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AB0196 Antibodies versus domain I of BETA2-glycoprotein I: A marker of systemic autoimmunity?
  1. C. Nalli1,2,
  2. L. Andreoli3,
  3. G. Norman4,
  4. Z. Shums4,
  5. S. Encabo4,
  6. P.L. Meroni5,
  7. A. Tincani1
  1. 1Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Brescia
  2. 2Rheumatology Chair, University of Pavia, Pavia
  3. 3Rheumatology and Clinical Immunology, University of Brescia, Brescia, Italy
  4. 4INOVA Diagnostics Inc., Instrumentation Laboratory, San Diego, California, United States
  5. 5Internal Medicine, University of Milan, Milan, Italy

Abstract

Background Anti-β2glycoprotein I antibodies (a-β2GPI) are involved in the pathogenesis of the Antiphospholipid Syndrome (APS) and are a formal laboratory criterion for the diagnosis of APS. These antibodies however can be detected in individuals without any manifestation of APS, particularly in patients with systemic autoimmune diseases (SAD), such as Systemic Lupus Erythematosus (SLE), Undifferentiated Connective Tissue Disease (UCTD), Rheumatoid Arthritis (AR), Sjogren Syndrome (SS), Systemic Sclerosis (SSc). Recent studies demonstrated that different domains of a-β2GPI may carry different pathogenic potential. In particular, a-β2GPI IgG antibodies against Domain 1 (D1) appear to be associated with thrombosis and seem to be more specific for APS, where as a-β2GPI IgG antibodies to Domain 4/5 (D4/5) have been associated with various non-thrombotic conditions, such as atherosclerotic syndrome, leprosy and children with no autoimmune diseases.

Objectives To investigate the fine specificity of IgG a-β2GPI in different groups of adults patients.

Methods We studied: A) 59 patients with APS (12 obstetric APS, 47 thrombotic APS); B) 69 patients with SAD (15 UCTD, 32 SLE, 15 AR, 4 SS, 3 SSc) without any thrombotic and/or obstetric event related to APS in their medical history; C) 10 patients with other inflammatory/autoimmune disease (miscellanea): 5 Rheumatic Polymylagia (PMR), 2 Ankylosing Spondylitis, 1 discoid lupus, 2 primary biliary cirrhosis. All subjects were IgG a-β2GPI positive with our routinely performed home-made ELISA assay. IgG a-β2GPI D1 and IgG D4/5 were tested on research ELISAs containing recombinant β2GPI domain antigens (QUANTA Lite™ ELISA, INOVA Diagnostics). Results were considered as optical density (OD) values.

Results Table shows ratio values in each group.

Conclusions The interpretation of a positive result for aPL remains a difficult task, particularly in those patients who do not fulfill APS clinical criteria. A-β2GPI IgG with prevalent specificity for D1 seem to cluster in patients with connettive tissue diseases, including APS, while anti-D4/5 were more represented in patients with Chronic Arthritis or organ-specific autoimmune conditions. Anti-D1 are not limited to patients with thrombosis, but they are rather markers of Systemic Autoimmune Diseases. Their thrombotic potential can be modulated by the presence of a second-hit.

  1. Andreoli L, et al. Ann Rheum Dis. 2011 Feb;70(2):380-3.

  2. De Laat B, et al. J Thromb Haemost 2009;7:1767-73.

  3. De Laat B, et al. Blood 2005;105:1540-45.

Disclosure of Interest C. Nalli: None Declared, L. Andreoli: None Declared, G. Norman Employee of: INOVA Diagnostics Inc., Instrumentation Laboratory, Z. Shums Employee of: INOVA Diagnostics Inc., Instrumentation Laboratory, S. Encabo Employee of: INOVA Diagnostics Inc., Instrumentation Laboratory, P. L. Meroni: None Declared, A. Tincani: None Declared

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