Search

Inflammatory arthritis may be the principal feature or one component of an inflammatory rheumatological disease. It is a clinical diagnosis, principally made based on the patient’s history and examination. Specific investigations, such as rheumatoid factor and human leucocyte antigen B27 gene, may support the diagnosis in the context of a suggestive clinical presentation, but a diagnosis cannot be made based on these tests alone because positive results may also be seen in healthy individuals. To reduce the likelihood of false positive results, laboratory and radiological investigations should be tailored to the suspected diagnosis based on pretest probability. While musculoskeletal symptoms are a common presentation in general practice, specific features that increase suspicion of an inflammatory arthritis include prolonged morning stiffness (more than 1 hour) that is improved by exercise or movement. A broad ‘rheumatological panel’ increases the likelihood of false positive results and should be avoided to prevent unnecessary further investigations and treatment, and unwarranted anxiety in both the patient and the doctor. [ABSTRACT FROM AUTHOR]

Precise diagnostic biomarkers of anticitrullination protein antibody (ACPA)‐negative and early‐stage RA are still to be improved. We aimed to screen autoantibodies in ACPA‐negative patients and evaluated their diagnostic performance. The human genome‐wide protein arrays (HuProt arrays) were used to define specific autoantibodies from the sera of 182 RA patients and 261 disease and healthy controls. Statistical analysis was performed with SPSS 17.0. In Phase I study, 51 out of 19,275 recombinant proteins covering the whole human genome were selected. In Phase II validation study, anti‐ANAPC15 (anaphase promoting complex subunit 15) exhibited 41.8% sensitivity and 91.5% specificity among total RA patients. There were five autoantibodies increased in ACPA‐negative RA, including anti‐ANAPC15, anti‐LSP1, anti‐APBB1, anti‐parathymosin, and anti‐UBL7. Anti‐parathymosin showed the highest prevalence of 46.2% (p = 0.016) in ACPA‐negative early stage (<2 years) RA. To further improve the diagnostic efficacy, a prediction model was constructed with 44 autoantibodies. With increased threshold for RA calling, the specificity of the model is 90.8%, while the sensitivity is 66.1% (87.8% in ACPA‐positive RA and 23.8% in ACPA‐negative RA) in independent testing patients. Therefore, HuProt arrays identified RA‐associated autoantibodies that might become possible diagnostic markers, especially in early stage ACPA‐negative RA. [ABSTRACT FROM AUTHOR]

Background: Sputum immunoglobulin G (Sp-IgG) has been discovered to induce cytolytic extracellular trap cell death in eosinophils, suggesting a potential autoimmune mechanism contributing to asthma. This study aimed to explore the potential origin of Sp-IgG and identify clinically relevant subtypes of Sp-IgG that may indicate autoimmune events in asthma. Methods: This study included 165 asthmatic patients and 38 healthy volunteers. We measured Sp-IgG and its five subtypes against eosinophil inflammatory proteins (Sp-IgGEPs), including eosinophil peroxidase, eosinophil major basic protein, eosinophilderived neurotoxin, eosinophil cationic protein, and Charcot-Leyden Crystal protein in varying asthma severity. Clinical andMendelian randomization (MR) analyses were conducted. A positive Sp-IgGEPs signature (Sp-IgGEPs+) was defined when any of the five Sp-IgGEPs values exceeded the predefined cutoff thresholds, calculated as the mean values of healthy controls plus twice the standard deviation. Results: The levels of Sp-IgG and Sp-IgGEPs were significantly elevated in moderate/severe asthma than those in mild asthma/healthy groups (all p < 0.05). Sp-IgG levels were positively correlated with airway eosinophil and Sp-IgGEPs. MR analysis showed causality between eosinophil and IgG (OR = 1.02, 95%CI = 1.00-1.04, p = 0.020), and elevated IgG was a risk factor for asthma (OR = 2.05, 95%CI = 1.00-4.17, p = 0.049). Subjects with Sp-IgGEPs+ exhibited worse disease severity and served as an independent risk factor contributing to severe asthma (adjusted-OR = 5.818, adjusted-95% CI = 2.193-15.431, adjusted-p < 0.001). Receiver operating characteristic curve analysis demonstrated that the combination of Sp-IgGEPs+ with non-allergic status, an ACT score < 15, and age = 45 years, effectively predicted severe asthma (AUC = 0.84, sensitivity = 86.20%, specificity = 67.80%). Conclusion: This study identifies a significant association between airway eosinophilic inflammation, Sp-IgG, and asthma severity. The Sp-IgGEPs panel potentially serves as the specific biomarker reflecting airway autoimmune events in asthma. [ABSTRACT FROM AUTHOR]

Copyright of Die Dermatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A Consensus of Psychoimmunology Experts (Pollak et al., 2019) established a set of red flags and proposed diagnostic criteria for psychosis of autoimmune origin (AIP). Previous studies on AIP are limited by the scarcity of CSF analysis, preventing the valorization of blood anti-neuronal antibodies (Ab). The aims of this study are to determine the relative frequency and characterize AIP in a cohort of psychotic patients that underwent CSF workup. This work is a retrospective study in a tertiary psychiatric hospital. Clinical and paraclinical data were collected from medical records, and patients were classified according to Pollak et al. (2019) criteria. From 68 patients, ten (14.7%) had positive anti-neuronal antibodies (Ab): n = 5 in CSF and blood (n = 4 anti-NMDAr, n = 1 -GAD65), and n = 5 in blood only (n = 1 anti-GABAb, n = 1 -GAD65, n = 1 -SOX1, n = 1 -NMDAr, n = 1 -zic4). After 5- (2–10)-year follow-up, n = 6/68 (8.8%) had AIP diagnosis in context of autoimmune encephalitis (AE), and the remaining (n = 4/10, blood-only Ab) alternative diagnoses (n = 2 dementia, n = 1 schizophrenia, n = 1 intellectual disability). Ten of the 13 patients that fulfilled criteria for possible AIP were mimics, and only three AE had criteria for probable AIP. All AIP developed neurological manifestations (mostly cognitive dysfunction); EEG was usually abnormal (66.7%), and all had normal MRI. We found statistically significant associations between AIP/AE and systemic autoimmune disease, presentation with seizures and EEG abnormalities. All AE developed neurological symptoms alongside psychosis. Ab positivity occurred predominantly in AE but also in other neuropsychiatric disorders. Clinical suspicion based on the knowledge of the described presentations of established Ab is crucial in the psychotic patient approach. [ABSTRACT FROM AUTHOR]

Background: Ascorbic acid can regulate the function of the immune system. This study aimed to investigate the underlying mechanisms of ascorbic acid in plasma cell differentiation and rheumatoid arthritis (RA). Methods: Mice were intraperitoneally injected with either ascorbic acid or an equivalent volume of phosphate-buffered saline (PBS). To elucidate the effects of ascorbic acid on arthritis, we utilized a collagen induced arthritis mouse model (CIA). To investigate the effects of ascorbic acid on antibody response, mice were immunized with (4-Hydroxy-3-nitrophenylacetyl)-Ficoll (NP-Ficoll) or (4-hydroxy-3-nitrophenyl) acetyl-keyhole limpet hemocyanin (NP-KLH) to elicit a T-cell independent (TI) or T-cell dependent (TD) antibody response. To clarify the ability of ascorbic acid on plasma cell production, we tracked the B cell differentiation fate on the NP-specific B1-8hi BCR transgenic background. Results: Ascorbic acid-injected mice demonstrated significantly delayed disease incidence and decreased disease severity compared to PBS-injected mice. Ascorbic acid can reduce the titers of autoantibodies in both arthritis and lupus mice models. Ascorbic acid can significantly reduce the number of plasma cells and the production of antigen-specific antibodies in TI and TD antibody response. In addition, ascorbic acid can disrupt the antibody affinity maturation. Through B1-8hi adoptive transfer experiments, it has been demonstrated that ascorbic acid restrains B cell differentiation into plasma cells in a cell-intrinsic manner. After in-depth exploration, we found that ascorbic acid can block the cell cycle of B cells and promote cell apoptosis. Mechanistically, ascorbic acid inhibited the production of autoreactive plasma cells by inhibiting the Stat3 signaling pathway. Conclusion: Our study demonstrates that ascorbic acid has the ability to suppress the generation of autoreactive plasma cells, diminish the production of autoantibodies, and consequently delay the onset of rheumatoid arthritis. Highlights: Ascorbic acid intake inhibits arthritis via reducing the production of autoantibodies. Ascorbic acid restrains B cell differentiation into plasma cells. Ascorbic acid restrains STAT3 activation in B cells. [ABSTRACT FROM AUTHOR]

Objective: Ghrelin is an orexigenic peptide that becomes post-translationally modified. Natural autoantibodies to ghrelin (ghrelin-aAb) have been described in healthy subjects, in eating disorders and rheumatic diseases, with potential clinical relevance. Despite these important reports, the data base on the prevalence and physiological role is small and technical approaches for assessing ghrelin-aAb are few, encouraging respective research for improving knowledge on the potential endocrine significance. Methods: A novel immunoprecipitation assay was generated based on a fusion protein of human ghrelin with a reporter gene. Assay quality was verified with commercial antibodies. Assay characteristics and matrix effects were determined, including stability of natural ghrelin-aAb to freezing, signal linearity in dilution experiments, and comparison of different matrices. Three groups of serum samples were analyzed for ghrelin-aAb, comprising commercial sera from healthy subjects and patients with type 1 or type 2 diabetes mellitus. Results: The newly generated ghrelin-aAb assay proved sensitive, robust and reliable over a broad concentration range. Results from serum and plasma differed slightly. The signals from serum remained stable towards freezing and thawing, and in dilution experiments. Applying a mathematical criterion for outliers (P75 + 1.5-times IQR), an average prevalence of 11%–12% of positive samples was identified in the different human cohorts, with no significant sexor disease-related difference. General significance: A novel diagnostic autoantibody assay detected ghrelinaAb with a similar prevalence in diabetic patients and controls, suggesting that autoimmunity to ghrelin plays little role in diabetes mellitus, but may be of relevance in other diseases where ghrelin signaling is essential. [ABSTRACT FROM AUTHOR]

Autoantibodies against proteins in the brain are increasingly considered as a potential cause of cognitive decline, not only in subacute autoimmune encephalopathies but also in slowly progressing impairment of memory in patients with classical neurodegenerative dementias. In this retrospective cohort study of 161 well-characterized patients with different forms of dementia and 34 controls, we determined the prevalence of immunoglobulin (Ig) G and IgA autoantibodies to brain proteins using unbiased immunofluorescence staining of unfixed murine brain sections. Autoantibodies were detected in 21.1% of dementia patients and in 2.9% of gender-matched controls, with higher frequencies in vascular dementia (42%), Alzheimer's disease (30%), dementia of unknown cause (25%), and subjective cognitive impairment (16.7%). Underlying antigens involved glial fibrillary acidic protein (GFAP), glycine receptor, and Rho GTPase activating protein 26 (ARHGAP26), but also a range of yet undetermined epitopes on neurons, myelinated fiber tracts, choroid plexus, glial cells, and blood vessels. Antibody-positive patients were younger than antibody-negative patients but did not differ in the extent of cognitive impairment, epidemiological and clinical factors, or comorbidities. Further research is needed to understand the potential contribution to disease progression and symptomatology, and to determine the antigenic targets of dementia-associated autoantibodies. [ABSTRACT FROM AUTHOR]

This study investigates the presence of antinuclear antibodies (ANA) in three primary synucleinopathies – Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), compared to healthy controls. Autoinflammatory disorders typically involve the immune system mistakenly attacking the body's own cells and start producing ANA. There is an increasing body of evidence that immune-mediated inflammation is a pathological feature linked to synucleinopathies. To investigate whether this could be autoimmune mediated we analyzed for ANA in the plasma of 25 MSA, 25 PD, and 17 DLB patients, along with 25 healthy controls, using the ANA HEp-2 indirect immunofluorescence antibody assay (ANA HEp-2 IFA). Contrary to initial expectations, results showed ANA HEp-2 positivity in 12% of PD, 8% of MSA patients, 18% of DLB patients, and 17% of healthy controls, indicating no increased prevalence of ANA in synucleinopathies compared to age-matched healthy individuals. Various ANA HEp-2 patterns were identified, but no specific pattern was associated with individual synucleinopathies. We conclude hereby that synucleinopathies are not associated with detectable presence of ANA in plasma. [ABSTRACT FROM AUTHOR]

Myositis with anti-Ku-autoantibodies is a rare inflammatory myopathy associated with various connective tissue diseases. Histopathological studies have identified inflammatory and necrotizing aspects, but a precise morphological analysis and pathomechanistic disease model are lacking. We therefore aimed to carry out an in-depth morpho-molecular analysis to uncover possible pathomechanisms. Muscle biopsy specimens from 26 patients with anti-Ku-antibodies and unequivocal myositis were analyzed by immunohistochemistry, immunofluorescence, transcriptomics, and proteomics and compared to biopsy specimens of non-disease controls, immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Clinical findings and laboratory parameters were evaluated retrospectively and correlated with morphological and molecular features. Patients were mainly female (92%) with a median age of 56.5 years. Isolated myositis and overlap with systemic sclerosis were reported in 31%, respectively. Isolated myositis presented with higher creatine kinase levels and cardiac involvement (83%), whereas systemic sclerosis-overlap patients often had interstitial lung disease (57%). Histopathology showed a wide spectrum from mild to pronounced myositis with diffuse sarcolemmal MHC-class I (100%) and -II (69%) immunoreactivity, myofiber necrosis (88%), endomysial inflammation (85%), thickened capillaries (84%), and vacuoles (60%). Conspicuous sarcoplasmic protein aggregates were p62, BAG3, myotilin, or immunoproteasomal beta5i-positive. Proteomic and transcriptomic analysis identified prominent up-regulation of autophagy, proteasome, and hnRNP-related cell stress. To conclude, Ku + myositis is morphologically characterized by myofiber necrosis, MHC-class I and II positivity, variable endomysial inflammation, and distinct protein aggregation varying from IBM and IMNM, and it can be placed in the spectrum of scleromyositis and overlap myositis. It features characteristic sarcoplasmic protein aggregation on an acquired basis being functionally associated with altered chaperone, proteasome, and autophagy function indicating that Ku + myositis exhibit aspects of an acquired inflammatory protein-aggregate myopathy. [ABSTRACT FROM AUTHOR]

The Ro60/SSA2 autoantigen is an RNA-binding protein and a core component of nucleocytoplasmic ribonucleoprotein (RNP) complexes. Ro60 is essential in RNA metabolism, cell stress response pathways, and cellular homeostasis. It stabilises and mediates the quality control and cellular distribution of small RNAs, including YRNAs (for the 'y' in 'cytoplasmic'), retroelement transcripts, and misfolded RNAs. Ro60 transcriptional dysregulation or loss of function can result in the generation and release of RNA fragments from YRNAs and other small RNAs. Small RNA fragments can instigate an inflammatory cascade through endosomal toll-like receptors (TLRs) and cytoplasmic RNA sensors, which typically sense pathogen-associated molecular patterns, and mount the first line of defence against invading pathogens. However, the recognition of host-originating RNA moieties from Ro60 RNP complexes can activate inflammatory response pathways and compromise self-tolerance. Autoreactive B cells may produce antibodies targeting extracellular Ro60 RNP complexes. Ro60 autoantibodies serve as diagnostic markers for various autoimmune diseases, including Sjögren's disease (SjD) and systemic lupus erythematosus (SLE), and they may also act as predictive markers for anti-drug antibody responses among rheumatic patients. Understanding Ro60's structure, function, and role in self-tolerance can enhance our understanding of the underlying molecular mechanisms of autoimmune conditions. [ABSTRACT FROM AUTHOR]

The 3 Screen ICA ELISA is a novel assay capable of simultaneously measuring autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A), making it a valuable tool for screening type 1 diabetes. Despite its advantages, it cannot specify which individual autoantibodies are positive or negative. This study aimed to estimate individual positive autoantibodies based on the 3 Screen ICA titer. Six hundred seventeen patients with type 1 diabetes, simultaneously measured for 3 Screen ICA and three individual autoantibodies, were divided into five groups based on their 3 Screen ICA titer. The sensitivities and contribution rates of the individual autoantibodies were then examined. The study had a cross-sectional design. Sixty-nine percent (424 of 617) of patients with type 1 diabetes had 3 Screen ICA titers exceeding the 99th percentile cut-off level (20 index). The prevalence of GADA ranged from 80% to 100% in patients with a 3 Screen ICA over 30 index and 97% of patients with a 3 Screen ICA ≥300 index. Furthermore, the prevalence of all individual autoantibodies being positive was 0% for ≤80 index and as high as 92% for ≥300 index. Significant associations were observed in specific titer groups: the 20–29.9 index group when all the individual autoantibodies were negative, the 30–79.9 index group when positive for GADA alone or IA-2A alone, the 30–299.9 index group when positive for ZnT8A alone, the 80–299.9 index group when positive for both IA-2A and ZnT8A, the 300–499.9 index group when positive for both GADA and ZnT8A, and the ≥300 index group when positive for all individual autoantibodies. These results suggest that the 3 Screen ICA titer may be helpful in estimating individual positive autoantibodies. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSAs/MAAs) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n = 558). Our PH cohort (n = 121) showed a significantly higher prevalence of overall weak positive MSAs/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p < 0.001). Notably, MSAs/MAAs were found in PH patients both with and without ILD, though more prevalent in those with ILD. Anti-synthetase and anti-overlap syndrome antibodies were the most common. Our study is the first to systematically show a high MSA/MAA prevalence in PH without IIM presentation. This highlights the need to consider PH when diagnosing MSA/MAA-associated conditions. We recommend MSA/MAA screening for newly diagnosed PH, especially in those with ILD, for early detection and potential immunomodulatory treatment. Further research should explore the link between MSAs/MAAs and PH, and the value of monitoring patients with weak MSA/MAA positivity over time. [ABSTRACT FROM AUTHOR]

Objective: The long-lasting persistence of autoantibodies stands as one of the hypotheses explaining the multisystemic manifestations seen in individuals with post-COVID-19 condition. The current review offers restricted insights into the persistence of autoantibodies in plasma/serum in people with post-COVID symptoms. Methods: PubMed/MEDLINE, CINAHL, EMBASE, and Web of Science databases, as well as on medRxiv and bioRxiv preprint servers were searched up to January 5th, 2024. Papers investigating the presence of autoantibodies in plasma/serum samples in people with post-COVID symptoms were included. The Newcastle-Ottawa Scale (NOS) was used to assess methodological quality. Results: From 162 identified records, five articles met all inclusion criteria; four studies included infected controls with no post-COVID symptoms whereas all five studies included non-infected controls (410 COVID-19 survivors with post-COVID symptoms, 223 COVID-19 survivors with no post-COVID symptoms as controls and 266 non-infected healthy controls). Four studies concluded that the presence of autoantibodies had a potential (but small) role in post-COVID-19 condition whereas one study concluded that autoantibodies were not associated. Quality assessment showed all studies had high methodological quality. Conclusion: Although evidence suggests that persistent autoantibodies can be associated with post-COVID symptoms, the clinical relevance of their presence seems modest at this stage. Current results highlight further research to clarify the role of autoantibodies in the development of post-COVID symptoms, guiding the development of tailored diagnostic and treatment approaches to enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Regardless of microbial virulence (i.e., the global infection-fatality ratio), age generally drives the prevalence of death from infection in unvaccinated humans. Four mortality patterns are recognized: the common U- and L-shaped curves of endemic infections and the unique W- and J-shaped curves of pandemic infections. We suggest that these patterns result from different sets of human genetic and immunological determinants. In this model, it is the interplay between (1) monogenic genotypes affecting immunity to primary infection that preferentially manifest early in life and related genotypes or their phenocopies, including auto-antibodies, which manifest later in life and (2) the occurrence and persistence of adaptive, acquired immunity to primary or cross-reactive infections, which shapes the age-dependent pattern of human deaths from infection. We suggest that the U, L, W, and J age-dependent patterns of death from infection result from the interplay between (1) genotypes affecting immunity to primary infection, related genotypes, or their phenocopies later in life and (2) the occurrence and persistence of adaptive, acquired immunity to primary or cross-reactive infections. [ABSTRACT FROM AUTHOR]

The given text is a list of references to various scientific articles related to immunology and autoimmune diseases. The articles cover topics such as the influence of HLA class II molecules on inflammatory diseases, the role of DNases in health and disease, polymorphisms associated with rheumatoid arthritis, and the overlap in neutrophil transcriptome between lupus and COVID-19. Other articles discuss the role of alternative splicing in cancer and autoimmune diseases, the expression of retroviruses in rheumatoid arthritis and lupus, and the presence of autoantibodies in autoimmune diseases. These articles provide valuable insights into the mechanisms and potential therapeutic targets for these diseases. [Extracted from the article]

Objective: It is well known that macro-thyroid-stimulating hormone (macro-TSH) could interfere with the detection of TSH. The anti-TSH autoantibody is an essential component of macro-TSH. However, the epidemiological characteristics and the clinical interference of the anti-TSH autoantibody are unclear. Methods: In this study, the radioimmunoprecipitation technique was used to detect the anti-TSH autoantibody. Platforms with different detection mechanisms were applied to measure the TSH in patients with the anti-TSH autoantibody. Polyethylene glycol (PEG) precipitation was used to determine the immunoassay interference. Results: The prevalence of the anti-TSH autoantibody in patients with mild subclinical hypothyroidism (SCH) and autoimmune thyroiditis, but normal thyroid function, was 4.78%. All 10 patients with anti-TSH antibodies had autoimmune diseases, with five of them having significant clinical test interference. Conclusion: The appearance of the anti-TSH antibody is not associated with thyroid autoantibodies. The presence of the anti-TSH autoantibody can interfere with the detection of TSH and can affect clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Anti-citrullinated protein autoantibodies (ACPA) are diagnostic for rheumatoid arthritis (RA). The antigens recognized by these autoantibodies are produced by protein arginine deiminases (PADs), particularly PAD4. However, it remains unknown why and how PAD4 causes this aberrant citrullination in RA. Here, we report that poly-perforin pores are present on freshly isolated neutrophils from RA patients, but not on healthy donor neutrophils. Neutrophils with perforin pores also contained intracellular citrullinated proteins in the region adjacent to the pores. This response was replicated in vitro by treating neutrophils with purified perforin, which generated intense dots of anti-perforin immunofluorescence, calcium influx, and intracellular citrullination. Extensive neutrophil killing in Felty's syndrome, an aggressive form of RA, correlated with particularly high ACPA, and PAD4 autoantibodies. In contrast, other forms of death, including NETosis, apoptosis, and pyroptosis, produced minimal citrullination. We conclude that neutrophil targeting by perforin leading to intracellular citrullination takes place in patients with RA. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Both conditions are characterized by systemic inflammation that contributes to an increased risk of CVD, yet the underlying mechanisms and associated risk factors differ. This review investigates the immunological responses, inflammatory pathways, and genetic predispositions that influence the risk of cardiovascular disease (CV) in people with RA and PsA. Endothelial dysfunction and atherosclerosis in RA are primarily caused by pro-inflammatory cytokines, specifically interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-a), as well as the existence of autoantibodies such as anti-citrullinated protein antibodies (ACPA). Additionally, RA displays a "lipid paradox," in which a decreased risk of CVD is paradoxically correlated with a higher risk of cholesterol, most likely as a result of ongoing systemic inflammation. Different paths of CV impact are indicated by unique lipid profile changes and less prominent autoantibody participation in PsA, despite the fact that the risk of CVD is also enhanced. Genetic factors like HLA-DRB1 are more prominent in RA, while PsA has a unique association with metabolic syndrome and obesity-related inflammation. Despite the well-established CV risk in both RA and PsA, current risk calculators do not include PsA, and only two models account for RA. This review highlights the need for better risk assessment tools that incorporate disease-specific factors. Recognizing the overlapping and divergent mechanisms in RA and PsA can enhance the development of more targeted strategies for managing CV health and guide personalized treatment approaches. [ABSTRACT FROM AUTHOR]

Background: Celiac disease, a prevalent autoimmune disorder, frequently coexists with various syndromes and autoimmune conditions. The leading cause of acquired hypothyroidism, wherein T cells target the thyroperoxidase enzyme, causing irreversible damage to the thyroid gland. According to the conflicting results presented in the studies, we aimed to determine the relationship between celiac disease and thyroid ultrasound findings. Materials and Methods: 62 patients who were referred to the hospital and suffering from celiac disease were included in the study. After obtaining informed consent from the patients, a questionnaire related to demographic characteristics, including age and sex, was completed, and the patients were subjected to ultrasonography of the thyroid gland. The collected information was entered into SPSS software version 16 for data analysis. Results: The mean duration of celiac disease was 6.03 years. No cases of heterogeneity were found in the thyroid ultrasonography of the healthy control group, but in the group of celiac patients, 24 cases (38.7%) had heterogeneous thyroids. In the ultrasound examination, the average volume of the left and right lobes and the thickness of the thyroid isthmus in the group of celiac patients was significantly smaller than that of healthy individuals. (P<0.05). In the sonographic examination of the thyroid of patients with celiac disease, six patients who had a heterogeneous appearance also had Hashimoto's. The prevalence of thyroid nodularity was 35.5% in celiac patients and 5.7% in the control group (P<0.001). Conclusion: Thyroid ultrasonography in patients with celiac disease shows gland shrinkage, diffuse heterogeneity, nodularity, and typical manifestations of Hashimoto's thyroiditis compared with the normal population. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is a type of autoimmune disease (AID) of the skin that is acquired and characterized by loss of melanocytes. The precise cause of vitiligo is still not well-identified. Autoimmune theory is the most supported by reliable laboratory and clinical data, particularly for non-segmental vitiligo (NSV). Objective: This study aimed to compare the levels of circulating autoantibodies namely anti-thyroperoxidase Ab (anti-TPO), anti-melanocyte Ab (AMA), anti-nuclear Ab (ANA), in the sera of vitiligo patients versus controls. Patients and Methods: This was a case-control study enrolled 50 vitiligo cases and40 healthy with matched age and sex as control group. The degree of vitiligo was assessed using the vitiligo area severity index (VASI) score. All patients and controls had laboratory test for measurement of anti-thyroperoxidase Ab, anti-melanocyte Ab and anti-nuclear Ab by ELISA kits. Results: There were significantly higher median levels of anti-TPO Ab, AMA and ANA compared to the control group. There were no significant differences in anti-TPO Ab levels, AMA levels and ANA levels based on gender, smoking status, and family history. There was a significant positive relationship between levels of anti-TPO Ab, AMA and ANA and the VASI score. Conclusion: There was a potential relationship between anti-TPO Ab levels, AMA levels & ANA levels and disease severity. These results suggest that higher levels of these antibodies are associated with increased disease severity (assessed by VASI) in vitiligo patients. Keywords: Vitiligo, Autoimmune, Anti-thyroid peroxidase, Anti-melanocyte Ab, Anti-nuclear Ab, Vitiligo area severity index [ABSTRACT FROM AUTHOR]

Objectives: This cross-sectional study was designed to assess the clinical profile and frequency of associated autoantibodies in all consecutive patients classified as systemic sclerosis (SSc) at Medanta—the Medicity Hospital, Gurgaon, India. Methods: Between August 2017 and July 2019, we identified a total of 119 consecutive patients meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2013 criteria for SSc and 106 patients consented to this study. Their clinical and serological data at the time of enrolment were analysed. Results: Our cohort had a mean age at symptom onset of 40 ± 13 years with a median symptom duration of 6 years. We had 76 patients (71.7%) with interstitial lung disease (ILD), which was a higher proportion compared to European cohorts. 62 pa- tients (58.5%) had diffuse cutaneous involvement which was significantly associated with anti-Scl70 antibodies (p < 0.001), digital ulcers (p = 0.039) and the presence of ILD (p = 0.004). 65 patients (61.3%) had anti-Scl70 and 15 patients (14.2%) had anti-centromere (anti-CENP) antibodies. Scl70 positivity was associated with the presence of ILD (p < 0.001) and digital ulcers (p = 0.01). Centromere antibodies had a negative association with ILD (p < 0.001), but was a risk factor for calcinosis (p < 0.001) and pulmonary arterial hypertension (PAH) (p = 0.01). The combination of diffuse cutaneous disease and Scl70 antibodies was the strongest predictor of ILD and digital ulcers (p = 0.015). sm/RMP, RNP68 and Ku antibodies correlated with musculoskeletal involvement (p < 0.01), while all seven of the patients with Pm/Scl antibodies had ILD. Renal involve- ment was noted in only two patients. Limitations: A single-centre study may not capture the true prevalence of disease characteristics in the population. Referral bias for patients with diffuse cutaneous disease has been noted. Data on RNA-Polymerase antibodies have not been provided. Conclusion: North Indian patients have some characteristic differences in disease phenotype as compared to their Caucasian counterparts with a larger proportion of patients presenting with ILD and Scl70 antibodies. Antibodies against Ku, RNP and Pm/Scl occur in a minority of patients, but may be associated with musculoskeletal features. [ABSTRACT FROM AUTHOR]

A 23-year-old man presented with multiple asymptomatic blisters over the trunk and extremities for the past 2 years. The blisters would rupture in 1-2 days and heal with hyperpigmentation. The patient was diagnosed with pemphigus herpetiformis based on clinical and immunopathological findings. Treatment with oral dapsone resulted in complete resolution of the lesions within 8 weeks. Pemphigus herpetiformis is a rare variant of pemphigus and can be misdiagnosed as other conditions such as tinea corporis. It is important to accurately diagnose this condition due to its better prognosis and response to treatment. [Extracted from the article]

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of large amounts of autoantibodies and immune complex formation. Because of their atypical clinical symptoms, SLE patients with digestive system involvement may not be recognized or treated precisely and extensively. Clinicians should pay close attention to SLE with digestive system involvement, as these conditions can easily worsen the condition and possibly endanger the patient's life. In this review we summarized the pathogenesis, pathological characteristics, clinical manifestations, diagnosis, and therapies for digestive system involvement in SLE. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP) is the most common autoimmune blistering disease and results from autoantibodies against hemidesmosomal proteins of the basement membrane. Occurrence of BP in patients with human immunodeficiency virus (HIV) has already been described. We report an exuberant case of BP in a HIV carrier aiming to emphasize the difficulty of treating this entity in this population. [ABSTRACT FROM AUTHOR]

Pemphigus erythematosus (PE) is a rare disorder that belongs to a group of chronic autoimmune blistering diseases. It is a form of pemphigus with an overlapping clinical and immunological presentation of pemphigus foliaceus and lupus erythematosus, mediated by autoantibodies targeting desmoglein 1. It has a broad clinical spectrum, and severe cases can result in multi-organ compromise. To date, there is no established treatment for severe cases of PE. We describe a case of a previously healthy patient with a 4-month clinical course of generalized painful erythematous desquamative plaques and blisters, associated with a 10 kg weight loss. The clinical and histopathological findings were consistent with PE. An adjusted rituximab protocol was used, achieving disease remission within 20 days. Rituximab is the mainstay of therapy and a well-known effective treatment for pemphigus vulgaris with a prolonged remission; nevertheless, there are no established protocols and limited evidence in PE. [ABSTRACT FROM AUTHOR]

Stiff-person syndrome (SPS) is a rare and complex neurologic disorder characterized by progressive muscle stiffness, painful spasms, and gait difficulties. In this report, we describe a case of SPS who presented with a relapse while on maintenance immunosuppressive treatment. In addition, we review the literature of 16 previously reported cases of SPS from India, highlighting the diverse clinical features, comorbidities, treatment response, and relapse. The occurrence of paraneoplastic SPS emphasizes the need for early recognition and diagnosis. [ABSTRACT FROM AUTHOR]

Background: Pemphigus is a group of potentially life-threatening autoimmune bullous diseases induced by pathogenic autoantibodies binding to the surface of epidermal cells. The role of the gut microbiota (GM) has been described in various autoimmune diseases. However, the impact of the GM on pemphigus is less understood. This study aimed to investigate whether there was alterations in the composition and function of the GM in pemphigus patients compared to healthy controls (HCs). Methods: Fecal samples were collected from 20 patients with active pemphigus (AP), 11 patients with remission pemphigus (PR), and 47 HCs. To sequence the fecal samples, 16S rRNA was applied, and bioinformatic analyses were performed. Results: We found differences in the abundance of certain bacterial taxa among the three groups. At the family level, the abundance of Prevotellaceae and Coriobacteriaceae positively correlated with pathogenic autoantibodies. At the genus level, the abundance of Klebsiella, Akkermansia, Bifidobacterium, Collinsella, Gemmiger, and Prevotella positively correlated with pathogenic autoantibodies. Meanwhile, the abundance of Veillonella and Clostridium_XlVa negatively correlated with pathogenic autoantibodies. A BugBase analysis revealed that the sum of potentially pathogenic bacteria was elevated in the AP group in comparison to the PR group. Additionally, the proportion of Gram-negative bacteria in the PR group was statistically significantly lower in comparison to the HC group. Conclusion: The differences in GM composition among the three groups, and the correlation between certain bacterial taxa and pathogenic autoantibodies of pemphigus, support a linkage between the GM and pemphigus. [ABSTRACT FROM AUTHOR]

Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between islet autoantibodies (IAbs) and the retinal neurovascular changes in type 1 diabetes mellitus (T1DM) with no diabetic retinopathy (NDR). Methods: This cross-sectional study measured the neural retinal structure and microvascular density of 118 NDR eyes using spectral-domain optical coherence tomography angiography. Retinal structure parameters included retinal thickness (RT), inner retinal thickness (iRT), retina never fibral layer thickness (RNFL thickness), ganglion cell complex thickness (GCC thickness), and loss volume of GCC. Microvascular parameters included vessel density of superficial capillary plexus (sVD), vessel density of deep capillary plexus, and vessel density of choroid capillary plexus. Comparison and correlation analyses of these OCTA parameters were made with various IAbs, including glutamic acid decarboxylase antibody (GADA), tyrosine phosphatase-related islet antigen 2 antibody (IA2A), and zinc transporter 8 antibody (ZnT8A). A general linear model was used to understand the association of IAbs with the retina parameters. Results: The IAb positive (IAbs +) group, which included 85 patients, had thinner RT (235.20 ± 18.10 mm vs. 244.40 ± 19.90 mm at fovea, P = 0.021) and thinner iRT (120.10 ± 9.00 mm vs. 124.70 ± 6.90 mm at parafovea, P = 0.015), compared with the IAb negative (IAbs-) group comprising 33 patients. Furthermore, a more severe reduction of RT was demonstrated in the presence of multiple IAbs. Among the three IAbs, GADA was the most significant independent risk factor of all-round RT decrease (β = −0.20 vs. −0.27 at fovea and parafovea, respectively, P < 0.05), while titers of IA2A negatively affect sVD in the parafovea (β = −0.316, P = 0.003). Conclusions: IAbs are associated with neural retinal thinning and microcirculation reduction in T1DM patients before the clinical onset of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Aims/Introduction: This study aimed to identify risk factors that contribute to the progression of slowly‐progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin‐dependent state. Materials and Methods: We selected 60 slowly‐progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme‐linked immunosorbent assay (ELISA) techniques. Results: Compared with the non‐progressor group (fasting C‐peptide [F‐CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F‐CPR levels and a higher prevalence of insulinoma‐associated antigen‐2 autoantibodies (IA‐2A). The PPV of RIA‐GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis <47 years, BMI <22.6 kg/m2, F‐CPR <1.41 ng/mL and IA‐2A positivity, respectively. In contrast, the PPV of ELISA‐GADA (71.8%) remained the same at 73.1% in the high titer group (≥180 U/mL), but increased to 81.8, 82.4 and 79.0% when evaluated in conjunction with age at diagnosis, BMI and F‐CPR level, respectively. Conclusions: Our findings show that, unlike RIA‐GADA, ELISA‐GADA shows no association between GADA titers and the risk of progression to an insulin‐dependent state. The PPV improves when age at diagnosis, BMI and F‐CPR levels are considered in combination. [ABSTRACT FROM AUTHOR]

Since entering the stage 25 years ago as a highly specific serological biomarker for rheumatoid arthritis, anti-citrullinated protein antibodies (ACPAs) have been a topic of extensive research. This hallmark B cell response arises years before disease onset, displays interpatient autoantigen variability, and is associated with poor clinical outcomes. Technological and scientific advances have revealed broad clonal diversity and intriguing features including high levels of somatic hypermutation, variable-domain N-linked glycosylation, hapten-like peptide interactions, and clone-specific multireactivity to citrullinated, carbamylated and acetylated epitopes. ACPAs have been found in different isotypes and subclasses, in both circulation and tissue, and are secreted by both plasmablasts and long-lived plasma cells. Notably, although some disease-promoting features have been reported, results now demonstrate that certain monoclonal ACPAs therapeutically block arthritis and inflammation in mouse models. A wealth of functional studies using patient-derived polyclonal and monoclonal antibodies have provided evidence for pathogenic and protective effects of ACPAs in the context of arthritis. To understand the roles of ACPAs, one needs to consider their immunological properties by incorporating different facets such as rheumatoid arthritis B cell biology, environmental triggers and chronic antigen exposure. The emerging picture points to a complex role of citrulline-reactive autoantibodies, in which the diversity and dynamics of antibody clones could determine clinical progression and manifestations. In this Review, the authors provide an overview of the immunological, clinical and pathophysiological features of anti-citrullinated protein antibodies in rheumatoid arthritis, highlighting the latest findings regarding the complex contribution of anti-citrullinated protein antibodies to the disease. Key points: Citrulline B cell responses are diverse but share important features that might be linked to rheumatoid arthritis-associated B cell dysregulation as well as environmental triggers, antigen exposure and the evolution of chronic immune reactions. Anti-citrullinated protein antibodies (ACPAs) are extensively multireactive towards citrullinated, carbamylated and acetylated proteins, have high somatic hypermutation, and carry N-linked glycosylations in the variable regions. More than 100 patient-derived human monoclonal ACPAs have been generated from different B cell compartments and patients, providing invaluable insights into citrulline autoimmunity and antibody function. Although disease-causative autoantigens are presently unknown, ACPAs can target different synovial cells and are likely to form pathogenic immune complexes. Results from studies using human monoclonal ACPAs reveal that some clones can completely block arthritis and inflammation in mouse models, while showing moderate pathogenic properties in other settings. Different ACPA clones with different immunological features and antigen-binding patterns might mediate disease-promoting effects or have protective roles. [ABSTRACT FROM AUTHOR]

Background: Plasma exchanges (PEX) and immunosuppression are the cornerstone of management of anti-factor H (FH) antibody-associated atypical hemolytic uremic syndrome (aHUS), particularly if access to eculizumab is limited. The duration of therapy with PEX for anti-FH aHUS is empirical. Methods: We compared the efficacy of abbreviated PEX protocol (10–12 sessions) in a prospective cohort of patients diagnosed with anti-FH aHUS (2020–2022), to standard PEX protocol (20–22 sessions) in a historical cohort (2016–2019; n = 65). Efficacy was defined as 70% decline in anti-FH titers or fall to ≤ 1300 AU/ml at 4 weeks. Patients in both cohorts received similar immunosuppression with oral prednisolone, IV cyclophosphamide (5 doses) and mycophenolate mofetil. Outcomes included efficacy, rates of hematological remission and adverse kidney outcomes at 1, 3 and 6 months. Results: Of 23 patients, 8.2 ± 2.1 years old enrolled prospectively, two were excluded for significant protocol deviation. PEX was abbreviated in 18/21 (86%) patients to 11.5 ± 3.3 sessions. Abbreviation failed for lack of hematological remission by day 14 (n = 2) and persistent neurological manifestations (n = 1). All patients in whom PEX was abbreviated achieved > 70% reduction in anti-FH titers at day 28. The percentage fall in anti-FH titers was similar for the abbreviated vs. standard PEX protocols at 1, 3 and 6 months. At last follow-up, at median 50 months and 25 months for standard and abbreviated cohorts, the estimated GFR was similar at 104.8 ± 29.1 vs. 93.7 ± 53.4, respectively (P = 0.42). Conclusion: Abbreviation of the duration of PEX is feasible and efficacious in reducing anti-FH titers. Short-term outcomes were comparable in patients managed by abbreviated and standard PEX protocols. [ABSTRACT FROM AUTHOR]

Objectives Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (MDA5+) dermatomyositis patients exhibit a variety of clinical features. We therefore investigated whether patterns of B-cell epitope recognition are linked to the clinical course of MDA5+ dermatomyositis. Methods Our cross-sectional study used ELISA-based methods to determine the relationship between antibody recognition of overlapping 155 amino acid MDA5 subfragments and clinical features of 24 MDA5+ myositis patients. Correlations between clinical features and standardized anti-MDA5 subfragment antibody titres were assessed via Spearman's rank correlation coefficients. Results Twenty-four MDA5+ patients submitted serum samples within a median of 0 (interquartile range, 0–74) days from the initial clinic visit. In addition to typical dermatomyositis rashes, these patients exhibited muscle symptoms (n  = 11), vascular dysfunction (n  = 9) and interstitial lung disease (ILD) (n  = 16). Female patients exhibited higher titres of antibodies recognizing fragment H (aa 905–1026) compared with male patients. Muscle involvement was associated with higher levels of anti-fragment F (aa 646–801) antibody. Conversely, patients with vascular abnormalities had higher anti-fragment B (aa 130–284) and E (aa 517–671) antibody titres than those without vascular dysfunction. Four patients died due to ILD progression and showed higher anti-fragment A (aa 1–155) antibody titres than the other 20 patients. Differences in the ratio of anti-fragment to anti-full-length MDA5 antibody titres were found for sex (H: anti-MDA5) and vascular dysfunction (anti-fragment B, E: anti-MDA5). Conclusions Various clinical features of MDA5+ dermatomyositis correlated with levels of antibodies targeting selected subfragments of this autoantigen, providing a link between fragment-specific immune responses and disease course. [ABSTRACT FROM AUTHOR]

Objectives Taxifolin (dihydroquercetin) is a bioactive plant flavonoid that exhibits anti-inflammatory and anti-oxidative properties. We hypothesized that taxifolin might be an effective dietary supplement to ameliorate symptoms arising from thrombo-inflammatory diseases such as lupus and APS. Methods We used in vitro assays and a mouse model to determine mechanisms by which taxifolin inhibits neutrophil extracellular trap (NET) formation (i.e. NETosis) and venous thrombosis in lupus and APS. Results At doses ranging from 0.1 to 1 µg/ml, taxifolin inhibited NETosis from control neutrophils stimulated with autoantibodies isolated from lupus and APS patients, and its suppressive effects were mitigated by blocking the antioxidant transcription factor Nrf2 (nuclear factor erythroid 2–related factor 2). Furthermore, taxifolin at a dose as low as 20 mg/kg/day reduced in vivo NETosis in thrombo-inflammatory mouse models of lupus and APS while also significantly attenuating autoantibody formation, inflammatory cytokine production and large-vein thrombosis. Conclusion Our study is the first to demonstrate the protective effects of taxifolin in the context of lupus and APS. Importantly, our study also suggests a therapeutic potential to neutralize neutrophil hyperactivity and NETosis that could have relevance to a variety of thrombo-inflammatory diseases. [ABSTRACT FROM AUTHOR]

Objectives Paraneoplastic arthritis (PA) is one of the paraneoplastic syndromes. Both laboratory and clinical findings similar to rheumatological diseases can be seen. In this study we aimed to present the clinical and laboratory findings, malignancy types and pathological diagnoses of patients with paraneoplastic arthritis. Methods In a multicentre retrospective study, 92 patients with PA from the last 10 years were included. Results Patients with PA and haematological malignancies exhibited the highest ratio of lymphomas (25.6%). The most common cancer detected in patients with solid malignancy and PA was lung cancer (41.5%). All malignant patients with PA had significant anti-CCP positivity compared with the healthy control group (P  = 0.014). Conclusion Although PA is a rare condition, it can be confused with many rheumatological diseases. The most commonly involved joint is the knee joint, followed by the ankle and hand/wrist. Autoantibody negativity, high lactate dehydrogenase level and arthritis unresponsive to treatment constitute important clues for diagnosis. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether the efficacy and safety data from drug-registration trials can be extrapolated to real-life RA patients receiving RTX. Methods The 'AutoImmunity and Rituximab' (AIR-PR) registry is a French multicentre, prospective cohort of RA patients treated with RTX in a real-life setting. We compared treatment responses at 12 months and serious adverse events (AEs) between eligible and non-eligible patients, by retrieving the eligibility criteria of the three rituximab-registration trials. We determined critical eligibility criteria and modelled the benefit–risk ratio according to the number of fulfilled critical eligibility criteria. Results Among 1984 RA patients, only 9–12% fulfilled all eligibility criteria. Non-eligible patients had fewer EULAR responses at 12 months (40.3% vs 46.9%, P  = 0.044). Critical inclusion criteria included swollen joints count ≥4, tender joints count ≥4, CRP ≥15 mg/l and RF positivity. Critical exclusion criteria were age >80 years, RA-associated systemic diseases, ACR functional class IV, DMARD other than MTX and prednisone >10 mg/day. Only 20.8% fulfilled those critical eligibility criteria. During the first year, serious AEs occurred for 182 (9.2%) patients (70.3% serious infections) and patients with ≥1 critical exclusion criterion were at higher risk (hazard ratio 3.03; 95% CI 2.25–4.06; for ≥3 criteria vs 0). The incremental risk–benefit ratio decreased with the number of unmet critical inclusion criteria and of fulfilled exclusion criteria. Conclusion Few real-life RA patients were eligible for the drug-registration trials. Non-eligible patients had lower chance of response, and higher risk of serious AEs. Efficacy and safety data obtained from those trials may not be generalizable to RA patients receiving RTX in real-world clinical practice. [ABSTRACT FROM AUTHOR]

Summary: A retrospective analysis was conducted using data from the NHANES. Bone mineral density (BMD) was compared in different thyroid-specific autoantibodies groups. Strengths of associations were calculated by using binary logistic regression models. Higher titers of thyroid-specific autoantibodies (TgAb and/or TPOAb) may lead to decreased BMD. Higher prevalence of TgAb and TPOAb significantly associated with fractures in females but not in males. Purpose: Hashimoto's thyroiditis is characterized by elevated thyroid-specific autoantibodies. It is currently believed that osteoporosis is not only a disease with abnormal mineral metabolism but also with immune abnormalities. This study investigated the relationship between thyroid-specific autoantibodies and osteoporosis, including the bone mineral density (BMD) values and fractures. Methods: A retrospective analysis was conducted using data from the National Health and Nutrition Examination Survey (2007–2010). BMD was compared in different thyroid-specific autoantibodies groups. The associations between thyroid-specific autoantibodies and fractures were explored. Strengths of associations were calculated by binary logistic regression models. Candidate variables for binary logistic regression model were selected after screened in univariate analysis (variables with P < 0.05). Results: A total of 3865 study participants were included in this analysis; 224 participants were TgAb positive and 356 were TPOAb positive. A total of 392 participants reported hip, spine or wrist fractures. Participants with higher prevalence of TgAb or TPOAb had lower BMD. In females, significant cigarettes use, higher prevalence of TgAb and TPOAb, and the BMD of the total femur and femoral neck were significantly associated with fractures. Higher prevalence of TPOAb was particularly associated with a higher possibility of hip or spine fractures. In males, significant cigarettes use, 25OHD3, the BMD values of the total femur, femoral neck and total spine were significantly associated with fractures. Conclusion: Higher prevalence of thyroid-specific autoantibodies may lead to decreased BMD. In females, higher prevalence of TgAb and TPOAb significantly associated with fractures and TPOAb especially relating to the fractures of hip and spine. Males patients with vitamin D deficiency or insufficiency associated a higher possibility of fractures. [ABSTRACT FROM AUTHOR]

CAR T cell therapy has shown promising results in the treatment of autoimmune diseases. In 2023, five key studies were highlighted that are driving the development of CAR T cells to improve precision, safety, efficacy, and accessibility for the treatment of autoantibody-associated autoimmune diseases. CAR T cells targeting CD19 have been successful in achieving drug-free remission in patients with systemic lupus erythematosus. Other studies have explored the use of CAR T cells targeting B cell maturation antigen (BCMA) and chimeric autoantibody receptor (CAAR) T cells targeting specific autoantibodies in diseases such as neuromyelitis optica spectrum disorder and myasthenia gravis. Additionally, advancements have been made in the use of RNA-based CAR T cells, which offer potential advantages over DNA-based CAR T cells. These developments in precision cellular therapy hold promise for improving outcomes in autoimmune disease treatment. [Extracted from the article]

Serological tests are important to detect autoantibodies (autoAbs) in patients with autoimmune neuropathies (AN) and myasthenia gravis (MG) as they are biomarkers for diagnosis, stratification, treatment selection, and monitoring. However, tests to detect autoAbs frequently lack proper standardization and results differ across diagnostic laboratories. We compared results for tests routinely performed in Spanish diagnostic laboratories to detect AN and MG autoAbs. In the Spanish Society of Immunology Autoimmunity Group national workshop, serum samples from 13 patients with AN or MG were tested for anti-ganglioside, anti-myelin-associated glycoprotein (MAG), anti-nicotinic acetylcholine receptor (AChR), and anti-muscle-specific kinase (MuSK) autoAbs using reference methods and were distributed for analysis to 27 participating laboratories using their routine methods. Overserved were inter-laboratory variability and worryingly low sensitivity, especially for anti-ganglioside immunoglobulin G and anti-MAG autoAb detection. This pilot study reflects autoAbs detection state of the art in AN and MG testing in leading diagnostic laboratories in Spain, highlighting the need for standardization prior to clinical use. [ABSTRACT FROM AUTHOR]

Childhood-onset systemic lupus erythematosus (cSLE) is a chronic autoimmune disease with a multisystemic involvement diagnosed during childhood. The disease is marked by the production of autoantibodies targeting self-antigens, often before symptoms emerge. The presentation, clinical course, and outcome vary significantly among patients with cSLE. The onset of cSLE can be at any age during childhood while a diagnosis of cSLE before the age of 5 years is rare and raises a suspicion of monogenic lupus. Childhood-onset systemic lupus erythematosus affects various organs and systems, most frequently presenting with mucocutaneous, musculoskeletal, renal, and neuropsychiatric manifestations. Multiple disease flares can be seen during the disease course. Childhood-onset systemic lupus erythematosus causes significant morbidity and mortality. Children and adolescents with cSLE show higher disease activity and damage, and more aggressive immunosuppressive treatments are needed compared to adultonset SLE. Early diagnosis can be difficult due to the insidious onset with nonspecific symptoms. Disease activity and damage measures aim to ensure an accurate evaluation of disease status. A multidisciplinary approach and individualized disease management are important. Disease management is complex including the control of disease activity, the reduction of flares and damage, and a limitation of drug toxicity while improving the health-related quality of life in patients with cSLE. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case underscores the critical importance of timely recognition and management of NMDAR encephalitis in adolescents to mitigate potential long‐term sequelae. If a pediatric patient presents with suspected viral encephalitis, autoimmune etiology must be excluded via cerebrospinal fluid antibody assay to guide appropriate immunosuppressive therapy, and improve patient outcomes. Autoimmune encephalitis particularly involving the n‐methyl‐d‐aspartate receptor (NMDAR) is recognized as a rare cause of acute encephalopathy in pediatric patients. The following case is of a 14‐year‐old female diagnosed with anti‐NMDAR encephalitis who initially presented with fever, episodic convulsions, and loss of consciousness. She subsequently developed right‐sided body weakness, expressive aphasia, and visual hallucinations. Clinical examination revealed prominent neuropsychiatric manifestations such as altered sensorium, motor deficits, hallucinations, and visual disturbances. Cerebello‐bulbar signs were not appreciable in this particular case. She was treated for viral encephalitis but showed no improvement. Laboratory investigations revealed the presence of NMDAR antibodies in the cerebrospinal fluid confirming the diagnosis of autoimmune etiology. The patient demonstrated notable improvement following immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris (PV) is a rare autoimmune bullous dermatosis (AIBD) characterized by painful blistering of the skin and mucosa caused by autoantibodies that lead to loss of adhesion in the epidermis. Standard therapy for PV is corticosteroids, either alone or in combination with steroid-sparing immunosuppressants or infusions with rituximab. According to the published European guideline, high-dose intravenous immunoglobulin (IVIg) therapy with a dosage of 2 g per kg body weight distributed over 2–5 days every 4 weeks is a promising treatment option, especially for severe or refractory disease. This report describes a 73-year-old female patient with severe and recurrent disease who achieved stabilization with IVIg treatment. However, the patient experienced side effects such as headaches, nausea, and vomiting, which affected daily life. Hence, she was transitioned to a new IVIg preparation with a new manufacturing process, resulting in fewer side effects and an improved quality of life. Further follow-up is necessary to fully evaluate the effectiveness and tolerability of this new IVIg product. [ABSTRACT FROM AUTHOR]

The 16th non‐collagenous domain (NC16A) of BP180 is the main antigenic target of autoantibodies in bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP). Commercially available assays detect serum autoantibodies against NC16A in the majority of BP (80%–90%) and in approximately 50% of MMP patients. However, a standardized test system for detecting antibodies against other regions of BP180 is still lacking. Moreover, anti‐BP180 autoantibodies have been found in neurological conditions such as multiple sclerosis and Parkinson disease. This study aimed at identifying primary epitopes recognized by BP autoantibodies on the BP180 ectodomain. Serum samples of 51 BP and 30 MMP patients both without anti‐NC16A reactivity were included along with 44 multiple sclerosis and 75 Parkinson disease sera. Four overlapping His‐tagged proteins covering the entire BP180 ectodomain (BP180(ec)1–4) were cloned, expressed, purified and tested for reactivity by immunoblot. IgG antibodies to BP180(ec)3 were detected in 98% of BP, 77% of MMP and 2% of normal human sera. Only weak reactivity was detected for neurological diseases against BP180(ec)1, BP180(ec)2 and BP180(ec)4, in 3%, 11% and 7% of tested multiple sclerosis sera, respectively. 8% of Parkinson disease sera reacted with BP180(ec)2 and 9% with BP180(ec)4. In conclusion, this study successfully identified epitopes recognized by BP autoantibodies outside the NC16A domain in pemphigoid diseases. These findings contribute to a better understanding of the immune response in BP and MMP with potential implications for a future diagnostic assay for NC16A‐negative pemphigoid patients. [ABSTRACT FROM AUTHOR]

Objective Diagnostic role of autoantibodies (AAb) as serological biomarkers has not been specifically investigated in laryngeal cancer (LC) previously. The study investigates the presence of anti-LC AAbs and their potential as a biomarker for early diagnosis of LC, to improve patient outcome. Method Anti-LC AAb levels were investigated in LC patients (n = 30) and healthy individuals (n = 30) by indirect enzyme-linked immunosorbent assay (ELISA). Patient AAb levels were analyzed with various clinical factors, primarily tumor stage. Results AAb levels were significantly higher in LC patients than in the control group (P =.019). The diagnostic performance of AAb-level testing for LC detection presented a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 70% each. The positive likelihood (LR+) and negative likelihood (LR−) ratios were 2.33 and 0.43, respectively. AAb levels were independent of cancer stage (P =.708), duration since first appearance of symptoms (P =.228), duration of medical attention (P =.231), and degree of risk-factor exposure (P =.478). Conclusion Significant level of AAbs could be detected among LC patients with good diagnostic performance, irrespective of stage. Thus, anti-LC AAbs reflect potential to be utilized as predictive biomarkers in early diagnostics of LC. [ABSTRACT FROM AUTHOR]

Background Hashimoto's thyroiditis (HT) is an autoimmune disease that is frequently associated with other autoimmune conditions. Objective To perform serological screening for rheumatoid arthritis (RA) in patients with HT. Methods Our study included 88 consecutive serum specimens of patients with confirmed HT and 88 sex- and age-matched healthy subjects. All study participants were tested for anti-cyclic citrullinated peptides antibodies (CCP-Ab) and rheumatoid factor (RF). CCP-Ab and RF were performed using ELISA commercial kits. Statistical analysis was conducted using Epi Info, version 3. Results Out of 88 patients with HT, 15 (17.0%) had CCP-Ab or RF. The frequency of serological markers of RA was significantly higher in patients than in control individuals (17.0% vs 4.5%; P =.007). RF was more frequent in patients than in the control group, and the difference was statistically significant (13.6% vs 3.4%; P =.01). Isolated RF-IgM was absent in all controls and present in 6 patients with HT (6.8% vs 0%; P =.02). Out of 14 male patients, 3 (21.4%) had antibodies of RA. There was no significant difference in age between patients with CCP-Ab or RF and those without. Conclusion A high frequency of serological markers of RA was highlighted in patients with HT. [ABSTRACT FROM AUTHOR]

This study aims to analyze the clinical and immunologic features of SLE in Jordan, while also investigating the impact of age and gender on disease presentation. The study included 275 patients diagnosed with SLE. Data were collected through meticulous patient interviews and thorough examination of patient hospital records. The cohort exhibited a mean age of 36.8 ± 12.9 years, with an average disease duration of 7.0 ± 7.8 years. The mean age at diagnosis was 29.9 ± 12.1 years, and the female to male ratio was 7.8:1. The most frequently observed symptoms were arthralgia (90.2%), fatigue (80.7%), hematologic manifestations (62%), photosensitivity (60.7%), Raynaud's phenomenon (53.5%), and malar rash (50.9%). The frequencies of various autoantibodies were as follows: ANA (96.7%), anti-dsDNA (39.6%), anti-SSA/Ro (32.8%), anti-Sm (21.8%), anti-U1-RNP (20.6%), and anti-SSB/La (15.5%). Male patients tended to receive a diagnosis at a younger age and exhibited a higher likelihood of experiencing severe manifestations compared to females. Additionally, juvenile onset patients demonstrated an increased likelihood of fever, photosensitivity, myositis, and anti-dsDNA autoantibodies, while adult onset patients were more predisposed to having anti-Ro, anti-La, and RF autoantibodies. This study reveals that the most prevalent manifestations of SLE in the Jordanian cohort encompassed arthralgia, fatigue, and hematologic manifestations. The prevalence of alopecia and Raynaud's phenomenon exceeded that observed in other published cohorts, while arthritis and discoid rash were less frequently encountered. The study highlights that males are more susceptible to developing severe manifestations of SLE compared to females. [ABSTRACT FROM AUTHOR]

This study was aimed at assessing the diagnostic significance of Anti-ACTC1, Anti-MYH7B, and Anti-cTnI autoantibodies at the molecular level, as well as their relationship with the results of electrocardiography in predicting damage to the heart muscle in athletes under conditions of physical stress. A medical examination was conducted on 35 men aged 8 to 25 years divided into 2 groups: proffessional basketball players and participants with the usual amount of total motor activity. The study included consultation with medical specialists, physical development research; psychological questionnaires; laboratory screening; and instrumental diagnostics. The values of blood parameters in athletes exceed the reference intervals: the content of erythrocytes by 15.8%, hemoglobin by 11.25%, and hematocrit by 9.1%. The concentration of testosterone in athletes is within the normal range, but during training, it can decrease by 35.5%, indicating anabolism and muscle growth, or overstrain or negative factors. It was found intense stress and emotional stress can cause myocardial stress, microtrauma, and inflammation in the heart muscles, stimulating the immune response and expression of serum antibodies anti-ACTC1, anti-MYH7B, anti-cTnI, as a result of pathophysiological remodeling of the myocardium. [ABSTRACT FROM AUTHOR]

The ZnT8 autoantibody is used to independently diagnose type 1 diabetes (T1D) and as a prediction factor in high-risk populations. This is the first report in Taiwan on the prevalence, diagnostic utility, and clinical characteristics of zinc transporter 8 autoantibody (ZnT8A) in children with T1D. We performed a retrospective analysis of 268 children (130 boys, 138 girls) newly diagnosed with T1D at three hospitals in North Taiwan from February 1994 to August 2021. ZnT8A was detected in 117 patients (43.7 %). The combined diagnostic rate of the four antibodies, including glutamic acid decarboxylase autoantibody (GADA), islet antigen 2 autoantibody (IA2A), insulin autoantibody (IAA), and ZnT8A, can reach 86.19 % while that of the original three antibodies is 84.3 %. IA2A (64.9 %) showed the highest positive rate, followed by GADA (64.2 %), ZnT8A (43.7 %), and IAA (22.0 %). Of the 268 patients, five (1.9 %) were only ZnT8A+. All antibodies were positive in 19 (7.1 %) people, whereas 37 others (13.8 %) had all antibodies negative. ZnT8A has the strongest relationship with IA2A. 5 patients had ZnT8A positive only. 5/(37 + 5) (about 12 %) T1D patients were diagnosed by ZnT8A testing. ZnT8A testing can diagnose up to 12 % more patients with T1D along with three other antibodies. Furthermore, since the ZnT8A titer decreased over time, it should be tested within six months of onset in Taiwanese patients with T1D. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)