Signs of impaired immunoregulation and enhanced effector T-cell responses in the primary antiphospholipid syndrome

• Published in: Lupus 2016-04, Vol.25 (4), p.389-398
• Main Authors: Jakiela, B, Iwaniec, T, Plutecka, H, Celinska-Lowenhoff, M, Dziedzina, S, Musial, J
• Format: Article
• Language: English
• Subjects: Adult; Antibodies; Antibodies, Antiphospholipid - blood; Antiphospholipid syndrome; Antiphospholipid Syndrome - blood; Antiphospholipid Syndrome - diagnosis; Antiphospholipid Syndrome - immunology; Autoimmune diseases; Biomarkers - blood; Case-Control Studies; Cells, Cultured; Cytokines; Down-Regulation; Effector cells; Female; Flow cytometry; Foxp3 protein; Helper cells; Humans; Immunoglobulin G; Immunoglobulin G - blood; Immunophenotyping; Immunoregulation; Inflammation; Interleukin 10; Interleukin 2; Isoforms; Latency; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - diagnosis; Lupus Erythematosus, Systemic - immunology; Lymphocytes T; Male; Middle Aged; Phenotype; Serum levels; Systemic lupus erythematosus; T cell receptors; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Transforming Growth Factor beta1 - blood; Transforming growth factor-b1
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/0961203315618267

Introduction We investigated whether primary antiphospholipid syndrome (PAPS) is characterized by a deficiency in immunoregulatory pathways, a phenomenon recently implicated in the pathogenesis of autoimmune diseases. Methods Serum levels of immunoregulatory (e.g. IL-10 and TGF-β1) and proinflammatory (e.g. IL-17A) cytokines were measured in PAPS, systemic lupus erythematosus (SLE) with secondary APS (SAPS), or without APS, and in healthy controls (n = 40 in each group). In a subgroup of PAPS patients we also compared phenotype and function (flow cytometry) of regulatory T-cells (Treg) and cytokine production by effector T-cells. Results Our major finding was decreased levels of TGF-β1 in PAPS and SAPS as compared to SLE without APS and controls. TGF-β1 was the lowest in PAPS patients showing high levels of aPL IgG with significant negative correlation with the titer. SLE patients were characterized by lower serum levels of IL-2 and increased IL-17A, as compared to the other groups. The numbers of circulating Treg cells and their phenotype (e.g. FoxP3 isoforms) were not disturbed in PAPS. However, surface expression of latency associated peptide (binds TGF-β) in activated FoxP3 + cells and in vitro production of TGF-β1 were decreased in PAPS patients with high titers of aPL IgG. Moreover, frequencies of cytokine producing effector T-helper cells (including Th17) were significantly elevated in this group. Conclusions PAPS patients with high titers of aPL IgG antibodies were characterized by decreased systemic levels of TGF-β1 and its impaired production in vitro, suggesting impaired immunoregulation and enhanced adaptive autoimmune responses leading to the production of aPL antibodies.