rağmen istatistiksel olarak anlamlı değildi. Ortalama lenfosit değerleri ise seropozitif grupta anlamlı daha yüksekti (p=0,037). Sonuç olarak, seropozitif PR hastalarının ortanca yaşları negatif olan hastalara göre daha yüksek olduğu ve ortalama lenfosit değerlerinin seropozitif hastalarda daha yüksek olduğu bulundu., Palindromic rheumatism (PR) is a clinical entity, which is characterized by remittent flares of pain, swelling and erythema around the joints that do not lead to persistent damage. In the literature, the frequencies of rheumatoid factor (RF) positivity and anti-cyclic citrullinated peptide (anti-CCP) antibody positivity have been reported as 39-68% in patients with PR. To our knowledge, studies investigating the comparison of clinical features of seronegative and seropositive patients are scarce. We aimed to assess demographic data and clinical characteristics of PR patients who followed in our clinic and to compare these features between seronegative and seropositive patients. The current study was designed as retrospective and cross-sectional. Thirty-one patients were screened and 21 patients who met the inclusion and exclusion criteria were included in the study. The median age, median follow-up duration, and median flare duration were 43 years, 18 months, and 3 days, respectively. Twelve patients were in seronegative group while 9 patients were in seropositive group. The median age was higher in seropositive patients than in seronegative patients (55 vs. 42 years, p=0.023). Even though the duration of flare and smoking cigarette were higher in seropositive group, there was not statistically significant difference between groups (4 vs. 2 days and 28.3 vs. 9.7 packs/years, respectively). Comorbidities were common in seronegative patients but there was not statistically significant difference between groups. Mean lymphocyte count was statistically significantly higher in seropositive group (p=0.037). In conclusion, the median age and mean lymphocyte count were higher in seropositive group than in seronegative group.

Aim of the work: To evaluate the frequency of anti-carbamylated protein (anti-CarP) antibodies positivity in female rheumatoid arthritis (RA) patients; to study their association with different disease aspects clinically and radiologically and to assess their potential predictive role of RA disease compared to other autoantibodies. Patients and methods: Fifty-one RA female patients and 44 age-matched controls were studied. Duration of morning stiffness, disease activity score (DAS28) and health assessment questionnaire (HAQ) were assessed. Laboratory investigations included acute phase reactants, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and anti-CarP antibodies. Conventional radiography of both hands and feet was performed and assessed by a simple erosion narrowing score (SENS). All patients were evaluated by ultrasound 7 (US7) score. Results: The mean age of patients was 46.9 ± 8.6 years with disease duration of 6.2 ± 5.3 years. Anti-CarP antibody was positive in 52% and 54.5% of patients seronegative for anti-CCP and RF respectively. RF was positive in 40 (78.4), anti-CCP was positive in 26(51%), and anti-CarP in 21 (41.2%) patients. Anti-CarP antibodies were significantly associated with radiological damage, DAS28, HAQ and acute phase reactants. The sensitivity and specificity were 41.2% and 88.6%, respectively for anti-CarP, 51% and 93.2% for anti-CCP and 78.4% and 90.9% for RF to diagnose RA. Conclusions: An association between anti-CarP antibody positivity and the disease activity, severity, structural damage and hence poor disease outcome has been demonstrated. Testing anti-CarP antibodies could be a useful marker for the assessment of disease activity as well as the expectation of prognosis in RA patients.

Objective.Rheumatoid arthritis (RA) is more common in females, and although the cause of RA is unknown, it is characterized by the production of autoantibodies. The aims of this study were to determine whether RA-associated autoantibodies are more often found in females than males and to identify factors that influence the relationship between sex and seropositivity.Methods.Databases were searched and studies of RA (N ≥ 100) were included if they reported proportion of seropositive patients with RA by sex. Metaanalyses and metaregression were conducted using the random-effects model. Covariates regressed were smoking, age, BMI, Health Assessment Questionnaire–Disability Index (HAQ-DI), and the Disease Activity Score in 28 joints (DAS28).Results.Eighty-four studies with a total of 141,381 subjects with rheumatoid factor (RF) seropositivity and 95,749 subjects with anticitrullinated protein antibody (ACPA) seropositivity met inclusion criteria. The mean age of participants ranged from 37 to 68 years and the proportion of female subjects ranged from 9% to 92%. Results indicated that females were less likely than males to be seropositive: odds ratio (OR) 0.84 [95% CI 0.77–0.91] for RF and OR 0.88 [95% CI 0.81–0.95] for ACPA. BMI, smoking, mean age, DAS28, and HAQ-DI did not affect the relationship between sex and seropositivity.Conclusion.Although studies report that females have higher RA disease activity than males and that seropositivity predicts worse outcomes, females were less likely to be seropositive than males.

Rheumatoid factor (RF) binds to the fragment crystallizable (Fc) portion of immunoglobulin. It could bind to the Fc portion of anti-TNF inhibitors (TNFi) and attenuate the clinical efficacy. We tried to determine whether the therapeutic efficacy of TNFi with Fc might be lower than that of TNFi without Fc in rheumatoid arthritis (RA) patients with high titres of RF. The Kansai Consortium for Well-being of Rheumatic Disease Patients (ANSWER) cohort is an observational multi-center registry of patients with RA in the Kansai district of Japan. RA patients treated with TNFi were included and divided into two groups based on the structural characteristics between TNFi with Fc (infliximab, adalimumab, golimumab, and etanercept) and TNFi without Fc (certolizumab pegol). Patients were classified into 4 groups according to RF titre quartiles. The sequential disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) was compared by Mann-Whitney U test between TNFi with and without Fc in each RF titre group. Multiple linear regression analysis was used to analyze the effect of TNFi without Fc for the change of DAS28-ESR adjusted after potential confounders. A total of 705 RA patients were classified into four groups (RF

Patients with established rheumatoid arthritis (RA) demonstrate altered immune responses to Epstein-Barr virus (EBV), but the presence and roles of EBV have not been fully explored during the pre-clinical disease period. This study was undertaken to determine if EBV infection, as evidenced by an altered anti-EBV antibody response, either plays an important role in driving the development of RA or is a result of expanded RA-related autoimmunity.A total of 83 subjects with RA according to the 1987 American College of Rheumatology (ACR) criteria and 83 age-, sex-, and race-matched control subjects without RA were included in our study. We collected sera from RA subjects and matched controls during the pre-RA and post-RA diagnosis periods and tested the sera for the presence of 5 anti-EBV antibodies (anti-EBV nuclear antigen 1 IgG isotype, anti-viral capsid antigen [anti-VCA] isotypes IgG and IgA, and anti-early antigen [EA] isotypes IgG and IgA), 7 RA-related autoantibodies (rheumatoid factor measured by nephelometry [RF-Neph] as well as isotype-specific IgA-RF, IgM-RF, and IgG-RF, and anti-cyclic citrullinated peptide [anti-CCP] antibodies, including anti-CCP2, anti-CCP3, and anti-CCP3.1), 22 cytokines/chemokines, 36 individual anti-citrullinated protein antibodies, and IgG-cytomegalovirus (CMV) antibodies. Random forest classification, mixed modeling, and joint mixed modeling were used to determine differences in anti-EBV antibody levels between RA subjects and controls.Random forest analysis identified the presence of preclinical EBV antibodies in the serum that differentiated RA subjects from controls without RA. Specifically, IgG-EA antibody levels were higher in RA subjects (mean ± SD 0.82 ± 0.72 international standardized ratio [ISR]) compared to controls (mean ± SD 0.49 ± 0.28 ISR). In subjects with RA, elevated serum IgG-EA levels in the preclinical period before seroconversion were significantly correlated with increased serum IgM-RF levels (P = 0.007), whereas this correlation was not seen in control subjects without RA (P = 0.15). IgG-CMV antibody levels did not differ between groups.Subjects whose serum IgG-EA antibody levels are elevated in the preclinical period will eventually develop RA, which suggests that EBV reactivation cycles are increased during the preclinical period of RA. A combination of RF and EBV reactivation may play an important role in the development of RA.

Palindromic rheumatism (PR) is characterized by self-resolving and short duration attacks of arthritis/periarthritis. The present study was performed to report the results of PR treatment with methotrexate (MTX).We reviewed the charts of 152 patients with diagnosis of PR. Inclusion criteria were diagnosis of PR according to the criteria of Weismann, age ≥16, active disease and treatment with MTX for at least 6 months. Disease outcome was assessed by reaching remission and prevention of disease evolution to chronic arthritis. Remission was defined as stopping the attacks for 12 weeks and prednisolone dose ≤5 mg/d. MTX treatment failure was defined as failure to achieve remission, the need to add other disease-modifying antirheumatic drugs and disease progression to chronic arthritis.Fifty-nine patients were included in the study. Median duration of follow-up was 43 months. Attacks were controlled in 89.8% of patients. In 80% of the patients remission occurred during 12 months after starting treatment with MTX. Treatment failed in 20.3% of patients. Wrist joint involvement and positive rheumatoid factor (RF) were significantly more common in the MTX treatment-failed group. In RF positive patients evolution to rheumatoid arthritis was more common than in RF negative patients. No significant differences were observed in remission rate and evolution to rheumatoid arthritis in anticitrullinated C peptide positive and negative patients.The present study, demonstrated the efficacy of MTX in controlling PR in seropositive and seronegative patients over a median of 43 months of treatment.

Erosive Hand OsteoArthritis (EHOA) is a common rheumatological problem. We aim to determine characteristics of EHOA patients: comorbidities, radiographic erosivity and pain experienced after being diagnosed, in order to find which of these are potentially relevant in upcoming interventional trials.Retrospective analysis of EHOA patients within the electronic database in one centre, with a telephone interview on pain as experienced even exceeding 12 months after being diagnosed.Eighty-four non-academic EHOA patients were found: 89% females (median age 69 years), 11% males (similar age distribution). Kellgren-Lawrence (KL) erosivity scores in both sexes were comparable; DIPs scored higher than PIP's. Comorbid conditions were crystal-induced arthritis, rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in 8%, 5% and 1%, respectively; seropositivity for rheumatoid factor and anti-citrullinated protein antibodies in 8% and 1% respectively. Pain worst experienced often exceeded a visual analogue score of 5.0, but was unrelated to the total KL score. Some pain reduction was reached with non-steroidals (perorally/transcutaneously) as deduced from continued use in 1 in 3.In many EHOA patients, there is an unmet need regarding the treatment of pain, which per se was not directly correlated with erosivity score. Future studies may be designed considering the aforementioned characteristics, acting on the inflammatory process resulting in PIP/DIP erosions, with the exclusion of RA and PsA in order to get a clean study on EHOA. Several studies with monoclonal antibodies have been performed but demonstrated ineffectivity on the outcome of pain. Hope glooms with the arrival of innovative small molecules that may reach EHOA target cells. Key Points • Erosive handOA is a common problem in non-academic rheumatology; it is often associated with significant pain in both sexes exceeding a VASpain of 5.0 even years after being diagnosed; 1 in 3 found some relief in non-steroidals perorally/transcutaneously. • Future studies will have to focus on (episodic) inflammatory hand OA resulting in proven erosivity (EHOA) located in PIP plus DIP joints and may have to exclude comorbid active crystal-induced arthritis as well as rheumatoid/psoriatic arthritis and possibly even RF/ACPA seropositivity in order to get a clean study on EHOA. • As several big monoclonals have failed in EHOA, we may have to search for promising new drugs within the group of small molecules. These will have to show a significant pain-reducing effect and preferably also a disease-modifying osteoarthritis drug (DMOAD) effect.

Background. Rheumatoid arthritis (RA) belongs to the most common inflammatory diseases of the joints, and in its pathogenetic constructions, a certain role is played by the changes in the autonomic nervous system (ANS). Aim of the study: to evaluate the vegetative passport in RA, the incidence and nature of vegetative dysfunction (VD) in different types of the disease, the relationship with the parameters of variation pulsometry. Materials and methods. There were examined 173 patients with RA aged 18 to 79 years (an average of 46 years), among them there were 21 % of males and 79 % of females. The duration of the disease was 10 years, type of RA, seropositive in terms of rheumatoid factor and citrulline antibodies, was detected in 3/4 of cases, extra-articular (systemic) form of the disease was diagnosed in 37 % of observations, osteoporosis was found in 67 % of patients. Results. VD is observed in 20 % of RA patients, mainly in those with seropositive variant of the disease that is associated with higher values of bone mineral density, larger changes in the variation pulsometry, with the influence on the integral nature of articular syndrome and the rate of involvement in the pathological process of elbow and hip joints, and the severity of autonomic disorders is closely linked to the presence of intra-articular arthrocalcifications, digital arteritis and dyscirculatory encephalopathy. Vegetative passport defines the integral clinical and laboratory and instrumental RA symptoms, while the ANS type is affected by the seropositivity of the disease and the bone density, with the highest level in cases of vagotonia, when VD directly correlates with the joint pathology progression rate, and in sympathicotonia — with intial parameters of rheumatoid factor and arthritis activity, also, regardless of the vegetative status, there are variance-correlation ratios of specific parameters of RA course and variation pulsometry. Conclusions. VD occurs in every fifth patient with RA, is associated with the peculiarities of the articular syndrome course and extra-articular signs of the pathological processes, is involved in disease pathogenesis constructions, and in the future it will be useful to identify actively ANS changes for subsequent timely rehabilitation.

Relevance. Rheumatoid arthritis (RA) belongs to the most common inflammatory diseases of the joints, and the number of patients with this pathology increases everywhere, causing enormous medical, social and economic damage. An important role in the pathogenesis of RA is given to dysfunctions of the autonomic neural system (ANS), which condition is closely related to the bone metabolism and bone mineral density. The purpose and objectives: to assess the incidence of osteoporosis at different «vegetative passport» of RA patients, to explore the relationship of vegetative dysfunction (VD) signs with the nature of bone density. Material and methods. There were examined 173 patients with RA aged 18 to 79 years (average age — 46 years), among them 21 % males and 79 % females. The duration of disease manifestations was 10 years, variation of RA, seropositive for rheumatoid factor and citrulline antibodies, was detected in 3/4 of cases, extraarticular (systemic) form of the disease was diagnosed in 37 % of cases. Results. Osteoporosis develops in 2/3 of RA patients, and its pathogenic constructions are closely associated with the presence of VD, the severity of which is correlated with indicators of bone density, and those, in turn, — with parameters of variation pulsometry, activity and bone-destructive components of articular syndrome, depends on the vegetative type of patients (vagotonia is more typical for patients with osteoporosis, and for the rest of the patients — sympathotony). The imbalance of bone metabolism markers in RA patients enhances the existing violations of ANS, and the content of magnesemia has prognostic value in relation to VD. Its severity correlates with the severity of osteoporosis, wherein unfavorable prognostic indicators are blood calcium level more than 80 mg/l and alkaline phosphatase activity over 180 U/l. Conclusion. The development of osteoporosis is associated not only with features of the articular syndrome course and extraarticular RA symptoms, but also with the state of the ANS, which is involved in the pathogenetic constructions of bone density reduction and imbalance of bone metabolism markers. In the future, the active identification of VD will be useful for subsequent timely rehabilitation.

Aim of the work To evaluate the demographic, clinical presentation, and laboratory findings of the juvenile idiopathic arthritis (JIA) subtypes in Sudanese patients attending the Pediatric Rheumatology Clinic. Patients and methods This single-center study was conducted at the Rheumatology Clinic of Ahmed Gasim Hospital, Khartoum North. A specially designed data collection form was used. Full medical history and physical examination of patients was done. The initial investigation was collected from the patients' records. Results Eighty-one patients were enrolled in the study. Females were 54 and 27 males (F: M was 2:1). The mean age of the patients was 10.8 ± 3.6 years, 58% were above 10 years; disease duration 5.8 ± 2.4 years and age at onset 9 ± 3.8 years, the commonest age at onset was between 5 and 10 years. Half of the patients were from rural areas. There was a positive family history in 7.4%. Morning stiffness was the commonest presenting symptom (98.8%) and uveitis was present in 8.6%. The knee was the most affected joint (82.7%). The polyarticular subtype was found in 51 (63%), systemic-onset in 18 (22.2%), oligo articular in 10 (12.3%) and spondyloarthritis in 2 (2.5%). Seven patients (8.6%) had uveitis. Rheumatoid factor (RF) and antinuclear antibody (ANA) were positive among 30.9% and 46.9% of the participants respectively. Conclusion Females predominate and half of the patients are from rural areas. Polyarticular is the commonest subtype. Morning stiffness is the presenting symptom. The knee joint was the most affected. Positive RF was found in one-third of patients, ANA in about half of them.

Aim of the work To analyze the relationship between miRNA-146a rs2910164 and rheumatoid arthritis (RA) susceptibility and clarifying its association with disease activity and extra-articular involvement. Patients and methods The study enrolled 50 RA patients and 40 controls. DNA extraction from whole blood was done. Genotyping was performed by real-time polymerase chain reaction. The selected single nucleotide polymorphism was rs2910164 in the miRNA-146a gene. Genotyping was performed on genomic DNA samples by allelic discrimination assay. Disease activity score (DAS28) and health assessment questionnaire-disability index (HAQ-DI) were assessed. Results The mean age of patients was 44.8 ± 9.9 years while age at onset was 37.2 ± 9.8 years. Female:male was 5.3 vs 1. Females had significantly higher DAS28, visual analogue scale and rheumatoid factor (RF) than males (p = 0.04, p = 0.009, p = 0.03). The frequency of GC genotype was more in both males and females (62.5 vs 47.6%). GC genotype and G allele were the most frequent in patients. No significant difference in the frequency distribution of genotypes and alleles was observed between patients and controls. There was a significant difference in the number of swollen joints (p = 0.04) and sicca symptoms (p = 0.01) being higher in those with CC genotype with a tendency of increased DAS28, HAQ-DI, deformities and rheumatoid nodules with CC genotype and interstitial pulmonary fibrosis and RF with GG genotype. Conclusions CC genotype was associated with sicca symptoms and swollen joints, deformities, disease activity and functional disability. miRNA-146a may be a potential biomarker for extra-articular manifestations of RA that need more attention and warrant aggressive therapy.

ObjectivesThe human leukocyte antigen-shared epitope (HLA-SE) alleles and smoking are the most prominent genetic and environmental risk factors for rheumatoid arthritis (RA). However, at which pre-arthritis stage (asymptomatic/symptomatic) they exert their effect is unknown. We aimed to determine whether HLA-SE and smoking are involved in the onset of autoantibody positivity, symptoms (clinically suspect arthralgia (CSA)) and/or progression to clinical arthritis.MethodsWe performed meta-analyses on results from the literature on associations of HLA-SE and smoking with anti-citrullinated protein antibodies (ACPAs) in the asymptomatic population. Next, we studied associations of HLA-SE and smoking with autoantibody positivity at CSA onset and with progression to clinical inflammatory arthritis (IA) during follow-up. Associations in ACPA-positive patients with CSA were validated in meta-analyses with other arthralgia cohorts. Analyses were repeated for rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and anti-acetylated protein antibodies (AAPA).ResultsMeta-analyses showed that HLA-SE is not associated with ACPA positivity in the asymptomatic population (OR 1.06 (95% CI:0.69 to 1.64)), whereas smoking was associated (OR 1.37 (95% CI: 1.15 to 1.63)). At CSA onset, both HLA-SE and smoking associated with ACPA positivity (OR 2.08 (95% CI: 1.24 to 3.49), OR 2.41 (95% CI: 1.31 to 4.43)). During follow-up, HLA-SE associated with IA development (HR 1.86 (95% CI: 1.23 to 2.82)), in contrast to smoking. This was confirmed in meta-analyses in ACPA-positive arthralgia (HR 1.52 (95% CI: 1.08 to 2.15)). HLA-SE and smoking were not associated with RF, anti-CarP or AAPA-positivity at CSA onset. Longitudinally, AAPA associated with IA development independent from ACPA and RF (HR 1.79 (95% CI: 1.02 to 3.16)), anti-CarP did not.ConclusionsHLA-SE and smoking act at different stages: smoking confers risk for ACPA and symptom development, whereas HLA-SE mediates symptom and IA development. These data enhance the understanding of the timing of the key risk factors in the development of RA.

ObjectiveRheumatoid arthritis (RA) is often complicated with chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway disease, which occur as extra-articular manifestations. CLD in RA have been associated with the production of rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), or anti-carbamylated protein (CarP) antibody. However, few validation studies have been performed thus far. In the present study, we investigated the association of RF, ACPA, and anti-CarP antibodies with RA complicated with CLD.MethodsSera from RA patients with or without CLD were collected. The levels of serum RF, RF immunoglobulin A (IgA), ACPA IgG, ACPA IgA, and ACPA secretory component (SC) were measured using enzyme-linked immunosorbent assay.ResultsThe comparison of RA patients with and without CLD showed that RF IgA was associated with ILD (mean ± standard deviation: 206.6 ± 400.5 vs. 95.0 ± 523.1 U/ml, respectively,P = 1.13 × 10− 8), particularly usual interstitial pneumonia (UIP) (263.5 ± 502.0 U/ml,P = 1.00 × 10− 7). ACPA SC was associated with RA complicated with ILD (mean ± standard deviation: 8.6 ± 25.1 vs. 2.3 ± 3.4 U/ml, respectively,P = 0.0003), particularly nonspecific interstitial pneumonia (NSIP) (10.7 ± 31.5 U/ml,P = 0.0017). Anti-CarP antibodies were associated with RA complicated with ILD (0.042 ± 0.285 vs. 0.003 ± 0.011 U/ml, respectively,P = 1.04X10− 11).ConclusionRF IgA and ACPA SC in RA were associated with UIP and NSIP, respectively, suggesting different specificities in patients with RA. Anti-CarP antibodies were associated with ILD in RA. These results may help elucidate the different pathogeneses of UIP and NSIP in RA.

In this thesis two main aims were addressed. It has long been established that early treatment of rheumatoid arthritis (RA) improves disease outcomes. In Part I of this thesis we therefore further investigated the early detection of at-risk individuals by studying a large cohort of patients with clinically suspect arthralgia (CSA). We explored the value of two easy clinical tests, their potential to detect underlying inflammatory processes and to predict disease progression. In addition we investigated the presence of subclinical synovitis on imaging as starting point for treatment with disease modifying anti-rheumatic drugs (DMARDs) and the value of magnetic resonance imaging (MRI) detected erosions as new predictor for RA-development. In Part II of this thesis we aimed to determine which disease processes are involved in the different phases of RA-development. Knowledge on disease pathogenesis and timing of influencing factors can help to better target treatment during RA-development. We therefore evaluated whether autoantibody-response maturation occurred during the phase of CSA, and investigated the timing of genetic risk factor human leukocyte antigen-shared epitope (HLA-SE) and environmental risk factor smoking during the development of autoantibody-positive disease.

Objective: The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks. Method: We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland. A rheumatologist reviewed the medical records to assess whether each patients’ diagnosis was correct. The diagnosis was compared with the diagnostic codes in the Finnish Care Register for Health Care (CRHC) and special reimbursement data of the Social Insurance Institution of Finland. Results: The positive predictive value (PPV) of CRHC diagnosis of RA (for seropositive and seronegative RA combined) was 0.82. For patients with a special reimbursement for anti-rheumatic medications for RA, the PPV was 0.89. The PPV was higher in patients with more than one visit. For one, two, five, and 10 visits, the PPV was 0.82, 0.85, 0.89, and 0.90, respectively, and for patients who also had the special reimbursement, the PPV was 0.89, 0.91, 0.93, and 0.94 for one, two, five, and 10 visits, respectively. In patients positive for anti-citrullinated protein antibodies, the PPV was 0.98. Conclusion: These results demonstrate that the validity of RA diagnoses in Finnish biobanks was good and can be further improved by including data on special reimbursement for medication, number of visits, and serological data. publishedVersion

Hintergrund: Autoantikörper gegen das native und citrullinierte heterogene nukleäre Ribonukleoprotein-D-like (hnRNP-DL; JKTBP) wurden bei Patienten mit systemischem Lupus erythematodes (SLE) und rheumatoider Arthritis (RA) und im Tiermodell analysiert. Genetische, klinische und diagnostische Aspekte bei der RA wurden analysiert und die autoantigenen Strukturen sowie posttranslationalen Modifikationen charakterisiert, über die gegebenenfalls ein krankheitsspezifischer Nachweis erfolgen kann, um RA-Risikopersonen zu identifizieren sowie Behandlungserfolg und -möglichkeiten aufzuzeigen. Methoden: Durch Protein-Makroarray Untersuchungen konnten α-hnRNP-DL-Autoantikörper spezifisch bei RA-Patienten identifiziert werden. Rekombinante, in E. coli exprimierte, hnRNP-DL-Proteine wurden in der ELISA-Technik verwendet und α-hnRNP-DL-Autoantikörper im Serum von SLE- und RA-Patienten sowie von Mäusen aus Tiermodellen gemessen. Die hnRNP-DL-Expression wurde durch indirekte Immunfluoreszenz, Immunoblot und Immunhistochemie in Synovialgewebe sowie in kultivierten Zellen analysiert. Ergebnisse: HnRNP-DL wurde als native oder citrullinierte Proteinvariante von Autoantikörpern von Patientenuntergruppen mit unterschiedlichem RA-Status erkannt. Bei SLE-Patienten wurden bei 58 % Seroreaktionen gegen strukturelle citrullinierungsabhängige Epitope (SCEs) von hnRNP-DL nachgewiesen, obwohl 98 % dieser Seren im Routinetest auf α-CCP2-Ak negativ waren. Zur Erkennung von RF-IgM/α-CCP2-seronegativen Früh-RA-Patienten (24-46 %) und als Wert zur Einschätzung des Behandlungserfolgs wurde der „Citrullinated-Native-hnRNP-DL-Index“ (CNDL-Index) als Differenzwert von α-cit-hnRNP-DL- und α-hnRNP-DL-OD-Signalen eingeführt. Hohe positive CNDL-Werte korrelierten mit einem schwereren RA-Verlauf, dem Vorliegen von „shared-epitope“-Allelen und parenchymatösen Lungenveränderungen. Speziell bei SLE-Patienten, bei RA-Risikopersonen und bei den frühen RA-Kohorten wie EIRA wurde häufiger ein negativer CNDL-Index festgestellt und bei den EIRA-Patienten häufiger in der Gruppe, die auf Methotrexat (MTX)-Therapie ansprachen (87 %). Höhere native α-hnRNP-DL-Werte wurden mit geringeren Schmerzen assoziiert und speziell bei seronegativen RA-Patienten mit MTX- oder Etanercept-Therapieansprechen assoziiert. Im SLE-Mausmodell MRL/lpr zeigten die Ergebnisse, dass die Bildung von α-hnRNP-DL Autoantikörpern Toll-like-Rezeptor (TLR) 7- und TLR9-abhängig ist und durch Zytokine (Interleukin-1α/-6, Tumor-Nekrose-Faktor-α) reguliert wird. Bei der Immunfluoreszenz färbten die α-hnRNP-DL-Autoantikörper spezifisch Stressgranula im Zytoplasma an. Immunhistochemische Analysen weisen auf eine zytoplasmatische Expression verstärkt im Grenzbereich von RA-Synovialgewebe hin, nicht aber bei Arthrose und normalem Kontrollgewebe und legen nahe, dass hnRNP-DL im rheumatoiden Gelenk citrulliniert ist. Schlussfolgerungen: HnRNP-DL ist ein neues Autoantigen bei RA- und SLE-Patienten. Es wird auch in Mausmodellen für entzündliche rheumatische Erkrankungen als Autoantigen erkannt. Anti-hnRNP-DL-Autoantikörper sind für die Differentialdiagnose der RA bedeutsam und zeigen einen prognostischen Wert für das therapeutische Ansprechen, vor allem in frühen Krankheitsstadien. Die Citrullinierung von hnRNP-DL führt zu Strukturepitopen (SCEs), die auch von α-CCP2-negativen SLE-Patienten erkannt werden. Durch kombinierte Betrachtung des nativen und citrullinierten Antigens, mittels CNDL-Index, wurde die serodiagnostische RA-Früherkennung deutlich verbessert und ein Prädiktivparameter für das Therapieansprechen mit MTX oder Etanercept identifiziert., Background: Autoantibodies against native and citrullinated heterogeneous nuclear ribonucleoprotein D-like (hnRNP-DL; JKTBP) were analyzed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and in animal models. Genetic, clinical and diagnostic aspects in RA were analyzed and the autoantigenic structures and post-translational modifications were characterized, which might be used for disease-specific detection to identify SLE-patients, RA-risk-individuals and therapy-success and -options. Methods: Protein macroarray studies identified α-hnRNP-DL-autoantibodies specifically in RA patients. Recombinant hnRNP-DL proteins expressed in E. coli were used in ELISA-technique to measure α-hnRNP-DL autoantibodies in serum of SLE-, RA-patients and mouse models. The hnRNP-DL expression was analyzed by indirect immunofluorescence, immunoblot and immunohistochemistry in synovial tissue and cultured cells. Results: HnRNP-DL was detected as native or citrullinated protein variant of autoantibodies from patient-subgroups with different RA-status. In SLE-patients, seroreactions against structural citrullination-dependent-epitopes (SCEs) of hnRNP-DL were detected in 58 %, although 98 % of these sera were negative for α-CCP2 routine assay. To detect RF-IgM/α-CCP2-seronegative early RA-patients (24-46 %) and as a value to assess treatment success the "Citrullinated-Native-hnRNP-DL-index" (CNDL-index), as a difference value of α-cit-hnRNP-DL and α-hnRNP-DL OD-signals, was introduced. High positive CNDL-values correlated with a more severe RA-course, the presence of "shared-epitope" alleles and parenchymal lung changes. Specifically in SLE-patients, RA-at-risk-individuals, and early RA-cohorts such as EIRA a negative CNDL-index was observed and more frequently in the EIRA-patients subgroup, responding to methotrexate (MTX) therapy (87 %). Higher native α-hnRNP-DL values were associated with lower pain and specifically in seronegative RA-patients, with MTX- or etanercept-therapy response. In the SLE-mouse-model MRL/lpr, results showed that α-hnRNP-DL autoantibody formation is Toll-like-receptor (TLR) 7- and TLR9-dependent and regulated by cytokines (interleukin-1α/-6, tumor-necrosis-factor-α). In immunofluorescence, the α-hnRNP-DL autoantibodies specifically stained stress granules in the cytoplasm. Immunohistochemical studies indicate cytoplasmic expression, enhanced in the peripheral region of RA synovial tissue, while not in osteoarthritis and normal control tissue, suggesting that hnRNP-DL is citrullinated in the rheumatoid joint. Conclusions: HnRNP-DL is a novel autoantigen in RA- and SLE-patients. It is also recognized as an autoantigen in mouse-models of inflammatory rheumatic diseases. Anti-hnRNP-DL-autoantibodies are significant for the differential diagnosis of RA and demonstrate prognostic value for therapeutic response, especially in early stages of disease. Citrullination of hnRNP-DL results in SCEs, that are also recognized by α-CCP2-negative SLE-patients. Combined analysis of native and citrullinated antigen using the CNDL-index, significantly improved serodiagnostic early RA-detection and provided a predictive parameter for treatment response with MTX or etanercept.

To describe the clinical spectrum of Sjögren's syndrome (SS) patients with combined seronegativity.From a multicentre study population of consecutive SS patients fulfilling the 2016 ACR-EULAR classification criteria, patients with triple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(+)] and quadruple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(-)] were identified retrospectively. Both groups were matched in an 1:1 ratio with 2 distinct control SS groups: i) classic anti-Ro/SSA seropositive patients [SS(+)] and ii) classic anti-Ro/SSA seropositive patients with negative rheumatoid factor [SS(+)/RF(-)] to explore their effect on disease expression. Clinical, laboratory and, histologic features were compared. A comparison between triple and quadruple seronegative SS patients was also performed.One hundred thirty-five SS patients (8.6%) were identified as triple seronegative patients and 72 (4.5%) as quadruple. Triple seronegative patients had lower frequency of peripheral nervous involvement (0% vs. 7.2% p=0.002) compared to SS(+) controls and lower frequency of interstitial renal disease and higher prevalence of dry mouth than SS(+)/RF(-) controls. Quadruple seronegative patients presented less frequently with persistent lymphadenopathy (1.5% vs. 16.9 p=0.004) and lymphoma (0% vs. 9.8% p=0.006) compared to SS(+) controls and with lower prevalence of persistent lymphadenopathy (1.5% vs. 15.3% p=0.008) and higher frequency of dry eyes (98.6% vs. 87.5% p=0.01) and autoimmune thyroiditis (44.1% vs. 17.1% p=0.02) compared to SS(+)/RF(-) SS controls. Study groups comparative analysis revealed that triple seronegative patients had higher frequency of persistent lymphadenopathy and lymphoma, higher focus score and later age of SS diagnosis compared to quadruple seronegative patients.Combined seronegativity accounts for almost 9% of total SS population and is associated with a milder clinical phenotype, partly attributed to the absence of rheumatoid factor.

Post Translational Modification (PTM) is a process in which covalent addition of functional groups on protein occurs to maintain their structure, function and stability. Every PTM process in our living system occurs to enhance the functional diversity of a protein. But sometimes, it occurs without any regulation and that might lead to autoimmunity. Rheumatoid arthritis (RA) is one such chronic, inflammatory, autoimmune disease that affects the joints. Proper treatment can make the symptoms manageable for RA, but it is not curable. Delayed diagnosis of RA can cause severe bone pain, stiffness, inflammation, redness in joints and affect other parts of the body such as the liver, kidney, etc. Early diagnosis of RA is necessary to manage the aggressive symptoms. Currently, Rheumatoid factor (RF) and anti-citrullinated cyclic peptide (Anti-CCP) are considered as biomarkers to diagnose RA. Besides citrullination, several other PTMs are also involved in the generation of autoantibodies, such as carbamylation, glycosylation, glycation, acetylation, ubiquitination, proteolysis, phosphorylation, and lipidation. The aim of this review is to elucidate several changes in the form, nature, and function of PTMs in RA. This review will give a recent overview on the role of PTMs in the pathogenesis of RA with a focus on the post-translational modifications.

Objectives To evaluate the effect of corticosteroid injections in the painful temporomandibular joint (TMJ) of patients with rheumatoid arthritis (RA) in relation to systemic inflammatory activity. Method Examination of 35 patients (median age 54 years; 89% female) included maximum mouth opening capacity, degree of anterior open bite (AOB), TMJ pain intensity at rest, and crepitus. Serum levels of rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serotonin, and plasma levels of interleukine-1β (IL-1β) were determined. Out of the 70 examined joints, 53 joints received a corticosteroid (methylprednisolone) injection after the clinical examination at baseline (T0). The examination was repeated for all patients at T1 (median 3.1 weeks after T0), and for 21 patients at T2 (median 6.3 weeks after T1), of whom 20 patients received a second injection at T1. Results Maximum mouth opening capacity significantly increased, and TMJ pain intensity significantly decreased between T0 and T1, but these improvements were no longer present at T2. No differences were found in AOB between the time points. Of the joints that received an injection at T0, 19 joints had pretreatment crepitus, which resolved in eight joints at T1. No correlations were found between the change in mouth opening capacity or TMJ pain intensity and ESR, CRP, serotonin, or IL-1β. Conclusions Methylprednisolone injections in the TMJ alleviate pain and improve mouth opening capacity for approximately 3 weeks, allowing patients to perform jaw exercises during this timeframe of temporary relief. It thus seems useful for the short-term management of TMJ involvement in RA. Key Points• In rheumatoid arthritis, corticosteroid injection in the temporomandibular joint alleviates pain and improves function.• The clinical improvement achieved with methylprednisolone injections lasts for approximately 3 weeks.• Corticosteroid injections could be used to facilitate and support additional noninvasive, conservative treatment options.

BackgroundPredicting progression to clinical arthritis in individuals at-risk of developing rheumatoid arthritis is a prerequisite to developing stratification groups for prevention strategies. Selecting accurate predictive criteria is the critical step to define the population at-risk. While positivity for anti-citrullinated protein antibodies (ACPA) remains the main recruitment biomarker, positivity for other autoantibodies (AutoAbs) identified before the onset of symptoms, may provide additional predictive accuracy for stratification.ObjectiveTo perform a multiple AutoAbs analysis for both the prediction and the time of progression to inflammatory arthritis (IA).Methods392 individuals were recruited based on a new musculoskeletal complaint and positivity for ACPA or rheumatoid factor (RF). ELISAs were performed for ACPA, RF, anti-nuclear Ab, anti-carbamylated protein (anti-CarP) and anti-collagen AutoAbs. Logistic and COX regression were used for analysis.ResultsProgression to IA was observed in 125/392 (32%) of cases, of which 78 progressed within 12 months. The AutoAbs ACPA, RF, anti-CarP were individually associated with progression (p77%; area under the curve (AUC) >0.789), compared with prediction using only demographic/clinical data (72.9%, AUC=0.760). Multiple AutoAbs testing provided added value, with +6.4% accuracy for number of positive AutoAbs (AUC=0.852); +5.4% accuracy for AutoAbs levels (ACPA/anti-CarP, AUC=0.832); and +6.2% accuracy for risk-groups based on high/low levels (ACPA/RF/anti-CarP, AUC=0.837). Time to imminent progression was best predicted using ACPA/anti-CarP levels (AUC=0.779), while the number of positive AutoAbs was/status/risk were as good (AUC=0.778).ConclusionWe confirm added value of multiple AutoAbs testing for identifying progressors to clinical disease, allowing more specific stratification for intervention studies.

Objectives Whether the characteristics of patients with rheumatoid arthritis (RA) undergoing total knee arthroplasty (TKA) have changed in the era of biologic disease-modifying antirheumatic drugs (bDMARDs) is unclear. We compared the radiographic findings of the knees in TKA recipients with RA before and after the introduction of bDMARDs. Methods Consecutive patients who underwent primary TKA between 1999 and 2002 (115 knees; 79 patients, group A) and between 2013 and 2017 (117 knees; 95 patients, group B) were retrospectively evaluated. Clinical data, including disease duration, medication, C-reactive protein, erythrocyte sedimentation rate, and rheumatoid factor, were collected. The Larsen classification, joint space narrowing (JSN), bone erosion, and geode and osteophyte formation were evaluated on preoperative radiographs. Results Osteophyte formation was significantly increased, and bone erosion and geode formation were significantly decreased in group B. In addition, medial-dominant JSN was significantly increased, and bicompartmental JSN was significantly decreased in group B. Medial-dominant JSN was positively and bone erosion was negatively associated with osteophyte formation. Conclusions Following the introduction of bDMARDs, typical radiographic findings of rheumatoid knees have decreased, and secondary osteoarthritis-like changes, characterized by osteophyte formation and medial-dominant JSN, have increased in the knees of TKA recipients.

PURPOSE Beneficial effect of long-chain ω-3 fatty acids against symptoms of rheumatoid arthritis (RA) has been indicated in previous studies. We examined the effect of flaxseed and anti-inflammatory diet in patients with RA. METHODS The 12-week intervention was performed on 120 patients with RA who were randomized to three groups of flaxseed (30 g/day) plus anti-inflammatory diet (AIF group), flaxseed (30 g/day) plus regular diet (RF group), and roasted wheat (30 g/day) plus regular diet (RW group). Disease Activity Score 28-joints (DAS28), health assessment questionnaire (HAQ) disability and pain, quality of life, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, and anti-cyclic citrullinated peptides (anti-CCP) were measured before and after trial. Analysis was performed using per-protocol and intention-to-treat (ITT) approaches. RESULTS One hundred and two patients completed the protocol. Flaxseed decreased DAS28 in RF group compared to RW (- 0.87 ± 1.11 vs. - 0.24 ± 0.78; P = 0.014). Pain severity (P ≤ 0.001), morning stiffness (P

Background: Rheumatoid Arthritis (RA) is a chronic inflammatory disorder that impact daily life activities. The impact on work productivity is critical because of persistent work disability. Aim: To evaluate work productivity in RA patients compared to healthy controls, and to assess the impact of socio-demographic characteristics on work productivity. Methods: This was a case-control study conducted at the Rheumatology Unit of Baghdad Teaching Hospital, Medical City during the period from August 2020 to the end of March 2021. Seventy-two patients with RA were selected and compared with 72 healthy subjects as a control group. All patients were diagnosed according to ACR/EULAR 2010 RA classification criteria. The socio-demographic and clinical features, lifestyle practices, and disease activity of the patients and controls were all recorded during interviews. A standardized Arabic version of the Workplace Activity Limitation Scale (WALS) and the Job Limitations Questionnaire were used to assess the impact of RA on work productivity (WLQ-25). Results: The vast majority of patients were females (58.1%). Positive rheumatoid factor was reported in 94.4% of the patients. The patients showed a significantly lower WALS total score and higher WLQ-25 total score median (IQR) compared with controls. Conclusion: Active RA impairs the work productivity which was influenced by CDAI score and negatively associated with the use of DMARDs.

Background: Rheumatoid arthritis is the most common cause of inflammatory polyarthritis. Interleukin‐37 (IL-37) has been found to play an important regulatory role in the development of inflammatory diseases. Objectives: To assess serum IL-37 level in rheumatoid arthritis (RA) patients compared to controls, to evaluate its diagnostic and predictive utility in RA patients and to investigate IL-37 level correlation with demographic and clinical characteristics of RA. Methods: Eighty subjects, 40 RA patients aged between 23-63 years and 40 healthy controls aged between 28-67 years were evaluated. An enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum IL-37 levels. Results: Serum IL-37 was significantly higher in RA patients compared to healthy controls. At optimum cut off value of >58.275 pg/ml, serum IL-37 had 100% accuracy, positive predictive value, negative predictive value, sensitivity, and specificity. Serum IL‐37 level was not significantly related to Disease Activity Score of 28 joints‐erythrocyte sedimentation rate (DAS28‐ESR), also not correlated with C-reactive protein(CRP), rheumatoid factor(RF) and anti-cyclic citrullinated peptide antibody (Anti-CCP). Also there was no correlation between the level of IL-37 and treatment. Conclusions: IL-37 was significantly higher in RA patients compared to healthy controls with a high diagnostic and predictive ability, and may be a potential biomarker for diagnosis and prediction of RA.

Rheumatoid Arthritis or RA disease is a chronic inflammatory and systemic disease associated with broad synovitis resulting in erosion of the articular cartilage and marginal bone causing joint damage. RA is an autoimmune disease with the discovery of an autoantibody, namely rheumatoid factor. The relevant antibody is anti-citrullinated protein (ACPA) antibody. Citullination on the introduction of several proteins such as fibrin, vimentin, fibronectin, collagen type II, which is expressed in the synovial membrane during inflammation by ACPA. In a recent study increased HDAC activity in the synovial tissue of RA patients has increased. Histone deacetylase or abbreviated as HDAC is an enzyme that is important in regulating gene transcription by altering the acetylation of histone proteins which results in an important regulation of repression in the implementation of inflammation. HDAC enzyme inhibitor (HDACi) is an HDAC enzyme inhibitor that can provide benefits for the treatment of various diseases including malignancy and inflammation. In inflammatory disease HDACi overcomes inflammatory cytokines such as TNF-α, IL-6 and IL-1β. One of the HDAC classes is HDAC1 which is highly expressed in the synovial fibroblasts of RA patients. HDACi can burden swollen joints, reduce mononuclear cell infiltration, request pannus orders, inhibit bone and cartilage damage.

The article presents modern ideas about etiology, hereditary predisposition, immunopathogenesis of juvenile rheumatoid arthritis (JRA), one of the most frequent and most disabling rheumatic diseases in children. The etiology of the disease isn’t finally determined. There are only a number of more or less well-founded hypotheses. Among the predisposing factors, an important role belongs to persistent viruses. Arthrotropic persistent viruses — Coxsackie, Epstein-Barr virus, cytomegalovirus, herpes, parvoviruses which have tropism to the joint tissues, can persist for a long time in them, and cause immune inflammation on the background of immunological defects. There is also evidence of a link between JRA and infection caused by Mycoplasma pneumoniae and Chlamydophila pneumoniae. Genetic predisposition and the features of the immune system play a role in the emergence and development of JRA. There is information about the association of HLA histocompatibility genes with JRA in general and with specific variants of the disease. HLA A2, DR5, DR8 are markers of oligoarthritis in girls with uveitis, with seropositivity in antinuclear factor. HLA B27 is a risk marker for JRA developing in boys with oligoarthritis or localized polyarthritis, with predominant lesion of the lower limb joints, with the presence of enthesopathies in school age or adolescence. HLA DR4, DR5, DRB1-04 are markers of JRA in girls with lesions of small symmetrical joints of the hands, seropositive for rheumatoid factor, with the onset of the disease in the senior school age. The defects of T- and B-cell immune are the basis of the pathogenesis of JRA reactions leading to hyperproduction of proinflammatory cytokines. Hyperproduction of proinflammatory cytokines underlies the damage to the synovial membrane of the joint, cartilage, as well as the development of systemic manifestations of the disease. Among a large number of proinflammatory cytokines, the tumor necrosis factor a (TNF-a), interleukins (IL) — 6, 1β, play a key role in the development of the disease. TNF-a leads to chronic inflammation, destruction of the cartilage and bone. IL-6 has an exceptional role in the genesis of the systemic variant of the disease. With its hyperproduction, such extraarticular manifestations of the disease as fever, hypochromic anemia, thrombocytosis are associated. IL-6 stimulates the production of acute-phase proteins by hepatocytes, plays a role in the development of a number of complications, such as osteoporosis and amyloidosis. The state of the cytokine network under various variants of the JRA is not fully studied. Some authors point to the maximum increase in IL-6 and IL-1 in the systemic variant of the disease. A significant increase in TNF-α was detected in patients with polyarticular JRA, especially with high rheumatoid factor values. The level of proinflammatory cytokines correlates with inflammation activity and reflects the severity of the disease, determines a further prognosis. In the development of rheumatic diseases in children, an important role is played not by the absolute amount of certain cytokines, but by the imba-lance of pro- and anti-inflammatory cytokines. This imbalance can arise under the influence of damaging factor: bacterial or viral infection, hypothermia, insolation, preventive vaccinations, joint trauma, adverse environmental factors, chronic psychoemotional stresses. But in most children, after the elimination of damaging factor, the normal ratio of cytokines is restored, and in children with genetic predisposition, the imbalance persists that leads to the development of rheumatic pathology.

Background. The prevalence of rheumatoid arthritis (RA) among the world’s population is about 1 %, and among certain populations of people it reaches 5–7 %. The risk factors for the development and high rates of RA progression include high concentrations of quartz (silicon (Si) dioxide) in the inhaled air, the toxic effect of which is considered as one of the most powerful pathogenetic factors of this disease. The purpose of the work was to evaluate the clinical and pathogenetic significance of silicon microelementosis in RA. Materials and methods. Eighty-three patients with RA were examined (22 % were males and 78 % — females aged from 22 to 75 (mean of 45) years). The duration of the disease from the first signs of its manifestation was 9 years. Systemic form of the disease was diagnosed in 19 % of cases, RA seropositive for rheumatoid factor was detected in 68 %, for cyclic citrullinated peptide antibodies — in 80 % of individuals. The content of Si in the blood serum and in 19 patients — in cerebrospinal fluid was determined using an atomic absorption spectrometer SolAAr-Mk2-MOZe with an electrographite atomizer (Great Bri­tain). Using a computer tensiometer PAT2-Sinterface (Germany), the parameters of the surface tension of blood serum and synovial fluid were investigated with a surface life time of 0.01 sec and tending to infinity, and their ratio was calculated. Results. RA is accompanied by the absence of probable changes in the level of silicon. Si microelementosis is associated with the clinical, radiographic and sonographic signs of the disease course, the degree of activity and severity of arthritis, and silicon imbalance is involved in the pathogenesis of the articular syndrome, damage to the ske­letal muscle, the peripheral nervous system, wherein, Si indicators in blood may have prognostic significance.

Introduction: Chikungunya virus infection (CKV) may lead to chronic arthritis in up to 40% of the patients. There are previous data regarding positive autoantibodies in CKV. Objective: To systematically evaluate the presence of autoantibodies in CKV patients. Methods: All study participants had clinical manifestations and positivity for at least serology or RT-PCR for CKV. The following autoantibodies were performed: antinuclear antibodies (ANA), anti-dsDNA, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti-U1RNP, IgG and IgM anticardiolipin, anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), anti-ribosomal P, lupus anticoagulant, anti-Jo-1 and anti-Scl-70. CH100, C3 and C4 complement components, serum levels of immunoglobulins, C-reactive protein, erythrocyte sedimentation rate, alpha1-acid glycoprotein, anti-thyroglobulin, anti-thyroperoxidase, TRAb , 25 hydroxyvitamin D (25OHD), dengue and zika IgG and IgM antibodies were also measured. Results: 30 CKV patients were included. Mean age was 59.1±15.7 years, 85% female and 77% Caucasian. Disease duration was 4.9±4.0 months. Oligoarthritis was observed in 93%. Mean C-reactive protein levels were 10.1±6.8ng/dL, erythrocyte sedimentation rate 34.2±19.9 mm/1 st hour and alpha1-acid glycoprotein 115.5±52.6 mg/dL. Intramuscular betamethasone depot injection in a single dose was administered in 54%, prednisone in 15% and methotrexate in 23%. Importantly, 1/30 (3.3%) was positive for ANA, 4/30 (13.3%) for RF and none was positive for anti-CCP or any other autoantibodies. Complement and immunoglobulin levels were all within the normal range. Low levels of 25OHD were observed in 88% of the cases. Conclusion: Although we observed a high percentage of articular manifestations in CKV patients, the present study found a low frequency of autoantibodies in CKV patients. абстрактный Введение . Инфекция вирусом чикунгунья (CKV) может приводить к хроническому артриту у 40% пациентов. Существуют предыдущие данные о положительных аутоантителах при CKV. Цель : систематически оценивать наличие аутоантител у пациентов с CKV. Методы . У всех участников исследования были клинические проявления и положительные результаты, по крайней мере, на серологический анализ или ОТ-ПЦР на CKV. Были получены следующие аутоантитела: антинуклеарные антитела (ANA), анти-dsDNA, анти-Sm, анти-Ro / SS-A, анти-La / SS-B, анти-U1RNP, антикардиолипин IgG и IgM, антициклический цитруллинированный пептид. (анти-CCP), ревматоидный фактор (RF), анти-рибосомный P, волчаночный антикоагулянт, анти-Jo-1 и анти-Scl-70. Компоненты комплемента CH100, C3 и C4, сывороточные уровни иммуноглобулинов, C-реактивный белок, скорость оседания эритроцитов, альфа-кислотный гликопротеин, антитироглобулин, антитиропероксидаза, TRAb, 25-гидроксивитамин D (25OHD), IgG и IgM денге и вируса Зика антитела также измерялись. Результаты: было включено 30 пациентов с CKV. Средний возраст составлял 59,1 ± 15,7 лет, 85% женщин и 77% европеоидов. Давность заболевания составила 4,9 ± 4,0 мес. Олигоартрит отмечен у 93%. Средние уровни С-реактивного белка составляли 10,1 ± 6,8 нг / дл, скорость оседания эритроцитов 34,2 ± 19,9 мм / 1 час и альфа-1-кислотный гликопротеин 115,5 ± 52,6 мг / дл. Внутримышечная инъекция депо бетаметазона в разовой дозе применялась в 54% случаев, преднизон - в 15% и метотрексат - в 23%. Важно отметить, что 1/30 (3,3%) была положительной на ANA, 4/30 (13,3%) - на RF, и ни одна не была положительной на анти-CCP или любые другие аутоантитела. Уровни комплемента и иммуноглобулина были в пределах нормы. Низкие уровни 25OHD наблюдались в 88% случаев. Заключение. Хотя мы наблюдали высокий процент суставных проявлений у пациентов с CKV, настоящее исследование обнаружило низкую частоту аутоантител у пациентов с CKV.

Background Psoriasis is a multisystem inflammatory disorder with variable morphology, clinical pattern and multiple comorbidities. Interplay between genetic and environmental factors leading to an aberrant immune response in the skin may contribute to disease development. The assessment for risk factors, signs, and symptoms of potential comorbid diseases is an important component of patient management. The aim of this study is to determine rheumatoid factors (RF) positivity and its levels in psoriasis patients, and describe its relationship with the demographic and clinical characteristics, comorbidities, and disease patterns of psoriasis. Results Rheumatoid factor was positive in psoriatic patients more than control,30% of patients had positive rheumatoid factor while only 10% of control had positive results. Rheumatoid factor level was 63.8 ± 186.7 IU/ml in psoriasis vs. 9.3 ± 12.3 in control. Thirty percent of psoriasis patients have positive rheumatoid factor vs. 10% of control. There was no significant statistical difference between psoriasis patients with or without arthritis as regard rheumatoid factor positivity and titer; rheumatoid factor was positive in 20% in psoriatic patients with arthritis vs. 26% in psoriatic patients without arthritis. In psoriatic patients, the status of rheumatoid factor did not relate to disease severity, onset, course, site of affection, presence of scalp, nail affection, and presence of dactylitis (p value>0.5). Conclusion Psoriasis was associated with higher seropositivity of RF compared to age-matched non-psoriatic healthy controls. Occurrence and level of rheumatoid factor were not associated with severity or clinical pattern of psoriasis.

Background/Aims: This study was performed to clarify inf luences of anticentromere antibody (ACA) on clinical phenotypes of primary Sjögren’s syndrome (pSS) patients in Korea. Methods: We assessed 318 patients who met the 2016 American College of Rheumatology/ European League Against Rheumatism classification criteria for pSS. All patients were selected from the Korean Initiative of primary Sjögren’s Syndrome (KISS), a prospective cohort. Among them, 53 patients were positive for ACA, while another 265 patients were not. We compared various clinical data including demographic features, extra-glandular manifestations (EGMs), clinical indices, and laboratory values available from the KISS database between the two groups. Results: Patients in the ACA-positive pSS group were older (p = 0.042), and had higher xerostomia inventory scores (p = 0.040), whereas glandular dysfunction represented with Schirmer I test was more severe in the ACA-negative group. More frequent Raynaud’s phenomenon and liver involvement (both p < 0.001) and less articular involvement (p = 0.037) were observed among the EGMs in the ACA-positive group. Less frequency of leukopenia (p = 0.021), rheumatoid factor (p < 0.001), anti-Ro/SSA antibody positivity (p < 0.001), and hypergammaglobulinemia (p = 0.006), as well as higher positivity rates of anti-nuclear antibody and anti- topoisomerase antibody (p < 0.001 and p = 0.006, respectively) were found in the laboratory data in the ACA-positive pSS group. Conclusions: Considering distinct phenotypes in hematological and serological features and EGMs, we should monitor the occurrence of these clinical features among pSS patients with ACA in caution.

ObjectiveWe aimed to determine whether specific respiratory tract diseases are associated with increased rheumatoid arthritis (RA) risk.MethodsThis case-control study within the Mass General Brigham Biobank matched newly diagnosed RA cases to 3 controls on age, sex, and electronic health record history. We identified RA using a validated algorithm and confirmed by medical record review. Respiratory tract disease exposure required 1 inpatient or 2 outpatient codes at least 2 years before the index date of RA clinical diagnosis or matched date. Logistic regression models calculated ORs for RA with 95% CIs, adjusting for confounders. We then stratified by serostatus (“seropositive” was positive rheumatoid factor and/or anticitrullinated protein antibodies) and smoking.ResultsWe identified 741 RA cases and 2223 controls (both median age 55, 76% female). Acute sinusitis (OR 1.61, 95% CI 1.05–2.45), chronic sinusitis (OR 2.16, 95% CI 1.39–3.35), and asthma (OR 1.39, 95% CI 1.03–1.87) were associated with increased risk of RA. Acute respiratory tract disease burden during the preindex exposure period was also associated with increased RA risk (OR 1.30 per 10 codes, 95% CI 1.08–1.55). Acute pharyngitis was associated with seronegative (OR 1.68, 95% CI 1.02–2.74) but not seropositive RA; chronic rhinitis/pharyngitis was associated with seropositive (OR 2.46, 95% CI 1.01–5.99) but not seronegative RA. Respiratory tract diseases tended towards higher associations in smokers, especially > 10 pack-years (OR 1.52, 95% CI 1.02–2.27, P = 0.10 for interaction).ConclusionAcute and chronic sinusitis, pharyngitis, and acute respiratory burden increased RA risk. The mucosal paradigm of RA pathogenesis may involve the upper respiratory tract.

Rheumatoid arthritis (RA) is a frequent background for the development of renal pathology. Chronic kidney disease (CKD) is determined in more than 30% of patients with RA. Along with inflammation and other factors in the progression of the underlying disease, the development of renal damage in RA is facilitated by the presence of metabolic syndrome (MetS).The aim of this study is to assess the relationship of serum concentrations of angiopoietin-like proteins (ANGPTL) and antiphospholipid antibodies (aPL) with the development of renal dysfunction in patients with RA.We examined 158 patients with RA (91.8% – women and 8.2% – men) aged 21 to 80 years old and an average duration of the disease – 9 (4-15) years. The majority of patients were seropositive for rheumatoid factor and for antibodies to cyclic citrullinated peptide, with an advanced clinical stage and moderate activity (3.2 < DAS28 ≤ 5.1) of the pathological process.The ELISA test was used for the quantitative determination of angiopoietin-like protein type 3 and type 4 and antibodies to phospholipids (aРL-IgG/IgM) for total detection of antibodies to cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidylic acid and a complex of negatively charged phospholipid and β2-glycoprotein-I.More than half of the examined RA patients had the calculated glomerular filtration rate (eGFR) ranging from 89 to 60 ml/min/1.73 m2 (allocation by CKD stages: C1 – 21.5%; C2 – 58.9%; C3 – 19.6%). Signs of MetS (a combination of increased blood pressure, increased triglyceride levels and carbohydrate metabolism disorders against the background of central obesity) were diagnosed in 68 (43%) RA patients. Multivariable analysis of variance was performed to compare the studied parameters (ANGPTL3, ANGPTL4, aPL) depending on eGFR in groups of RA patients without signs of metabolic syndrome and RA patients with MetS. Significant differences in the level of ANGPTL3 (F = 8.86, p = 0.0034) and ANGPTL4 (F = 29.6, p < 0.001), but not aPL (p > 0,05) were found between RA patients with varying degrees of severity of metabolic disorders.Multivariable analysis of variance showed a significant increase in ANGPTL4 in the blood serum of RA patients with reduced eGFR (< 89 ml/min) (F = 18.5, p < 0.001) and pronounced metabolic changes (F = 24.2, p < 0.001). Thus, only two factors (renal dysfunction and the presence of MetS) had a direct effect on the ANGPTL4 content in RA patients, which could describe the variability of this sign in more than 30% of cases. The squared multiple correlation coefficient (R2 ) in this model was 0.33. ANGPTL type 4 should be considered as a key factor linking the development of renal dysfunction and metabolic changes caused by rheumatoid inflammation.

OBJECTIVE To evaluate the prevalence of elevations of anti-cyclic citrullinated peptide-3 (anti-CCP3) antibody, rheumatoid factor IgM (RF-IgM) and serum calprotectin (sCP) in pre-rheumatoid arthritis (RA) as well as the diagnostic accuracies of these biomarkers for the timing of diagnosis of future RA. METHODS A total of 215 RA cases, each with approximately three pre-RA diagnoses and one post-RA diagnosis serum sample, and controls were identified from the Department of Defense Serum Repository. All case samples and a single sample from each control subject were tested for anti-CCP3 (IgG), RF-IgM, and sCP. The diagnostic accuracies of biomarkers for future RA were evaluated. RESULTS Anti-CCP3, RF-IgM, and sCP were elevated in pre-RA, with anti-CCP3 and sCP significantly elevated compared with RF-IgM at the earliest time points. Within the cases, the combination of anti-CCP3 and RF-IgM positivity had a positive predictive value (PPV) of 35.6% for a diagnosis of RA in 3 years or less, which is significantly higher than the PPV of 18.7% for anti-CCP3 positivity alone (P < 0.001). A combination of anti-CCP3, RF-IgM, and sCP had the highest PPV (53.0%) for a diagnosis of RA in 3 years or less; however, this was not significantly higher than the PPV for anti-CCP3 and RF-IgM positivity (P = 0.248). CONCLUSION Anti-CCP3, RF-IgM, and sCP are elevated in pre-RA; furthermore, combinations of elevations of these biomarkers are more commonly seen in the period of less than or equal to 3 years to diagnosis. This may be considered in creating inclusion criteria in prevention trials in RA. In addition, the biologic relationships of these biomarkers in pre-RA need exploration.

Background: Pediatric rheumatic diseases can cause considerable disease burden to children and their families. They are associated with the potential for physical disability, diminished quality of life and significant direct and indirect costs. Objective: We aimed to describe the clinical spectrum and the frequencies and different patterns of Juvenile idiopathic arthritis (JIA) in children in Zagazig University Hospitals. Patients and methods: A cross-sectional study included 68 cases with Juvenile idiopathic arthritis < 16 years. The study was conducted over two years from December 2017 to December 2019. Investigations as complete blood count, C reactive protein, antinuclear antibody (ANA), rheumatoid factor (RF), complement C3 & C4, creatine phosphokinase, and EMG. Management and treatment plans were achieved and data about the results were collected. Results: Most of patients diagnosed with rheumatological diseases were females. Oligoarticular JIA was the commonestsubtype of JIA in our study followed by polyarticular then systemic onset type. NSAIDs was the commonest drug used by JIA patients followed by methotrexate then corticosteroids. Conclusion: Early diagnosis and effective management of these children is essential so that they can lead a normal or near normal life especially in patients with rheumatological diseases with chronic morbidity as JIA.

Background This study aims to describe the association between sharp score and clinical indexes, bone metabolism indexes, Disease Activity Score (DAS28) and sociodemographic factors in rheumatoid arthritis (RA). Methods Data were collected from the HIS (hospital information system), a national inpatient database in China, with information on the patients hospitalized during the period from 2012 to 2019. The association between sharp score and effective factors were identified using multinomial logistic regression and association rule mining (ARM). Results Three thousand eight hundred and forty patients were included: 82.66% males, 17.34% females, mean (SD) age 56.95 (12.68) years and symptom duration 3.45 (1.09) years. Spearman correlation analysis and Association rules analysis showed that there were significant positive correlations between sharp score and effective factors. Logistic regression analysis presented that erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (CRP), rheumatoid factor (RF) were risk factors of sharp score. In the analysis of individual outcomes, sex, age, symptom duration, DSA28 score, RF, ever drinker, and radiographic grading of hands were influence factors of sharp score. Conclusion Sharp score should be taken into consideration in formulating treatment strategies in RA.