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THU0345 Presence of Immunoglobulin (IG) A Antibodies against Cardiolipin and β2-Glycoprotein-I in The Absence of IGG and IGM in Systemic Lupus Erythematosus
  1. M. Frodlund,
  2. J. Wetterö,
  3. T. Skogh,
  4. C. Sjöwall
  1. IKE, Faculty of Health Sciences, Linköping University, Linköping, Sweden

Abstract

Background The antiphospholipid (Hughes) syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity and twice repeated confirmed presence of anti-cardiolipin and/or anti-β2-glycoprotein-I antibodies of IgM/IgG isotype and/or a positive lupus anticoagulant test. These tests and isotypes are found in the 1997 update of the American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE). As antiphospholipid antibodies are associated with increased morbidity and mortality in SLE, it is of major concern to screen new patients early for these antibodies. Despite limited scientific evidence, however, IgA isotype was added as a formal laboratory criterion in the 2012 SLICC criteria.

Objectives Herein, we thus evaluated a well-characterized Swedish SLE cohort with regard to the presence of IgM, IgA and IgG isotypes of anti-cardiolipin or anti-β2-glycoprotein-I antibodies in relation to disease phenotype, organ damage, smoking habits, medical treatment, APS and thromboembolic events. We aimed to define the frequency of each isotype separately in order to disclose if any specific features are associated with the presence of isolated IgA antiphospholipid antibodies.

Methods Serum samples from 254 patients (88% women) of the “Clinical Lupus Register in Northeastern Gothia” were included. All cases had a clinical diagnosis of SLE and met the 1982 ACR classification criteria and/or the Fries' diagnostic principle (i.e. positive ANA + manifestations in ≥2 typical organ systems). 211 (83%) were prevalent cases, whereas 43 (17%) had a newly diagnosed SLE at the time for blood sampling. 200 healthy blood donors and 100 patients with early rheumatoid arthritis (RA) served as controls. Anti-cardiolipin and anti-β2-glycoprotein-I antibodies (IgM, IgA and IgG) were analyzed at Linköping Clinical immunology unit using a fluoroenzyme-immunoassay (Phadia-250 instrument, Thermo-Fisher Scientific Phadia AB, Uppsala, Sweden). Cut-off limits for positive antibody tests were set at >99th percentile of healthy blood donors.

Results Among the SLE patients: 45 (18%) fulfilled APS classification; 69 (27%) were positive for at least one isotype (IgM/IgA/IgG) and 34 (13%) for IgA of either anti-cardiolipin or anti-β2-glycoprotein-I antibody. 24 (9%) SLE cases were positive for IgA anti-cardiolipin, 12 of whom were positive in the absence of IgM/IgG class antibodies. 28 (11%) SLE cases were positive for IgA anti-β2-glycoprotein-I, 13 of whom were positive in the absence of IgM/IgG. 7 (2.8%) SLE patients were positive for isolated IgA anti-cardiolipin and/or anti-β2-glycoprotein-I antibodies and fulfilled APS classification, whereas 9 SLE cases (3.5%) were positive for isolated IgA anti-cardiolipin and/or anti-β2-glycoprotein-I antibodies without meeting APS classification. 7% of the RA cases were positive with regard to at least one isotype of anti-cardiolipin or anti-β2-glycoprotein-I antibodies.

Conclusions We demonstrate that IgA anti-cardiolipin and/or anti-β2-glycoprotein-I antibodies can be found in almost 1/7 of Swedish SLE patients, either in the absence of IgM/IgG (47%) or in combination with other isotypes (53%). In 7 of these cases, the presence of isolated IgA antiphospholipid antibodies was associated with APS. Analyses of associations with disease outcome, phenotype, drugs and smoking habits are ongoing.

Disclosure of Interest None declared

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