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1.
Scand J Rheumatol ; : 1-10, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38913821

ABSTRACT

OBJECTIVE: Autoantibodies directed against the intracellular protein bicaudal D2 (BICD2) have been identified as a specific marker of systemic sclerosis (SSc). Since autoantibodies are of value in predicting disease onset and identifying meaningful clinical subsets, as well as having prognostic value, this study aimed to establish the prevalence of BICD2 autoantibodies (anti-BICD2) in a cohort of patients with connective tissue disease and healthy controls. METHOD: In this cross-sectional study, 363 patients with connective tissue disease (121 SSc, 141 systemic lupus erythematosus, 101 myositis, and 100 blood donors) were tested for the presence of anti-BICD2. All SSc patients were tested for specific anti-nuclear antibodies (ANAs), and clinical and laboratory associations were evaluated in the SSc patients, stratified by anti-BICD2 status. RESULTS: In the SSc cohort, 35 patients had autoantibodies directed against BICD2. The specificity of anti-BICD2 in SSc patients was 96.5%; however, the sensitivity was only 28.9%. Anti-BICD2 and centromere autoantibodies were present together in 91% of the anti-BICD2-positive SSc patients, and in none of the cases was anti-BICD2 the only antibody present. Anti-BICD2-positive patients had lower forced expiratory volume in 1 s (FEV1) (p = 0.01) and lower carbon monoxide transfer coefficient (KCO) (p = 0.01) than anti-BICD2-negative SSc patients, but they had higher forced vital capacity (p = 0.03). CONCLUSION: Autoantibodies against BICD2 were highly specific for SSc patients. Reduced FEV1 and KCO in anti-BICD2-positive patients may indicate that the presence of anti-BICD2 is associated with altered lung function in an unknown pathophysiological manner, which awaits further elucidation.

2.
Scand J Rheumatol ; 42(6): 473-82, 2013.
Article in English | MEDLINE | ID: mdl-24016306

ABSTRACT

OBJECTIVES: Microparticles (MPs) may be involved in the pathogenesis of systemic sclerosis (SSc), which includes vasculopathy, endothelial cell activation, and coagulation activation. Circulating MPs from SSc patients were characterized and their relationship with soluble markers of vascular activation investigated. METHOD: This study included 121 SSc patients [79 with limited (lcSSc) and 42 with diffuse cutaneous SSc (dcSSc)] and 49 sex- and age-matched healthy controls (HCs). The MPs were characterized by flow cytometry for annexin V (AnxV)-binding capacity and their expression of surface markers of platelets (PMPs), leucocytes (LMPs), or endothelial cells (EMPs). Plasma levels of soluble (s) E- and P-selectins were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The total concentrations of MPs and of PMPs, LMPs, and EMPs were 22-42% lower in SSc patients than in HCs (p < 0.001). However, within the cell-derived MP pool, a 47% higher fraction of AnxV non-binding MPs (F-AnxV(-) MPs) was found in the SSc patients compared to the HCs (p < 0.05). The plasma levels of sE- and sP-selectins were increased by 47-64% in the SSc patients compared to HCs (p < 0.001). Multiple regression analysis showed that the raised plasma levels of sE- and sP-selectin were associated with F-AnxV(-) EMPs in dcSSc patients (p = 0.008 and p = 0.001, respectively) but not in lcSSc patients (p = 0.33 and p = 0.82, respectively). CONCLUSIONS: While the total number of MPs was decreased, the number of F-AnxV(-) MPs increased in SSc patients. The F-AnxV(-) EMPs were associated with plasma levels of markers of vascular activation in patients with dcSSc.


Subject(s)
Cell-Derived Microparticles/pathology , E-Selectin/blood , P-Selectin/blood , Scleroderma, Systemic/blood , Scleroderma, Systemic/pathology , Adult , Aged , Annexin A5/metabolism , Biomarkers/blood , Blood Platelets/pathology , Case-Control Studies , Cell Count , Cross-Sectional Studies , Endothelium, Vascular/pathology , Female , Humans , Leukocytes/pathology , Male , Middle Aged , Regression Analysis
3.
Scand J Rheumatol ; 41(4): 280-9, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22646970

ABSTRACT

OBJECTIVE: We sought to determine whether the serological response towards lytic cycle antigens of Epstein-Barr virus (EBV) is altered in systemic lupus erythematosus (SLE) patients. METHOD: We used enzyme-linked immunosorbent assay (ELISA) to investigate the prevalence of EBV early antigen diffuse (EBV-EA/D) antibodies in sera from 60 patients with SLE, 40 with scleroderma (SSc), 20 with primary Sjögren's syndrome (pSS), 20 with rheumatoid arthritis (RA), 20 healthy controls, and also subjects with various circulating autoantibodies. Samples from patients were obtained from clinics specialized within the diseases in Denmark and Sweden and samples from healthy controls were obtained from volunteers. RESULTS: A significant elevated titre of immunoglobulin (Ig)A, IgG, and IgM EBV-EA/D antibodies was found in SLE patients compared to healthy controls, a finding not explained by immunosuppressive treatment or disease activity. The largest difference was observed for IgA EBV-EA/D antibodies (p = 0.0013) with a seropositive rate of 58% in SLE patients and 0% in healthy controls. RA and SSc patients and individuals seropositive for anti-Scl-70 were additionally found to have elevated titres of IgA EBV-EA/D antibodies (40%, p = 0.014; 60%, p = 0.015; and 38.5%, p = 0.045, respectively). However, the titres were generally lower than in SLE patients. CONCLUSION: Our findings support an association between EBV and SLE. The elevated titre of EBV-EA/D-directed IgA antibodies found in SLE patients could suggest reactivation of EBV in epithelial cells or reinfection of epithelial cells after reactivation in B cells, indicating lack of control of the latent infection.


Subject(s)
Antigens, Viral/immunology , Immunoglobulin A/blood , Lupus Erythematosus, Systemic/immunology , Adult , Aged , Antigens, Viral/blood , Female , Humans , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/virology , Male , Middle Aged
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