Effects of childhood-onset systemic lupus erythematosus on academic achievements and employment in adult life

Objective. Long-term outcome data in adults with childhood-onset systemic lupus erythematosus (cSLE) are limited. Here, we report the effects of cSLE on education, vocation, and employment in a large cohort of adults with cSLE.Methods. Patients were seen for a single study visit comprising a structured history and physical examination. Medical records were retrieved to supplement information obtained during the study visit. Education and employment status were assessed by questionnaires. I Iealth-related quality of life (HRQOL) was measured with the 36-Item Short Form Health Survey (SF-36).Results. One hundred six patients with cSLE (93% female, 73% White), with a median disease duration of 20 years, completed the visit and questionnaires. Almost all patients stated that cSLE had influenced their education, but the level of completed education was similar to the general Dutch population. Half of the patients had adjusted their vocational choice due to the disease. Still, 44% of patients who had finished education did not have a paid job. Of the employed patients, 61% worked part time. Disease damage was equally prevalent in patients with and without paid employment. A high percentage of patients (51%) were declared work disabled, due to disease damage. Patients who did not have paid employment were often work disabled. Both had a negative effect on HRQOL.Conclusion. The effect of cSLE on academic achievements and employment is substantial, despite patients adjusting their educational and vocational choices. To optimize participation in the community, ongoing support is necessary, not only to help patients find suitable education and vocations but also to offer guidance regarding potential adjustments during their career.Nephrolog

Fc-gamma receptor polymorphisms differentially influence susceptibility to systemic lupus erythematosus and lupus nephritis

OBJECTIVE: To determine relevant Fc-gamma receptor (FcgammaR) polymorphisms in relation to susceptibility to SLE and LN, and to determine the functional consequences of genetic associations found. METHODS: Using multiplex ligation-dependent probe amplification, copy number regions (CNRs) and relevant known functional single nucleotide polymorphisms of FcgammaRII and FcgammaRIII were determined in a LN-enriched cohort of 266 Dutch Caucasian SLE patients and 919 healthy Caucasian controls. Expression of FcgammaRs on leukocytes was assessed using flow cytometry. RESULTS: In multivariable analysis, low copy number of CNR1 (includingFCGR3B; odds ratio (OR) 2.04; 95% CI: 1.29, 3.23),FCGR2A-131RR (OR 2.00; 95% CI: 1.33, 2.99), and the 2B.4 haplotype ofFCGR2B(OR 1.59; 95% CI: 1.13, 2.24), but notFCGR2Copen reading frame, were significantly (all P < 0.01) and independently associated with susceptibility to SLE. The 2B.4 haplotype was negatively associated with LN and led to surface expression of FcgammaRIIb on neutrophils and monocytes. CONCLUSION: This study is the first to investigate the most relevant and functional single nucleotide polymorphisms and copy number variations of FcgammaRII and FcgammaRIII polymorphisms in one study population, enabling the determination of the individual contribution of each polymorphism in multivariable analysis. Three polymorphisms were shown to be independently associated with susceptibility to SLE. The novel findings of a negative association of the 2B.4 haplotype with LN, and increased expression of FcgammaRIIb on neutrophils and monocytes as a result of this 2B.4 haplotype warrant future research in the role of these cells and FcgammaRs in the pathogenesis of SLE and LN

Autoantibody Specificities and Type I Interferon Pathway Activation in Idiopathic Inflammatory Myopathies

Myositis is a heterogeneous group of autoimmune diseases, with different pathogenic mechanisms contributing to the different subsets of disease. The aim of this study was to test whether the autoantibody profile in patients with myositis is associated with a type I interferon (IFN) signature, as in patients with systemic lupus erythematous (SLE). Patients with myositis were prospectively enrolled in the study and compared to healthy controls and to patients with SLE. Autoantibody status was analysed using an immunoassay system and immunoprecipitation. Type I IFN activity in whole blood was determined using direct gene expression analysis. Serum IFN-inducing activity was tested using peripheral blood cells from healthy donors. Blocking experiments were performed by neutralizing anti-IFNAR or anti-IFN-α antibodies. Patients were categorized into IFN high and IFN low based on an IFN score. Patients with autoantibodies against RNA-binding proteins had a higher IFN score compared to patients without these antibodies, and the IFN score was related to autoantibody multispecificity. Patients with dermatomyositis (DM) and inclusion body myositis (IBM) had a higher IFN score compared to the other subgroups. Serum type I IFN bioactivity was blocked by neutralizing anti-IFNAR or anti-IFN-α antibodies. To conclude, a high IFN score was not only associated with DM, as previously reported, and IBM, but also with autoantibody monospecificity against several RNA-binding proteins and with autoantibody multispecificity. These studies identify IFN-α in sera as a trigger for activation of the type I IFN pathway in peripheral blood and support IFN-α as a possible target for therapy in these patients. © 2016 The Foundation for the Scandinavian Journal of Immunolog