Myositis-related autoantibody profile and clinical characteristics stratified by anti-cytosolic 5'-nucleotidase 1A status in connective tissue diseases.

Introduction/aims: Cytosolic 5'-nucleotidase 1A (cN-1A) autoantibodies have been recognized as myositis-related autoantibodies. However, their correlations with clinical characteristics and other myositis-specific and myositis-associated autoantibodies (MSAs/MAAs) are still unclear. We aimed to establish the prevalence and clinical and laboratory associations of cN-1A autoantibodies in a cohort of patients with connective tissue diseases.

Elevated Antibody Titers to Epstein-Barr Virus and Cytomegalovirus in Patients with Drug-Induced Lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease, which has been associated with Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection. Drug-induced lupus (DIL) is a lupus-like disease caused by the intake of therapeutic drugs, which has been estimated to cause approximately 10-15% of lupus-like cases. Although SLE and DIL share common clinical symptoms, there are some fundamental differences between DIL and SLE onset.

A cluster of type II interferon-regulated genes associates with disease activity in patients with systemic lupus erythematosus.

Upregulation of interferon-regulated genes (IRGs), denoted IFN signature, in peripheral blood has been used as an indirect measure of IFN pathway activation in patients with systemic lupus erythematosus (SLE). However, it has not been determined, which IFN signatures that optimally reflect clinical disease activity. In this study, we determined an IFN signature based on the expression of 128 IRGs in whole blood from 34 SLE patients in a cross-sectional (CS) study, 11 with active lupus nephritis followed longitudinally (LS) and 15 healthy controls.

Galectin-3-binding protein is a novel predictor of venous thromboembolism in systemic lupus erythematosus.

Objectives: Venous (VTE) and arterial (AT) thrombosis in systemic lupus erythematosus (SLE) are poorly explained and difficult to predict. Leptin and tumour necrosis factor-like weak inducer of apoptosis (TWEAK) have been linked to subclinical atherosclerosis and galectin-3-binding protein (G3BP) to type I interferon activation and a pro-thrombotic environment. Thus, we explore serum G3BP, interferon gamma-induced protein 10 (IP-10), soluble CD163 (sCD163), TWEAK and leptin as predictors of VTE and AT, damage accrual, and all-cause mortality during follow-up in a Swedish SLE cohort.

Stimulation of Mononuclear Cells Through Toll-Like Receptor 9 Induces Release of Microvesicles Expressing Double-Stranded DNA and Galectin 3-Binding Protein in an Interferon-α-Dependent Manner.

Microvesicles (MVs) expressing the type 1 interferon (IFN)-inducible protein galectin-3 binding protein (G3BP) may play a pathogenic role in systemic lupus erythematosus (SLE). Co-expression of double-stranded DNA (dsDNA) on such MVs may render them immunogenic and targets for anti-dsDNA antibodies. Little is known about the mechanisms underlying generation of this MV population.

Clinical and Serological Associations with the Development of Incident Proteinuria in Danish Patients with Systemic Lupus Erythematosus.

Objective: In a longitudinal cohort study, we investigated whether clinical and serological manifestations at the time of classification of systemic lupus erythematosus (SLE) were predictive of subsequent development of incident proteinuria as a biomarker of incident lupus nephritis.

Methods: Patients fulfilling SLE classification criteria but having no proteinuria prior to or at the time of classification were included. Data on SLE manifestations, vital status, criteria-related autoantibodies, and SLE-associated medications were collected during clinical visits and supplemented by chart review.

Antibodies to a strain-specific citrullinated Epstein-Barr virus peptide diagnoses rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Anti-citrullinated protein antibodies (ACPA) are crucial for the serological diagnosis of RA, where Epstein-Barr virus (EBV) has been suggested to be an environmental agent in triggering the onset of the disease. This study aimed to analyse antibody reactivity to citrullinated EBV nuclear antigen-2 (EBNA-2) peptides from three different EBV strains (B95-8, GD1 and AG876) using streptavidin capture enzyme-linked immunosorbent assay.

The use of synthetic peptides for detection of anti-citrullinated protein antibodies in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. A characteristic feature of RA is the presence of anti-citrullinated protein antibodies (ACPA). Since ACPAs are highly specific for RA and are often present before the onset of RA symptoms, they have become valuable diagnostic and prognostic.

Endothelial dysfunction is associated with activation of the type I interferon system and platelets in patients with systemic lupus erythematosus.

Objectives: Endothelial dysfunction may be connected to cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). Type I interferons (IFNs) are central in SLE pathogenesis and are suggested to induce both endothelial dysfunction and platelet activation. In this study, we investigated the interplay between endothelial dysfunction, platelets and type I IFN in SLE.

Distinct proteome pathology of circulating microparticles in systemic lupus erythematosus.

Background: The pathogenesis of systemic lupus erythematosus (SLE) is poorly understood but has been linked to defective clearance of subcellular particulate material from the circulation. This study investigates the origin, formation, and specificity of circulating microparticles (MPs) in patients with SLE based on comprehensive MP proteome profiling using patients with systemic sclerosis (SSc) and healthy donors (HC) as controls.

Methods: We purified MPs from platelet-poor plasma using differential centrifugation of samples from SLE (n = 45), SSc (n = 38), and two sets of HC (n = 35, n = 25).

Complexes of DNA with fluorescent dyes are effective reagents for detection of autoimmune antibodies.

To date, there are multiple assays developed that detect and quantify antibodies in biofluids. Nevertheless, there is still a lack of simple approaches that specifically detect autoimmune antibodies to double-stranded DNA. Herein we investigate the potential of novel nucleic acid complexes as targets for these antibodies.

Synthetic oligonucleotide antigens modified with locked nucleic acids detect disease specific antibodies.

New techniques to detect and quantify antibodies to nucleic acids would provide a significant advance over current methods, which often lack specificity. We investigate the potential of novel antigens containing locked nucleic acids (LNAs) as targets for antibodies. Particularly, employing molecular dynamics we predict optimal nucleotide composition for targeting DNA-binding antibodies.

Application of synthetic peptides for detection of anti-citrullinated peptide antibodies.

Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and represent an important tool for the serological diagnosis of RA. In this study, we describe ACPA reactivity to overlapping citrullinated Epstein-Barr virus nuclear antigen-1 (EBNA-1)-derived peptides and analyze their potential as substrates for ACPA detection by streptavidin capture enzyme-linked immunosorbent assay. Using systematically overlapping peptides, containing a 10 amino acid overlap, labelled with biotin C-terminally or N-terminally, sera from 160 individuals (RA sera (n=60), healthy controls (n=40), systemic lupus erythematosus (n=20), Sjögren's syndrome (n=40)) were screened for antibody reactivity.

Elevated platelet expression of CD36 may contribute to increased risk of thrombo-embolism in active inflammatory bowel disease.

Context: Inflammatory bowel disease (IBD) induces increased risk of thrombo-embolism. CD36 is involved in platelet activation, glucose metabolism and inflammation.

Objective: The relationship between CD36 expression on platelets and monocytes, plasma sCD36, and CD36-positive platelet-derived microparticles (PDMPs) and inflammation in both active IBD and after one week of anti-tumour necrosis alpha antibody (anti-TNF) treatment was investigated.

Detection of antibodies to the 20s proteasome by ELISA.

The presence of antibodies against the 20S proteasome has been correlated with diseases like multiple sclerosis (MS) and systemic lupus erythematosus (SLE) but no definite association has been established. In order to investigate this further, we optimized an ELISA for proteasome antibodies and applied it to test a total of 324 serum and plasma samples from MS patients, SLE patients, and healthy controls. Our results yield a functional and reliable assay but no correlation between the amount of proteasome antibodies present and the development of MS or SLE could be established.

Circulating microparticles in systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease presenting with a wide array of clinical manifestations and an elusive pathogenesis. A characteristic feature in SLE is the occurrence of autoantibodies against chromatin, double-stranded DNA, and RNA-binding ribonucleoproteins. Observations of defective clearance of dying cells in SLE combined with the generation and exposure of nuclear autoantigens during apoptosis have led to the hypothesis that improperly cleared apoptotic debris constitutes a source of autoantigens capable of triggering autoimmune disease.