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Introduction: Antiphospholipid syndrome (APS) manifests with thrombosis and pregnancy losses and may significantly impair the health-related quality of life (HRQoL). So far, APS has been perceived as a less burdensome disease than systemic lupus erythematosus (SLE), but data on this are scarce. The purpose of the present study was to evaluate HRQoL in APS patients by applying the Short Form 36 Health Survey (SF-36) and World Health Organization Quality-of-Life Scale (WHOQoL-BREF); to examine the impact of primary APS and with coexisting SLE (APS/SLE) on patient HRQoL; and to provide a description of the APS patient population., Material and Methods: One hundred twelve patients with APS were included in the study, 57 of them with primary APS and 55 with coexisting SLE. HRQoL was measured by the 36-Item SF-36 and WHOQoL questionnaires., Results: Mean age was 47 years (47.6 ±13.8), and 96 patients were (85.7%) women. The mean disease duration was 72 months. Health-related quality of life impairment was found in both components for all APS patients in comparison to the healthy Polish population ( p < 0.0001). There was no difference between APS and APS/SLE groups in HRQoL (mental component p = 1.0, physical component p = 0.337). The history of venous thrombosis was associated with HRQoL impairment only in the APS/SLE group in the physical component ( p = 0.0118), not in primary APS ( p = 0.6862). The mental component of SF-36 was associated with all domains of WHOQoL-BREF, while the physical component was associated only with physical health ( p < 0.001)., Conclusions: Primary APS and APS secondary to SLE lead to equal impairment in HRQoL. Diagnosis and proper management of all patients with APS are essential to prevent thrombosis and miscarriages, which ultimately will lead to longer survival with optimal life quality., Competing Interests: Ewa Haladyj since June 2017 has been an employee and shareholder of Eli Lilly and Co., but at the time of this research she was an employee of the National Institute of Geriatrics, Rheumatology and Rehabilitation in Warsaw. Agata Wieczorek, Tomasz Wysocki and Marzena Olesinska do not state any conflict of interest., (Copyright: © 2024 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.)

Recent studies have shown that people who are immunocompromised may inadvertently play a role in spurring the mutations of the virus that create new variants. This is because some immunocompromised individuals remain at risk of getting COVID-19 despite vaccination, experience more severe disease, are susceptible to being chronically infected and remain contagious for longer if they become infected and considering that immunocompromised individuals represent approximately 2% of the overall population, this aspect should be carefully considered. So far, some autoimmune rheumatic disease (ARD) patients with COVID-19 have been treated with antiviral therapies or anti-SARS-CoV-2 antibody products. However, there is no homogeneous approach to these treatment strategies. This issue was addressed within the European Reference Network (ERN) on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET) in a discussion among experts and patient's representatives in the context of the rare and complex connective tissue diseases (rCTDs) covered by the Network. ERN ReCONNET is one of the 24 ERNs launched by the European Commission in 2017 with the aim of tackling low prevalence and rare diseases that require highly specialised treatment and promoting concentration of knowledge and resources through virtual networks involving healthcare providers (HCPs) across the European Union (EU). Considering the urgent need to provide guidance not only to the rCTDs community, but also to the whole ARDs community, a multidisciplinary Task Force, including expert clinicians and European Patient Advocacy Group (ePAG) Advocates, was created in the framework of ERN ReCONNET with the aim of developing overarching principles (OP) and points-to-consider (PtC) on a homogenous approach to treat immunocompromised patients with ARDs (with a particular focus on CTDs) affected by COVID-19 using antiviral therapies and anti-SARS-CoV-2 antibody products. The present work reports the final OP and PtC agreed by the Task Force.

Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease, and IL-1β, IL-10, and TNF-α genes are important in the pathogenesis of this disease. We studied the impact of IL-1β-511, IL-1β +3953, IL-10 -592, IL-10 -1082, TNF-α -308, TNF-α -238, and TNF-α +489 polymorphisms on SLE risk and phenotype in SLE patients and healthy controls., Methods: We genotyped SLE patients and healthy controls by real-time PCR on QuantStudio 5 (Applied Biosystems) and measured levels of cytokines by enzyme-linked immunosorbent assay (ELISA)., Results: We indicated that TNF-α -308, IL-10 -592, IL-10 -1082, IL-1β-511 and IL-1β +3953 polymorphisms affect SLE risk. Furthermore, we exposed that some of the TNF-α +489, TNF-α -238, IL-10 -1082 and IL-1β +3953 genotypes are connected with the SLE phenotype. Moreover, we discovered the linking between specific genotypes and the serum concentrations of TNF-α, IL-1β, and IL-10., Conclusions: In conclusion, our study revealed that IL-1β-511, IL-1β +3953, IL-10 -592, IL-10 -1082, and TNF-α -308 polymorphisms may affect SLE risk and phenotype.

Neonatal lupus erythematosus (NLE) is a syndrome of clinical symptoms observed in neonates born to mothers with antibodies to soluble antigens of the cell nucleus. The main factors contributing to the pathogenesis of this disease are anti-Sjögren Syndrome A (anti-SS-A) antibodies, known as anti-Ro, and anti-Sjögren Syndrome B (anti-SS-B) antibodies, known as anti-La. Recent publications have also shown the significant role of anti-ribonucleoprotein antibodies (anti-RNP). Seropositive mothers may have a diagnosed rheumatic disease or they can be asymptomatic without diagnosis at the time of childbirth. These antibodies, after crossing the placenta, may trigger a cascade of inflammatory reactions. The symptoms of NLE can be divided into reversible symptoms, which concern skin, hematological, and hepatological changes, but 2% of children develop irreversible symptoms, which include disturbances of the cardiac stimulatory and conduction system. Preconceptive care and pharmacological prophylaxis of NLE in the case of mothers from the risk group are important, as well as the monitoring of the clinical condition of the mother and fetus throughout pregnancy and the neonatal period. The aim of this manuscript is to summarize the previous literature and current state of knowledge about neonatal lupus and to discuss the role of anti-Ro in the inflammatory process.

Dysregulation in type I IFN and IFN-stimulated genes (ISGs) induced by monocytes is one of the key features of systemic sclerosis (SSc) pathogenesis. Abnormalities in microRNA (miRNA) expression are related to excessive IFN production, however the role of miRNA remains largely elusive in SSc monocytes. This study explores global miRNA-mRNA profiling of SSc monocytes and functional attenuation of IFN and ISGs by specific miRNAs. Global sequencing of mRNA (mRNA-seq) and miRNA (miRNA-seq) samples were performed simultaneously on healthy controls and SSc monocytes. Following computational analysis, selected miRNAs-mRNA candidates were validated, correlated with clinical parameters, and tested by functional assays. Transcriptomics data and qPCR analysis confirmed IFN signature in SSc but not in rheumatoid arthritis monocytes. Based on miRNA-seq analysis, five miRNAs were selected for further validation. Only the expression patterns of miRNA-26a-2-3p and miRNA-485-3p were confirmed and negatively correlated with clinical parameters. Exogenous delivery of miRNA-26a-2-3p to TLR-stimulated monocytic THP-1 cells specifically inhibited ISGs but not inflammasome activity in functional assays. In conclusion, our miRNA-mRNA co-sequencing and functional analysis identify miRNA-26a-2-3p as a new candidate, which is predicated to negatively regulate ISGs. This implies that reduced expression of miRNA-26a-2-3 may be involved in pathogenic IFN signature in SSc monocytes., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Systemic lupus erythematosus (SLE) is a chronic and systemic autoimmune disease. SLE is described by production of autoantibodies and causes damage of many organs. T-cells play a crucial role in SLE pathogenesis. T-cells intensify inflammation through a number of processes, which leads to autoimmunization. CCR5 and MECP2 genes are linked with T-cells and pathogenesis of SLE. Polymorphisms in these genes are related with the prognostic factors of risk of disease onset and disease severity. The aim of this study was to estimate the influence of polymorphisms in MECP2 and CCR5 genes on the development and course of systemic lupus erythematosus. We examined 137 SLE patients and 604 healthy controls. We studied polymorphisms for CCR5 gene: rs333 and for MECP2: rs2075596, rs1734787, rs17435, and rs2239464. We genotyped our MECP2 samples and we performed a restriction fragment length polymorphism (RFLP) analysis for CCR5 samples. We showed a risk factor for allele T in rs17435 and for allele A in rs2075596 in MECP2. We noticed that MECP2 rs2075596 G/A, rs1734787 C/A, rs17435 A/T, and rs2239464 G/A polymorphisms are more prevalent in SLE patients than in healthy controls. We believe that above-mentioned MECP2 polymorphisms can be considered as SLE susceptibility factor., Competing Interests: The authors declare no conflict of interest.

Mixed connective tissue disease (MCTD) is a rare disorder characterized by symptoms that overlap two or more Autoimmune Connective Tissue Diseases (ACTDs). The aim of this study was to determine whether miRNAs participating in the TLRs signaling pathway could serve as biomarkers differentiating MCTD or other ACTD entities from a healthy control group and between groups of patients. Although the selected miRNA expression level was not significantly different between MCTD and control, we observed that miR-126 distinguishes MCTD patients from all other ACTD groups. The expression level of miRNAs was significantly higher in the serum of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients compared to controls. The miR-145 and -181a levels distinguished RA from other ACDT patients. miR-155 was specific for SLE patients. MiR-132, miR-143, and miR-29a distinguished RA and SLE patients from the systemic sclerosis (SSc) group. Additionally, some clinical parameters were significantly related to the miRNA expression profile in the SLE group. SLE and RA are characterized by a specific serum expression profile of the microRNAs associated with the Toll-like receptors (TLRs) signaling pathway. The analysis showed that their level distinguishes these groups from the control and from other ACTD patients. The present study did not reveal a good biomarker for MCTD patients., Competing Interests: The authors declare no conflict of interest.

Objectives: The aim of the study was to explore whether TGF-β and IL-6 gene polymorphisms may be associated with SLE and assess the frequency of HLA-DRB1 alleles in Polish systemic lupus erythematosus (SLE) patients., Methods: 216 SLE patients and 552 healthy individuals were examined for TGF-β rs1800469 and rs1800470 by TaqMan SNP genotyping assay and for and IL-6(rs2069827 and rs1800795 using the PCR- RFLP method., Results: An increased frequency of TT genotype and T allele of the TGF β -509 C/T was found in SLE patients (p=0.02). The TGF-β 869 C allele was more frequent in SLE patients. The genotype-phenotype analysis showed association between the TGF β -509 C/T and mean value of CRP, ESR, haemoglobin, APTT, Pt and INR (p=0.05, p=0.03, p<0.001, p=0.03, p=0.03 and p=0.05, respectively) as well as anti-SSA and anti-Sm presence (p=0.04 and p=0.03, respectively); the TGF- β 869 T/C and mean value of APTT and INR (p=0.01 and p=0.05, respectively); the IL-6 -174 G/C and SLICC (p=0.05), anti-SSA (p=0.05) and anti-SSB (p=0.05). A higher TGF-β and IL-6 serum level were found in SLE patients compared to controls (both p<0.0001). In SLE patients with the TGF-β -509 TT genotype have shown positive association with the TGF-β serum levels. Polish SLE patients have strong positive association with HLA-DRB1*52.1, and negative with the HLA-DRB1*07:01 allele. HLA-DRB1*52.1 was also associated with higher TGF-β serum levels in the Polish population., Conclusions: Our results suggested that the TGF β -509 C/T variant may be considered as a genetic marker for SLE in the Polish population.

We investigated kinase insert domain-containing receptor (KDR) polymorphisms and protein levels in relation to susceptibility to and severity of Rheumatoid Arthritis (RA). 641 RA patients and 340 controls (HC) were examined for the rs1870377 KDR variant by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method and for rs2305948 and rs2071559 KDR single nucleotide polymorphisms (SNPs) by TaqMan SNP genotyping assay. KDR serum levels were determined by enzyme-linked immunosorbent assay (ELISA). The rs1870377 KDR variant has shown association with RA under the codominant ( p = 0.02, OR = 1.76, 95% CI = 1.09-2.85) and recessive models ( p = 0.019, OR = 1.53, 95% CI = 1.07-2.20). KDR rs2305948 was associated with RA under the dominant model ( p = 0.005, OR = 1.38, 95% CI = 1.10-1.73). Under the codominant model, the frequency of the rs2071559 TC and GG genotypes were lower in RA patients than in controls ( p < 0.001, OR = 0.51, 95% CI = 0.37-0.69, and p = 0.002, OR = 0.57, 95% CI = 0.39-0.81). KDR rs2071559 T and rs2305948 A alleles were associated with RA ( p = 0.001, OR = 0.60, 95% CI = 0.45-0.81 and p = 0.008, OR = 1.71, CI = 1.15-2.54). KDR rs2305948SNP was associated with Disease Activity Score (DAS)-28 score ( p < 0.001), Visual Analog Scale (VAS) score ( p < 0.001), number of swollen joints ( p < 0.001), mean value of CRP ( p < 0.001). A higher KDR serum level was found in RA patients than in HC (8018 pg/mL versus 7381 pg/mL, p = 0.002). Present results shed light on the role of KDR genetic variants in the severity of RA., Competing Interests: The authors declare that they have no conflict of interest.

Neutrophils are one of the first cells to arrive at the site of infection, where they apply several strategies to kill pathogens: degranulation, respiratory burst, phagocytosis, and release of neutrophil extracellular traps (NETs). Recent discoveries try to connect NETs formation with autoimmune diseases, like systemic lupus erythematosus (SLE) or granulomatosis with polyangiitis (GPA) and place them among one of the factors responsible for disease pathogenesis. The aim of the study was to assess the NETotic capabilities of neutrophils obtained from freshly diagnosed autoimmune patients versus healthy controls. Further investigation involved assessing NETs production among treated patients. In the latter step, NETs degradation potency of collected sera from non-treated patients was checked. Lastly, the polymorphisms of the DNASE I gene among tested subjects were checked. NETs formation was measured in a neutrophil culture by fluorometry, while degradation assessment was performed with patients' sera and extracellular source of DNA. Additionally, Sanger sequencing was used to check potential SNP mutations between patients. About 121 subjects were enrolled into this study, 54 of them with a diagnosed autoimmune disorder. Neutrophils stimulated with NETosis inducers were able to release NETs in all cases. We have found that disease affected patients produce NETs more rapidly and in larger quantities than control groups, with up to 82.5% more released. Most importantly, we showed a difference between the diseases themselves. NETs release was 68.5% higher in GPA samples when compared to SLE ones while stimulated with Calcium Ionophore. Serum nucleases were less effective at degrading NETs in both autoimmune diseases, with a reduction in degradation of 20.9% observed for GPA and 18.2% for SLE when compared with the controls. Potential therapies targeting neutrophils and NETs should be specifically tailored to the type of the disease. Since there are significant differences between NETs release and disease type, a standard neutrophil targeted therapy could prevent over-generation of traps in some cases, while in others it would deplete the cells, leaving the immune system unresponsive to primary infections.

Introduction: Rheumatoid arthritis (RA) is an autoimmune diseases, where different genetic variants in cytokine genes may play a pathogenic role. A GWAS in autoimmune diseases highlighted the IL-23R gene as a one of the susceptibility factors. We examined three candidate single nucleotide polymorphisms (SNPs) rs10889677, rs11209026 and rs2201841 of the IL-23R gene, as well as determined their possible association with RA in a Polish population., Patients and Methods: The IL-23R gene polymorphisms were genotyped for 422 RA patients and 348 healthy individuals using TaqMan SNP genotyping assay., Results: The genotypes frequency did not deviate from HWE in each examined group. A comparison of the allele as well as genotype frequencies of the IL-23R polymorphisms under codominant, dominant and recessive genetic model revealed no significant differences between RA patients and healthy subjects. We also demonstrated that IL-23R rs2201841 and rs11209026 as well as rs11209026 and rs10889677 were in complete linkage disequilibrium (D'=1.0). Our genotype-phenotype analysis demonstrated that in carriers of rs10889677C and/or rs2201841A allele the RF, extra-articular manifestations and erosion were more frequent present than in patients with rs10889677A and/or rs2201841A allele, although this association was not significant., Discussion: Present findings indicated that the autoimmune disease-associated genetic variants in IL-23R gene are not associated with RA in the Polish population., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Objectives: The aim of the study was to identify HIF-1A genetic variants and their possible association with HIF-1α, VEGF, KDR, RORc and Foxp3 protein levels, and susceptibility to and severity of RA., Methods: The HIF-1A gene polymorphisms were genotyped for 587 RA patients and 341 healthy individuals. The HIF-1α, VEGF, KDR, RORc and Foxp3serum levels were evaluated., Results: Under the codominant model, the frequency of the rs12434438 GG genotype was lower in RA patients than in controls (P = 0.02). Under the recessive model (AA + AG vs GG), the association was also significant (OR 3.32; CI 1.19-9.24; P = 0.02). Overall, rs12434438 A/G and rs1951795 A/C are in almost completed linkage disequilibrium with D' = 0.96 and r 2  = 0.85. The HIF-1A rs1951795 A allele was associated with rheumatoid factor (P = 0.02) and mean value of erythrocyte sedimentation rate (ESR) (P = 0.05). In RA patients with HIF-1A rs12434439 GG genotype, the parameters of disease activity such as DAS-28, VAS score, Larsen score or HAQ score were lower compared to RA patients with the HIF-1A rs12434439 AA genotype. Moreover, we also observed that Foxp3 serum levels were higher, and RORc2 serum levels were lower in RA patients with rs12434439 GG., Conclusion: The polymorphic HIF-1A rs12434439 GG genotype may play a protective role for RA development.

Systemic sclerosis (SSc) is an immune-mediated connective tissue disease of which the aetiology is still unclear. Previous genetic studies including candidate-gene studies and genomewide association studies have identified a number of genetic variations that confer risk to SSc. However, these variants, such as single nucleotide polymorphisms, cannot completely explain the SSc susceptibility and the diversity in the clinical symptoms of SSc patients. The contribution of epigenetic mechanisms as a link between genetics and environmental triggers represents promising field in understanding the pathogenesis of SSc. The aim of this review was to present the current knowledge on epigenetic mechanisms and highlight novel directions in diagnostic and therapeutical approaches., (© 2017 The Foundation for the Scandinavian Journal of Immunology.)

Objective: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups., Methods: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria., Results: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) "probable IIM," had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to "definite IIM." A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50-<55% as "possible IIM.", Conclusion: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of "definite," "probable," and "possible" IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria., (© 2017, American College of Rheumatology.)

Objective: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups., Methods: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria., Results: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) 'probable IIM', had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to 'definite IIM'. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as 'possible IIM'., Conclusions: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of 'definite', 'probable' and 'possible' IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria., Competing Interests: Competing interests: JAS has received research grants from Takeda and Savient and consultant fees from Savient, Takeda, Regeneron, Merz, Iroko, Bioiberica, Crealta and Allergan. JAS serves as the principal investigator for an investigator-initiated study funded by Horizon pharmaceuticals through a grant to DINORA, Inc., a 501 (c)(3) entity. JAS is a member of the executive committee of OMERACT, an organisation that develops outcome measures in rheumatology and receives arms-length funding from 36 companies; a member of the American College of Rheumatology’s (ACR) Annual Meeting Planning Committee (AMPC); Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee. HC and RGC’s work in myositis is partly funded by grants from Arthritis Research UK (18474) and the Medical Research Council (MR/N003322/1). JV’s work in myositis is supported by Project (Ministry of Health, Czech Republic) for conceptual development of research organization 00023728., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Inflammation and angiogenesis are a significant element of pathogenesis in rheumatoid arthritis (RA). The FLT-1- triggering factor for production of proinflammatory cytokines-might contributes to inflammation in patients with RA. Association of the FLT-1 polymorphisms with different "angiogenic diseases" suggests that it may be a novel genetic risk factor also for RA. The aim of the study was to identify FLT-1 genetic variants and their possible association with sFLT-1 levels, susceptibility to and severity of RA., Methods: The FLT-1 gene polymorphisms were genotyped for 471 RA patients and 684 healthy individuals. Correlation analysis was performed with clinical parameters, cardiovascular disease (CVD) and anti-citrullinated peptide/protein antibody (ACPA) presence. The sFLT-1 serum levels were evaluated., Results: The FLT-1 gene polymorphisms showed no significant differences in the proportion of cases and controls. Furthermore, the FLT-1 rs2296188 T/C polymorphism was associated with ACPA-positive RA. Overall, rs9943922 T/C and rs2296283 G/A are in almost completed linkage disequilibrium (LD) with D' = 0.97 and r2 = 0.83. The FLT-1 rs7324510 A allele has shown association with VAS score (p = 0.035), DAS-28 score (p = 0.013) and ExRA presence (p = 0.027). Moreover, other clinical parameters were also higher in RA patients with this allele. In addition, FLT-1 genetic variants conferred higher sFLT-1 levels in RA patients compared to controls., Conclusion: FLT-1 rs7324510 C/A variant may be a new genetic risk factor for severity of RA. Examined factor highly predispose to more severe disease activity as well as higher sFLT-1 levels in RA.

Objectives: Treat-to-target recommendations have identified 'remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE., Methods: An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%., Results: The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life., Conclusions: The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Rheumatoid arthritis (RA) is one of the autoimmune diseases, where different polymorphisms in cytokine genes play a pathogenic role. IL-12 is now recognized as a critical cytokine in terms of regulating the balance between Th1 and Th2 cells. We investigated the role of single nucleotide polymorphisms (SNPs) (rs3212227 (A/C) and rs17860508 (CTCTAA/GC)) of the IL-12B gene in the genetic susceptibility to RA and in the severity of the disease. Six hundred and thirty-four Caucasian RA patients and 341 healthy matched controls were studied using PCR-RFLP method and high-resolution melting analysis. Concentration of IL-12 cytokine level in serum was evaluated using ELISA. The genotype frequency did not deviate from HWE in each examined group. Frequencies of the rs3212227 CC genotype were statistically higher in patients with RA compared with the healthy control group in both codominant and recessive models (P = 0.037; P = 0.04, respectively). The frequency of rs3212227 C allele also showed similar tendency (P = 0.07). IL-12 level in serum was significantly higher in RA group compared with control (P < 0.0001). We observed that increased IL-12 serum level was correlated with higher number of tender and swollen joints, ExRA presence and higher levels of haemoglobin, CRP and PLT. Also higher IL-12 level in serum was observed within RA patients with hypertension. Present findings indicated that IL-12p40 + 1188A/C polymorphism as well as IL-12p70 protein levels may be associated with RA in the Polish population., (© 2016 The Foundation for the Scandinavian Journal of Immunology.)

Systemic lupus erythematosus (SLE) is a disease characterized by excessive proinflammatory cytokine production and damage to multiple organ systems. To investigate the potential association between cytokine gene polymorphisms and SLE, we performed a case-control study based on Polish population. SLE patients and controls, were examined for IL-23A rs11171806 G/A and IL-23R (rs1884444 G/T, rs10489629 G/A) by TaqMan SNP genotyping assay, for IL-17F rs763780 A/G and rs2397084A/G using the PCR- RFLP method. An increased frequency of AG genotype as well as G allele of the IL-17F rs763780 was found in patients with SLE, as compared with healthy subjects (OR = 3.947; p = 0.001 and OR = 3.538; p = 0.002, respectively). Frequencies of the rs1884444 TT genotype (OR = 138.1) and the rs1884444 T allele (OR = 2.176) were also higher in SLE patients (both p < 0.0001). Overall, weak LD was observed between the IL-17F rs763780 A/G and rs2397084 A/G polymorphisms (D'-0.003, r 2 - 0.000). From four possible haplotypes, frequencies of AG showed differences between both examined groups (p < 0.0001). We also observed a weak LD between the IL-23R rs10489629G/A and rs1884444 G/T (D'-0.199, r 2 -0.026). The genotype-phenotype analysis showed significant association between the IL-17F rs2397084 and mean value of the hemoglobin (p = 0.01), the IL-17F rs763780 and age (p = 0.008) and lupus anticoagulant (p = 0.09), the IL-23 rs11171806 and urea (p = 0.08) and C3 complement (p = 0.03), and the IL-23R rs1884444 G/T and activated partial thromboplastin time (p = 0.06). Present findings indicated that IL-17F rs763780 A/G and IL-23R rs1884444 G/T polymorphisms may be involved in susceptibility to SLE in the Polish population.

Background: Rheumatoid arthritis (RA) is one of the chronic autoimmune diseases, with genetic and environmental predisposition, and synovial angiogenesis is considered to be a notable stage in its pathogenesis. Angiogenesis or vascular proliferation has been suggested to be a pivotal mechanism involved in both inflammation/immune activation and joint invasion and destruction. RA may be considered an "angiogenic disease" because it is associated with active tissue neovascularization. Vascular endothelial growth factor (VEGF) promotes vascular permeability, regulates angiogenesis, endothelial cell proliferation and migration, chemotaxis, and capillary hyper permeability and therefore is involved in the development of inflammation. VEGF is the most potent proangiogenic molecule promoting the angiogenic phenotype of RA and is upregulated in RA., Objectives: The aim of the study was to identify functional VEGF variants and their possible association with VEGF expression, susceptibility to and severity of RA., Methods: 581 RA patients and of 341 healthy individuals were examined for -1154 A/G, -2578 A/C VEGF gene polymorphisms by PCR-RFLP method and for -634 G/C VEGF gene polymorphisms by TaqMan SNP genotyping assay. Serum VEGF levels in RA patients and controls were measured by ELISA., Results: The -1154 A/G VEGF gene polymorphism under the codominant, recessive (AA+AG vs. GG) and dominant (AA vs. AG+GG) models were associated with RA (p = 0.0009; p = 0.004; p = 0.017, respectively). VEGF -2578 A/C revealed differences in the case-control distribution in codominant, recessive, dominant and overdominant models (all p<0.0001). Furthermore, the -634 G/C VEGF gene SNP was not correlated with susceptibility to RA in Polish population. The genotype-phenotype analysis showed significant association between the VEGF -1154 A/G and -634 G/C and mean value of the hemoglobin (all p = 0.05), additionally they relevated that the number of women with the polymorphic allele -2578 C was lower than the number of women with wild type allele -2578A (p = 0.006). Serum VEGF levels were significantly higher in RA patients than in control groups (both p = 0,0001)., Conclusion: Present findings indicated that VEGF genetic polymorphism as well as VEGF protein levels may be associated with the susceptibility to RA in the Polish population.

To investigate the potential association between IL-12B and IL-27 gene polymorphisms and systemic lupus erythematosus (SLE), we performed a case-control study based on the Polish population. Patients with SLE and healthy individuals were examined for -6415 CTCTAA/GC (rs17860508) and +1188A/C (rs3212227) in IL-12B and -924A/G (rs153109) and 4730T/C (rs181206) in IL-27 gene polymorphisms using the high-resolution melting method, PCR-RFLP method and TaqMan SNP genotyping assay, respectively. An increased frequency of GC/GC genotype as well as GC allele of the IL-12B rs17860508 was found in patients with SLE, as compared with healthy subjects (P < 0.001). We did not find differences in genotype and allele frequencies of the IL-12B rs3212227 and IL-27 rs153109 and rs181206 variants between patients with SLE and controls. IL-27 haplotype rs181206C/rs153109G indicated higher risk for SLE (P = 0.002), whereas haplotype rs181206T/rs153109G indicated reduced risk for SLE (P = 0.005). The IL-12B rs3212227 A/C polymorphism was associated with the mean value of the platelets (PLT), urea and complement C3 level. Furthermore, IL-12B rs17860508 genetic variant showed correlation with PLT, prothrombin time, international normalized ratio and alkaline phosphatase. Our results revealed that IL-12B rs17860508 and IL-27 haplotype CG are genetic risk factors for SLE and that both IL-12B rs17860508 and rs3212227 predict disease phenotype., (© 2016 The Foundation for the Scandinavian Journal of Immunology.)

Background: In the present study, we aimed to evaluate whether polymorphisms within the RORc2 gene are involved in the risk and severity of rheumatoid arthritis (RA)., Methods: 591 RA patients and 341 healthy individuals were examined for RORc2 gene polymorphisms. Serum retinoic acid receptor-related orphan receptor C (RORc) levels were measured by enzyme-linked immunosorbent assay (ELISA)., Results: The rs9826 A/G, rs12045886 T/C and rs9017 G/A RORc2 gene SNPs show no significant differences in the proportion of cases and control. Overall, rs9826 and rs9017 were in high linkage disequilibrium (LD) with D' = 0.952 and r² = 0.874, except rs9826 and rs12045886; and rs12045886 and rs9017 in weak LD. The genotype-phenotype analysis showed a significant association between RORc2 rs9826 A/G and rs9017 G/A single nucleotide polymorphisms (SNPs) and median of C-reactive protein (CRP). Serum RORc levels was higher in RA patients with rs9826AA, rs12045886TT and -TC, and rs9017AA genotypes compared to healthy subjects with the same genotypes (p = 0.02, p = 0.04 and p = 0.01, respectively). Moreover, the median of RORc protein level was higher in RA patients with number of swollen joints bigger then 3 (p = 0.04) and with Health Assessment Questionnaires (HAQ) score bigger then 1.5 (0.049)., Conclusions: Current findings indicated that the RORc2 genetic polymorphism and the RORc2 protein level may be associated with severity of RA in the Polish population.

Objectives: Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disease with a prevalence of about 10 cases/100,000. It seems that in the pathogenesis of MCTD no individual cytokines/cells, but rather an altered pattern of these markers altogether may contribute to the autoimmune processes and their balance determines disease activity. IL-10, IL-12 and IL-17F as inflammatory cytokines might be an important functional candidate genes for autoimmune diseases including MCTD., Methods: The study group consisted of 66 patients with MCTD and of 106 (163 for IL-12B) healthy individuals. SNPs in the IL-10 (- 592C/A, - 1082G/A), IL-12B (+ 1188A/C) and IL-17F (His161Arg, Glu126Gly) genes were investigated by PCR-RFLP approach., Results: The frequency of the IL-10-592A and -1082A allele was higher in MCTD patients than in control groups (both p = 0,0000). In addition the -1082G/A IL-10 gene polymorphism was associated with esophageal involvement and with anti-U1-A and -C antibodies. The IL-17 7488A/G variant showed correlation with presence of anti-SmB and anti-dsDNA antibodies, while the IL-17F 7383A/G variant was associated with Sjögren's syndrome and leuco-and thrombocytopenia. Moreover, the IL-12 SNP + 1188A/C showed correlation with sclerodactyly in MCTD patients., Conclusion: Present findings indicate that IL-10 gene variants may be considered as genetic risk factors for MCTD susceptibility.

One among many factors involved in induction of rheumatoid arthritis (RA) are T cells, the differentiation of which depends upon a unique combination of stimulants and subsequent activation of diverse transcription factors. The aim of this study was to identify polymorphic variants in Smad3 and NFATc2 genes and their possible association with susceptibility to and severity of RA. A total of 272 RA patients, 321 for Smad3 and 304 for nuclear factor of activated T cells (NFAT)c2 healthy individuals, were examined for rs6494629 C/T and rs2289263 T/G Smad3 and rs880324 NFATc2 gene polymorphisms using the polymerase chain reaction-fragment length polymorphism (PCR-RFLP) method and TaqMan single nucleotide polymorphism (SNP) genotyping assay, respectively. Serum Smad3 and NFATc2 levels in RA patients and controls were measured by enzyme-linked immunosorbent assay (ELISA). The rs6494629 C/T Smad3 gene polymorphism under the recessive (TT versus CC+CT) and over-dominant (CC+TT versus CT) models were associated with RA (P=0.014 and P=0.008, respectively). Smad3 rs2289263 T/G revealed differences in the case-control distribution in co-dominant, recessive and over-dominant models (P=0.037, P=0.010, P=0.034). Overall, rs6494629 C/T and rs2289263 T/G Smad3 gene polymorphisms were in a weak linkage disequilibrium (LD) with D'=0.116 and r(2)=0.004. After Bonferroni correction, the genotype-phenotype analysis showed no significant correlation of the Smad3 rs6494629 C/T and rs2289263 T/G and NFATc2 rs2289263 TT polymorphisms with disease activity, joint damage and extra-articular manifestation in RA patients. Serum Smad3 and NFATc2 levels were significantly higher in RA patients than in control groups (both P=0 0000). The present findings indicated that Smad3 genetic polymorphisms may be associated with the susceptibility to RA in the Polish population., (© 2014 British Society for Immunology.)

Objective: The aim of the study was to identify 2 polymorphic variants in the promoter region of the Foxp3 gene and their possible association with susceptibility to and severity of rheumatoid arthritis (RA). The association between genetic factors and pathogenesis suggests that T cells take part in the induction of RA. The CD4+CD25highFoxp3+ subset of regulatory T cells plays an essential role in preventing autoimmunity and maintaining immune homeostasis., Methods: Patients with RA (n = 274) and healthy individuals (n = 295) were examined for -3279 C/A and -924 A/G Foxp3 gene polymorphisms by the polymerase chain reaction-restriction fragment-length polymorphism method. Serum Foxp3 levels in patients with RA and controls were measured with ELISA., Results: Foxp3 -3279 A and -924 G alleles were associated with significantly elevated risk of RA in the population tested (p = 0.003 and p = 0.004, respectively) compared to the wild-type alleles. Overall, -3279 C/A and -924 A/G Foxp3 gene polymorphisms were in indistinct linkage disequilibrium with D' = 0.481 and r(2) = 0.225. From 4 possible haplotypes, frequencies of 2 (AG and CA) showed significant differences between both examined groups (respectively, p < 0.001 and p = 0.007). After appropriate adjustment of Bonferroni correction for multiple testing, the genotype-phenotype analysis showed no significant correlation of the Foxp3 -3279 C/A and -924 A/G polymorphisms with the disease activity, joint damage, laboratory variables, and extraarticular manifestation in patients with RA. Serum Foxp3 level was significantly higher in patients than in controls (p < 0.0001)., Conclusion: Current findings indicated that the Foxp3 genetic polymorphism and the Foxp3 protein level may be associated with susceptibility to RA in the Polish population.

Rheumatoid arthritis (RA) is one of the autoimmune diseases, where different polymorphisms in cytokine genes play a pathogenic role. Interleukin 27 (IL-27) is a novel pro-/anti-inflammatory cytokine, an excellent candidate for chronic inflammatory disease studies. The aim of the study was to identify polymorphisms in the IL-27 gene and their possible association with susceptibility to and severity of RA. Two hundred and seventy-four patients with RA and of 295 healthy individuals were examined for -924A/G and 4730T/C IL27 gene polymorphisms using PCR-RFLP method and TaqMan SNP genotyping assay, respectively. Haplotype frequencies of IL-27 polymorphisms were estimated using SHEsis platform. Frequencies of the -924GG genotype and the -924G allele were statistically higher in RA patients comparing with the healthy control group (P = 0.008 and P = 0.004, respectively). Overall, strong LD was observed between the IL27 gene -924A/G and 4730 T/C polymorphisms (D' = 0.613, r2 = 0.199). From four possible haplotypes, frequencies of two (CA and CG) showed significant differences between both examined groups (respectively: P < 0.001 and P = 0.001062). The genotype-phenotype analysis showed significant association between the IL-27 4730 T/C polymorphism and HAQ score and means value of the ESR, additionally they revealed that individuals with the polymorphic allele -924G had more advanced disease than wild-type allele carriers. Present findings indicated that IL27 -924A/G polymorphism may be involved in susceptibility to RA in the Polish population., (© 2014 John Wiley & Sons Ltd.)

Objective: To investigate the impact of iron status on survival in patients with type 2 diabetes and coronary artery disease (CAD)., Research Design and Methods: Serum ferritin, transferrin saturation (Tsat), and soluble transferrin receptor (sTfR) were measured in 287 patients with type 2 diabetes and stable CAD (65 ± 9 years of age, 78% men)., Results: During a mean follow-up of 45 ± 19 months, there were 59 (21%) deaths and 60 (21%) cardiovascular hospitalizations. Both serum ferritin and sTfR strongly predicted 5-year all-cause mortality rates, independently of other variables (including hemoglobin, measures of renal function, inflammation, and neurohormonal activation). There was an exponential relationship between sTfR and mortality (adjusted hazard ratio [HR] per 1 log mg/L: 4.24 [95% CI 1.43-12.58], P = 0.01), whereas the relationship between ferritin and mortality was U-shaped (for the lowest and the highest quintiles vs. the middle quintile [reference group], respectively: adjusted HR 7.18 [95% CI 2.03-25.46], P = 0.002, and adjusted HR 5.12 [1.48-17.73], P = 0.01). Similar patterns were observed for the composite outcome of all-cause mortality or cardiovascular hospitalization, and in these multivariable models, low Tsat was related to unfavorable outcome., Conclusions: Both low and high serum ferritin (possibly reflecting depleted and excessive iron stores, respectively) along with high serum sTfR (reflecting reduced metabolically available iron) identify patients with type 2 diabetes and CAD who have a poor prognosis.

There is one study on the association of the CD40 G > T (rs4810485) single nucleotide polymorphism (SNP) as a risk factor of systemic lupus erythematosus (SLE). Therefore, we studied the prevalence of the CD40 G > T SNP in patients with SLE (n = 261) and controls (n = 545) in a Polish population. We did not find significant differences between the CD40 G > T genotype and allele frequency in patients with SLE and healthy individuals. However, the frequency of the CD40 TT and GT genotypes was statistically different between patients with arthritis and neurologic manifestations and patients without these symptoms (OR = 0.2009 (95% CI = 0.07547-0.5348, p = 0.0004, p (corr) = 0.0068) and OR = 0.2876 (95% CI = 0.1371-0.6031, p = 0.0005, p (corr) = 0.0085) respectively). Our observations indicate that the CD40 T variant might be negatively associated with some clinical disease manifestations in patients with SLE.

Objective: The aims of the study were to assess cognitive functions (CF) in patients with mixed connective tissue disease (MCTD) and to compare MCTD patients with systemic lupus erythematosus patients with and without neuropsychiatric manifestations (NP-SLE and non-NP-SLE, respectively) in terms of CF., Methods: Neuropsychological examination was performed in 141 patients: 30 with MCTD (24 women, 6 men), mean age: 48.07 years, 37 with non-NP-SLE (36 women, 1 man), mean age: 40.76 years and 74 with NP-SLE (68 women, 6 men), mean age: 41.97 years. Neuropsychological tests and structured interview were used. Emotional state was assessed by Hospital Anxiety and Depression Scale and clinical review., Results: We observed cognitive impairment in six MCTD patients (20%); in one (3%) the impairment was severe. MCTD patients achieved significantly higher results in seven out of 11 tests compared with patients with NP-SLE. MCTD and non-NP-SLE patients did not differ significantly. The differences were irrespective of premorbid IQ, education, disease duration and steroid treatment., Conclusions: In the majority of MCTD patients, CF were not impaired and severe impairment was unusual. Cognitive functioning was most disturbed in NP-SLE. The cognitive deficits observed in connective tissue diseases can be connected with nervous system involvement.

Cytokines are implied in polymyositis/dermatomyositis (PM/DM) pathogenesis. Our aim was to evaluate the serum levels of interleukin-15 (IL-15), soluble receptors for IL-2 (sIL-2R) and TNF-alpha type 1 receptor (sTNF-R1) in PM/DM patients and their relation to disease activity and clinical symptoms. Thirty-eight patients who met definite or probable criteria of Bohan and Peter for DM/PM were included into the study. Results in patients with active (41 observations) and inactive disease (24 observations) were compared with control (15 subjects). The median level of IL-15 was 47.6 ± 170 pg/ml in active patients, 25.15 ± 240 pg/ml in inactive and 28.5 ± 28.89 pg/ml in controls. We demonstrated significant differences between active patients and controls in levels of IL-15 (0.016, 95%CI 1.39-57.1). The median level of sIL-2R was 314 ± 388, 235.3 ± 269 and 144.3 ± 152.9 pg/ml, and the median level of sTNF-R1 was 350 ± 388; 294.7 ± 204.7; 209.5 ± 105.9 pg/ml in active, inactive and control subjects, respectively. There were significantly higher serum levels of these cytokines in active patients than in control subjects (for sIL-2R P = 0.05, CI95% 0.4-331; and sTNF-R1 P = 0.031, CI95% 15.1-321.5). The interleukin levels did not differ between inactive patients and controls. Elevation of IL-15, sIL2-R and sTNF-R1 in active patients provides preliminary evidence for the activation of inflammatory response during PM/DM flares. Further studies may be needed to explain the mechanisms driving these diseases.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology, and the limited available therapeutic options for this disease, are frustrating to both clinicians and patients. However, recent advances in the understanding of disease mechanisms have given rise to numerous studies on specific approaches to SLE treatment. Rituximab, the first chimeric, mouse-human monoclonal antibody which is directed against CD20, seems to be a new therapeutic option. The purpose of this review is to explain the current clinical evidence on the therapeutic use of rituximab in adult SLE patients. Two randomized clinical trials with rituximab (the EXPLORER and LUNAR studies) failed to prove efficacy of this drug on SLE. Ongoing data analysis continues to explain the reasons behind why this treatment fails to work. However data from open source and observational studies contrast with clinical trials results. The global analysis of this data supports the off-label use of rituximab in subsets of SLE that are refractory to standard treatment.

Oestrogens acting via nuclear receptors (encoded by ESR1 or ESR2) are important for pathogenesis of systemic lupus erythematosus (SLE). rs2234693 and rs4986938 are two single nucleotide polymorphisms (SNPs) whose C and A variants increase transcription of ESR1 and ESR2, respectively. The T allele of rs2234693 was associated with early onset SLE, whereas the role of rs4986938 in SLE was not reported. Our aim was to examine the role of rs2234693 and rs4986938 in conferring susceptibility to juvenile and adult SLE (jSLE and aSLE). Genotype distribution of both SNPs was analysed in 84 jSLE, 112 aSLE patients and 1001 controls. Allele C of rs2234693 was associated with jSLE (OR = 1.87, p = 0.006, p(corrected) = 0.02), whereas allele A of rs4986938 showed an association with aSLE (OR = 1.46, p = 0.008, p(corrected) = 0.03). In jSLE, rs2234693 C had lower frequency in patients with central nervous system involvement (OR = 0.39, p = 0.005, p(corrected) = 0.04) and showed a trend for increase among males, patients with renal involvement and those without DR2/3 (p < 0.05, p(corrected) > 0.05). Whereas our results are consistent with a role of ESR1 variation in jSLE, more studies are needed since the direction of association was the opposite of that reported previously. The association between rs4986938 (ESR2) and aSLE is a novel finding, consistent with our recent report associating this variant with Graves' disease.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology and limited available therapeutic options frustrating both clinicians and patients. However, recent advances in the understanding of disease mechanisms have given rise to numerous studies on specific approaches to SLE treatment. The purpose of this review is to explain the rationale for new treatments and results of the first clinical studies. We will focus on agents which deplete B cells (anti-CD20, anti-CD22), block cytokines (TNF α, Il 6), inhibit B/T cells interaction (CTLA-4Ig, anti-CD40L), or are even expected to reconstruct physiologic immunotolerance. Although preliminary results seemed promising, two randomized clinical trials with rituximab (EXPLORER and LUNAR study) failed to prove efficacy. Data analysis continues to explain the reasons. Trial design, subject population, limitations of the outcome measure instrument and site qualification have been questioned. Future studies are likely to focus on specific organ involvement or treatment combinations with other immunosuppressive agents.

An inception cohort of patients with systemic lupus erythematosus from 14 European centres was followed for up to 5 years in order to describe the current early disease course. At inclusion patients (n = 200, 89% female, mean age 35 years, 97% Caucasian, mean SLEDAI 12.2) fulfilled a mean of 6.5 ACR classification criteria. The most prevalent criteria were antinuclear Ab presence (97%) followed by anti-dsDNA Ab (74%), arthritis (69%), leukocytopenia (54%) and malar rash (53%), antiphospholipid Ab (48%) and anti-synovial membrane Ab (21.6%). Clinical signs of lupus nephritis (LN) were present in 39% with biopsy-confirmed LN seen in 25%. Frequent additional findings were hypocomplementaemia (54%), anti-SSA Ab (49%), alopecia (26%) and Raynaud's phenomenon (31%). There were few regional differences in disease presentation and management. One and 5-year survival rates were 99% and 97% respectively. During the mean follow-up of 4.1 years 25% entered a state of early disease quiescence by global physician assessment, but the overall risk of subsequent flare was 60%. Maximum SLEDAI scores decreased over time, but 45% of patients accrued damage (SDI >or=1) for which baseline presence of proteinuria and persistent disease activity were independent predictors. The results indicate minor differences in SLE presentation and treatment within various regions of Europe and a high diagnostic reliance on anti-dsDNA Ab. Despite early reductions in disease activity and improved mortality, the risk for disease flare and damage development is, however, still substantial, especially in patients not entering an early remission.

Current therapeutic and diagnostic resources have turned systemic lupus erythematosus (SLE) into a chronic disease by reducing mortality rates. The exact contribution of disease activity and disease related damage to mortality is not well studied. The aim of this study was to describe the current causes of death (COD) in a multinational European cohort of patients with SLE in relation to quantified measures of disease activity and damage. Prospective five-year observational study of case fatalities in SLE patients at 12 European centres was performed. Demographics, disease manifestations, interventions and quantified disease activity (by ECLAM and SLEDAI) and damage (by SLICC-DI) at the time of death were related to the various COD. Ninety-one case fatalities (89% females) occurred after median disease duration of 10.2 years (range 0.2-40) corresponding to a annual case fatality of one for each of the participating cohorts. Cumulative mortality correlated linearly with disease duration with nearly 10% of fatalities occurring in the first year and 40% after more than 10 years of disease. Death occurred during SLE remission in one third of cases. In the remaining cases a mixture of disease activity (median ECLAM 5.5, median SLEDAI 15) and accrued damage (median SLICC-DI 5.0) with opposing relationships to disease duration contributed to death. Infections and cardiovascular events were the most frequent COD in both early and late fatalities with no gender differences for type of COD, disease activity, damage or comorbidity. In Europe, case fatalities have become uncommon events in dedicated SLE cohorts. The bimodal mortality curve has flattened out and deaths now occur evenly throughout the disease course with infectious and cardiovascular complications as the main direct COD in both early and late fatalities. Accrued damage supplants disease activity over time as the main SLE specific contributor to death over time.

The idiopathic inflammatory myopathies are a heterogeneous group of diseases that can involve various systems. Antibodies directed against aminoacyl-tRNA synthetases, such as anti-Jo-1 antibodies, are strongly associated with a syndrome which consists of myositis, interstitial lung disease (ILD), arthritis and Raynaud's phenomenon. Forty-one patients with various forms of idiopathic inflammatory myopathies were assessed: 14 patients with anti-Jo-1 antibodies and 27 patients without anti-Jo-1 antibodies as a control group. We retrospectively analysed clinical symptoms, treatment and outcome in both groups. Patients with anti-Jo-1 antibodies more often had ILD (64.2 vs. 11.1%), arthritis (64.2 vs. 18.1%) and Raynaud's phenomenon (38 vs. 0%). Patients without the anti-Jo-1 antibody presented worse muscle strength and more frequently myalgia (37 vs. 21%), cutaneous rash (18.5 vs. 7%), heliotrope rash (29% vs. 7%) and periungueal changes (22 vs. 0%) than the anti-Jo-1-positive patients. Outcome was good in both groups. Improvement was achieved in the 14 (100%) Jo-1 positive patients, and in 25 (92.5%) controls. Two (7.5%) patients from control group achieved remission.