title: Signs of impaired immunoregulation and enhanced effector T-cell responses in the primary antiphospholipid syndrome.
abstract: BACKGROUND
  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.
authors.affiliation: Jagiellonian University Medical College, Department of Medicine, Krakow, Poland mmmusia@cyf-kr.edu.pl.
authors.forename: B
authors.initials: B
authors.lastname: Jakiela
authors.affiliation: Jagiellonian University Medical College, Department of Medicine, Krakow, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Iwaniec
authors.affiliation: Jagiellonian University Medical College, Department of Medicine, Krakow, Poland.
authors.forename: H
authors.initials: H
authors.lastname: Plutecka
authors.affiliation: Jagiellonian University Medical College, Department of Medicine, Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Celinska-Lowenhoff
authors.affiliation: Jagiellonian University Medical College, Department of Medicine, Krakow, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Dziedzina
authors.affiliation: Jagiellonian University Medical College, Department of Medicine, Krakow, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Musial
mesh_terms: D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000097:blood*
chemical_list: D017152:Antibodies, Antiphospholipid; D015415:Biomarkers; D007074:Immunoglobulin G; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: Primary antiphospholipid syndrome; immunoregulation; regulatory T-cells; transforming growth factor-β