Circulating immune-complexes of IgG/IgM bound to B2-glycoprotein-I associated with complement consumption and thrombocytopenia in antiphospholipid syndrome.

Background: Antiphospholipid syndrome (APS) is a multisystemic autoimmune disorder characterized by thrombotic events and/or gestational morbidity in patients with antiphospholipid antibodies (aPL). In a previous single center study, APS-related clinical manifestations that were not included in the classification criteria (livedo reticularis, thrombocytopenia, leukopenia) were associated with the presence of circulating immune-complexes (CIC) formed by beta-2-glycoprotein-I (B2GP1) and anti-B2GP1 antibodies (B2-CIC). We have performed a multicenter study on APS features associated with the presence of B2-CIC. Methods: A multicenter, cross-sectional and observational study was conducted on 303 patients recruited from six European hospitals who fulfilled APS classification criteria: 165 patients had primary APS and 138 APS associated with other systemic autoimmune diseases (mainly systemic lupus erythematosus, N=112). Prevalence of B2-CIC (IgG/IgM isotypes) and its association with clinical manifestations and biomarkers related to the disease activity were evaluated. Results: B2-CIC prevalence in APS patients was 39.3%. B2-CIC-positive patients with thrombotic APS presented a higher incidence of thrombocytopenia (OR: 2.32, p=0.007), heart valve thickening and dysfunction (OR: 9.06, p=0.015) and triple aPL positivity (OR: 1.83, p=0.027), as well as lower levels of C3, C4 and platelets (p-values: <0.001, <0.001 and 0.001) compared to B2-CIC-negative patients. B2-CIC of IgM isotype were significantly more prevalent in gestational than thrombotic APS. Conclusions: Patients with thrombotic events and positive for B2-CIC had lower platelet count and complement levels than those who were negative, suggesting a greater degree of platelet activation.

The role of virus infections in Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is an autoimmune disease with a clinical picture of not only mainly exocrine gland involvement, with dryness symptoms, but also internal organ and systems involvement. The epithelial damage and releasing of antigens, which, in some circumstances, become autoantigens, underlay the pathogenesis of pSS. The activation of autoimmune processes in pSS leads to the hyperactivation of B cells with autoantibody production and other immunological phenomena such as hypergammaglobulinemia, production of cryoglobulins, or formation of extra-nodal lymphoid tissue. Among the risk factors for the development of this disease are viral infections, which themselves can activate autoimmune reactions and influence the host's immune response. It is known that viruses, through various mechanisms, can influence the immune system and initiate autoimmune reactions. These mechanisms include molecular mimicry, bystander activation, production of superantigens-proteins encoded by viruses-or a programming to produce viral cytokines similar to host cytokines such as, e.g., interleukin-10. Of particular importance for pSS are viruses which not only, as expected, activate the interferon pathway but also play a particular role, directly or indirectly, in B cell activation or present tropism to organs also targeted in the course of pSS. This article is an attempt to present the current knowledge of the influence specific viruses have on the development and course of pSS.

The Role of the Microbiome in Sjogren's Syndrome.

The human microbiome is a living ecosystem existing within the host organism, determined by a balance between pathogenic microorganisms, symbionts, and commensals. The disturbance of microbiome composition-dysbiosis-often resulting in the excess of commensal numbers, may push the immune system towards activation of inflammatory and autoimmune processes. Changes in the microbiome of gut, eyes, and mouth may play a significant role in the development and course of autoimmune diseases, including primary Sjogren's syndrome. This autoimmune disease is associated with changes in the protective barrier of the epithelium, which is an important part of the antimicrobial defense. The development of pSS may be influenced by a mechanism of molecular mimicry between microbial antigens and self antigens leading to the initiation of anti-Ro60 antibody response. The knowledge of the influence of the state of microbiome on pSS may translate into the prophylaxis of the progression of dryness symptoms. The aim of this review is to present various aspects related to the human microbiome and Sjogren's syndrome.

The level of TGF-ß in sera of patients with primary Sjögren's syndrome.

OBJECTIVES: Tumor growth factor ß (TGF-ß) is a pleiotropic cytokine which controls autoimmune reactions, cell proliferation, and the organ accumulation of lymphocytes. This cytokine has a protective and anti-inflammatory effect in autoimmune processes, but also has a pro-fibrinous activity. Therefore, its importance in the development of systemic sclerosis has been proven. The role of TGF-ß in Sjögren's syndrome is also a valid direction of research. The aim of the presented study is to evaluate the level of TGF-ß in sera of primary Sjögren's syndrome patients and to investigate possible correlations with autoantibodies, cytokines, and cells in biopsy of minor salivary glands active in the pathogenesis of this syndrome. MATERIAL AND METHODS: Thirty-three primary Sjögren's syndrome patients were included. Routine laboratory tests and immunological assessment (ANA, anti SS-A, anti SS-B antibodies, rheumatoid factor), ophthalmological assessment with ocular staining scoring, chest X-ray, and high-resolution computed tomography (if necessary) were performed. Serum concentrations of cytokines such as TGF-ß, BAFF, APRIL, FLT-3L, LT-α, IL-21, and TNF-α were evaluated using standard ELISA assays. The histopathological evaluation (focus score) and the determination of CD3+, CD4+, CD19+, CD21+, CD35+ cells was performed. RESULTS: There was no significant correlation between TGF-ß and other tested cytokines or autoantibodies, other than TNF-α. A negative correlation (ρ = -0.472) between TGF-ß and TNF-α was found. There were no correlations between TGF-ß and: results of ocular examinations, elements of histopathological variables, or lungs changes. CONCLUSIONS: The authors state that: 1) the results may indicate that TGF-ß influences the serum TNF-α activity in pSS patients, 2) our findings suggest that TGF-ß may be the strongest inhibitor of TNF-α among cytokines involved in pSS pathogenesis, and 3) the results may explain the ineffectiveness of anti-TNF drugs in the treatment of pSS.