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Background: Adhesion molecule CD44 contributes to T cell migration into target organs. A higher expression of CD44v3 and v6 isoforms has been identified on T cells from systemic lupus erythematosus (SLE) patients. The aim of this study was to investigate the expression of CD44v3/v6 on T cells of SLE patients in order to evaluate their correlation with clinical features. Methods: Sixteen healthy subjects (HSs) and 33 SLE female patients were enrolled. Fifteen patients were in remission (Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) = 0) and 18 patients had an active disease (SLEDAI-2K ≥ 4). Experiments were conducted by flow cytometry. Results: Expression of CD44v3 on CD4+ and CD8+ T cells was higher in active patients compared to HSs (p = 0.0097 and p = 0.0096). CD44v3 on CD8+ T cells was also higher in active patients compared to patients in remission (p = 0.038). CD44v6 was higher on CD4+ and CD8+ T cells from active patients compared to HSs (p = 0.003 and p = 0.0036) and to patients in remission (p = 0.01 and p = 0.02). In active patients the ratio CD44v3/v6 was unbalanced towards isoform v6 on both T cell populations. In a receiver operating characteristic curve analysis, CD44v6 on CD4+ T cells was the most sensitive and specific one (specificity of 81.8%, sensitivity of 75%). Expression of CD44v6 on CD4+ and CD8+ T cells correlated with the SLEDAI-2K (p = 0.03, r = 0.38 and p = 0.02, r = 0.39). CD44v6 and CD44v3 on CD8+ T cells associated with nephritis and arthritis (p = 0.047 and p = 0.023). Conclusions: CD44v3/v6 can be used as biomarkers of disease activity and phenotypes; isoform v6 on CD4+ T cells can be useful as a diagnostic biomarker. [ABSTRACT FROM AUTHOR]

Specific indices are not available to evaluate systemic lupus erythematosus (SLE) joint involvement; indeed, the application of indices validated for rheumatoid arthritis has been suggested. We evaluated the usefulness of organ specific composite indices, i.e. the Disease Activity Score on 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and the ratio of swollen to tender joints (STR), to assess SLE joint activity by analyzing the correlation between these indices and ultrasonography (US) inflammatory status. We evaluated SLE patients with arthralgia and/or arthritis: the above-mentioned indices were calculated and the SLE Disease Activity Index 2000 (SLEDAI-2k) was applied to assess global disease activity. US of I–V metacarpophalangeal, I–V proximal interphalangeal, wrist, and knee bilateral was performed. Synovial effusion/hypertrophy and power Doppler findings were scored according to a semi-quantitative scale (0–3) to obtain an inflammatory total score (0–216). One hundred and six patients (M/F 7/99, median age 49.5 years (IQR 17.0), median disease duration 8.5 years (IQR 17.0)) were enrolled. We identified a positive correlation between US score and DAS28-CRP (r = 0.3, p = 0.007), STR (r = 0.42, p = 0.0005), SDAI (r = 0.33, p = 0.02), CDAI (r = 0.29, p = 0.03); US score reflected different levels of clinimetric joint activity. In conclusion, we suggest the ability of composite indices in detecting SLE joint inflammation and their possible real-life use. [ABSTRACT FROM AUTHOR]

This longitudinal retrospective study aims at describing the safety profile and the reasons for discontinuation of antimalarials in patients with systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE), focusing on ocular toxicity. We analyzed the clinical data of 845 SLE and DLE patients; 59% of them were taking antimalarials: 1.4% chloroquine (CQ), 88.5% hydroxychloroquine (HCQ) and 10.1% both. The mean therapy duration was 82.5 ± 77.4 months. At least one side effect was reported by 19.4% of patients, leading to temporary or permanent withdrawal in 9.1% and 10.3% of cases, respectively; 19.3% of patients experienced side effects with HCQ and 8.6% with CQ. In 55.1% of cases, the adverse event was mild or moderate. Ophthalmological alterations were reported by 8.5% but were confirmed by the ophthalmological examination in 5.5% of cases. Retinal alterations were associated with age, disease duration and duration of the antimalarial therapy, but not to drug dose and comorbidities or lupus nephritis. This is the largest monocentric longitudinal study confirming the good safety profile of antimalarials in DLE and SLE patients. The main adverse events during the therapy were mild or moderate, but maculopathy-reported in a low percentage of patients-remains the main cause of treatment withdrawal. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a common heterogeneous autoimmune disease that is caused by the involvement both of genetic and environmental factors. There is evidence that autophagy is involved in several aspects of SLE pathogenesis. In particular, polymorphisms in the ATG5 gene have been observed to be associated with disease susceptibility. Our aim was to verify if ATG5 polymorphisms are involved in the susceptibility to disease and its clinical phenotypes in an Italian cohort of SLE patients. This study involved 315 SLE patients and 265 healthy controls. Three polymorphisms in the ATG5 gene (rs573775, rs6568431 and rs2245214) were investigated by allelic discrimination assay. A case-control association study, a genotype/phenotype correlation analysis and a haplotype study were performed. Moreover, an expression study was conducted in peripheral blood mononuclear cells from 15 SLE patients to verify a possible effect of the three SNPs on the expression of ATG5. Among the three investigated SNPs, only the rs573775 SNP was significantly associated with disease susceptibility with the variant allele conferring a higher risk of developing SLE (OR=1.50, p=0.018 and OR=1.48, p=0.007 at the genotypic and allelic level, respectively). The variant allele of rs6568431 SNP was more present in patients with anemia (OR=1.86, p=0.009) and renal involvement (OR=1.63, p=0.06), while the variant allele of rs2245214 SNP was significantly associated with a higher risk of producing anti-DNA autoantibodies (OR=1.66, p=0.04). Carriers of the rs6568431 variant allele showed higher messenger RNA levels compared to the carriers of the wild-type allele, suggesting also a potential variant allele dose-dependent effect on gene expression. In conclusion, our study confirms a role for ATG5 polymorphisms both in disease susceptibility and in the modulation of clinical phenotypes in an Italian SLE cohort. These results further suggest that genetic variations in autophagy genes could play a role in autoimmune diseases susceptibility and are worth further investigation. [ABSTRACT FROM AUTHOR]

Objective Several studies have evaluated the prevalence of rheumatoid factor (RF) and anti-citrullinated proteins antibodies (ACPA) in systemic lupus erythematosus (SLE) patients but no data are available on the anti-carbamylated proteins (anti-CarP), a new biomarker for rheumatoid arthritis (RA). We evaluated the anti-CarP prevalence in SLE patients with joint involvement and the associations with different phenotypes. Methods Seventy-eight SLE patients with joint involvement were enrolled (F/M 73/5; mean ± SD age 47.6 ± 11.2 years; mean ± SD disease duration 214.3 ± 115.6 months). As control groups, we evaluated SLE patients without joint manifestations (N = 15), RA (N = 78) and healthy individuals (HS, N = 98). Anti-CarP were assessed by home-made ELISA in all patients and controls, RF and ACPA in SLE patients with joint involvement (commercial ELISA kit). Results The prevalence of anti-CarP in SLE patients with joint involvement was similar to RA (p = NS) and significantly higher compared with SLE without joint involvement and HS (p < 0.0001, p < 0.0001, respectively). Four patients were positive for all three antibodies: seventy-five percent of these showed Jaccoud arthropathy. Fourty-five percent of ACPA-ve/RF-ve patients were anti-CarP + ve. Conclusions The evaluation of anti-CarP in SLE joint involvement demonstrated a prevalence of almost 50%, similar to RA and significantly higher than SLE without joint involvement and HS. [ABSTRACT FROM AUTHOR]

Recently, a study has shown that a polymorphism in the region of MIR1279 modulates the expression of the TRAF3IP2 gene. Since polymorphisms in the TRAF3IP2 gene have been described in association with systemic lupus erithematosus (SLE) susceptibility and with the development of pericarditis, our aim is to verify if the MIR1279 gene variability could also be involved. The rs1463335 SNP, located upstream MIR1279 gene, was analyzed by allelic discrimination assay in 315 Italian SLE patients and 201 healthy controls. Moreover, the MIR1279 gene was full sequenced in 50 patients. A case/control association study and a genotype/phenotype correlation analysis were performed. We also constructed a pericarditis genetic risk profile for patients with SLE. The full sequencing of the MIR1279 gene in patients with SLE did not reveal any novel or known variation. The variant allele of the rs1463335 SNP was significantly associated with susceptibility to pericarditis (P = 0.017 and OR = 1.67). A risk profile model for pericarditis considering the risk alleles of MIR1279 and three other genes (STAT4, PTPN2 and TRAF3IP2) showed that patients with 4 or 5 risk alleles have a higher risk of developing pericarditis (OR = 4.09 with P = 0.001 and OR = 6.04 with P = 0.04 respectively). In conclusion, we describe for the first time the contribution of a MIR1279 SNP in pericarditis development in patients with SLE and a genetic risk profile model that could be useful to identify patients more susceptible to developing pericarditis in SLE. This approach could help to improve the prediction and the management of this complication. [ABSTRACT FROM AUTHOR]

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) has been widely described in many studies conducted thus far. The syndrome incorporates five immunemediated conditions, all associated with previous exposure to various agents such as vaccines, silicone implants and several others. The emergence of ASIA syndrome is associated with individual genetic predisposition, for instance those carrying HLA-DRB1*01 or HLA-DRB4 and results from exposure to external or endogenous factors triggering autoimmunity. Such factors have been demonstrated as able to induce autoimmunity in both animal models and humans via a variety of proposed mechanisms. In recent years, physicians have become more aware of the existence of ASIA syndrome and the relationship between adjuvants exposure and autoimmunity and more cases are being reported. Accordingly, we have created a registry that includes at present more than 300 ASIA syndrome cases that have been reported by different physicians worldwide, describing various autoimmune conditions induced by diverse adjuvants. In this review, we have summarized the updated literature on ASIA syndrome and the knowledge accumulated since 2013 in order to elucidate the association between the exposure to various adjuvant agents and its possible clinical manifestations. Furthermore, we especially referred to the relationship between ASIA syndrome and systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). [ABSTRACT FROM AUTHOR]

Objectives Literature data suggest a significantly higher mortality in patients affected by systemic lupus erythematosus (SLE) developing chronic damage. Therefore, damage prevention is a major goal in the management of SLE patients. In the present study, we assessed damage by means of the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI), in a large cohort of SLE patients. Additionally, we aimed at evaluating its association with demographic and clinical features as well as with disease activity and laboratory findings. Patients and methods We enrolled consecutive patients affected by SLE diagnosed according to the American College of Rheumatology (ACR) 1997 revised criteria. Chronic damage was determined by SDI calculated at the last examination in all patients with at least six months of follow-up. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K); flare was defined as an increase of SLEDAI-2K ≥ 4 compared with the previous visit. Results We evaluated 349 SLE patients (M/F 25/324, mean age ± SD 42.7 ± 12.4 years, mean disease duration ± SD 164.9 ± 105.2 months). Among the enrolled patients, 125 (35.8%) showed a SDI ≥ 1 (mean SDI ± SD 1.7 ± 0.9, range 0–5). The musculo-skeletal was the most frequently involved organ/system in SDI score (41/349 patients, 11.7%), with deforming/erosive arthritis in 21/349 (6.0%). The presence of chronic damage was associated with age (P < 0.001), disease duration (P < 0.001), number of flares (P = 0.02) and with the use of glucocorticoids (P = 0.02). The logistic regression analysis revealed the association between neuropsychiatric damage and antiphospholipid syndrome (P = 0.01, OR = 3.9) and between the presence of cardiovascular damage and anti-β2GPI antibodies (P = 0.01, OR 6.2). Conclusions In the present study chronic damage was identified in about one third of SLE patients. The association between SDI and the number of flares claim for a thigh-control of the disease activity in order to prevent the chronic damage. The possible role of antiphospholipid antibodies (aPL) in the development of neuropsychiatric and cardiovascular damage may suggest a more careful assessment of such aPL positive patients. [ABSTRACT FROM AUTHOR]

The article examines the validity of a linguistically validated version of the Lupus Quality of Life (LupusQoL) in adult Italian patients affected by systemic lupus erythematosus (SLE). The Italian version of the LupusQoL and the Short Form (SF)-36 is completed by consecutive SLE patients. It found that the Italian version of the LupusQoL is a useful tool for adult patients with SLE.

Immune thrombocytopaenic purpura (ITP) is an autoimmune systemic disease detectable by the presence of low blood platelets count (<105/µl) and the production of autoantibodies against glycoproteins expressed on the platelet surface. The clinical course is often acute, and life-threatening events may occur especially in children, with 52% of paediatric patients recovering either spontaneously or after treatment. A chronic ITP evolution is observed in 64% of adults, of whom 12% will develop an overlapping autoimmune disease.Several microbial agents such as CagA-positive Helicobacter pylori or Candida albicans and a number of viruses including CMV, EBV or HIV can potentially trigger ITP through molecular mimicry. Moreover, ITP improves after treatment of the underlying infection. Similarly, vaccines such as MMR may prompt ITP (IRR 5.48, 1.61–18.64, p < 0.006).Early recognition of the underlying microbial trigger and the removal of modifiable aetiopathogenetic factors should be integrated as a complementary treatment strategy in all patients who do not readily improve with standard ITP care. [ABSTRACT FROM PUBLISHER]