Seronegative antiphospholipid syndrome

Rheumatology (Oxford). 2013 Aug;52(8):1358-67. doi: 10.1093/rheumatology/ket126. Epub 2013 Mar 15.

Abstract

APS is an autoimmune disease that leads to arterial and/or venous thrombosis, recurrent pregnancy loss and persistently positive aPLs. Patients with clinical manifestations highly suggestive of APS but persistently negative conventional aPLs are classified as having seronegative APS. Ongoing research has revealed the existence of non-criteria antibodies proposed to be relevant to APS and that can be potentially included in the disease's classification criteria. We present a literature review on the most promising antibodies of this heterogeneous aPL family, which includes antibodies to a zwitterionic phospholipid, namely phosphatidylethanolamine, phospholipid-binding plasma proteins, phospholipid-protein complexes and anionic phospholipids other than cardiolipin. Although these molecules can increase the diagnostic yield of APS, their clinical relevance is still debatable and needs to be confirmed by interlaboratory efforts toward standardizing diagnostic tools, in addition to experimental data and larger longitudinal studies.

Keywords: anti-β2 glycoprotein I antibodies; antiphospholipid antibodies; antiphospholipid syndrome; phosphatidylethanolamine; pregnancy morbidity; seronegative antiphospholipid syndrome; thrombosis.

Publication types

  • Review

MeSH terms

  • Annexin A5 / immunology
  • Antibodies, Antiphospholipid / blood
  • Antibodies, Antiphospholipid / immunology*
  • Antibody Specificity
  • Antiphospholipid Syndrome / diagnosis
  • Antiphospholipid Syndrome / immunology*
  • Cardiolipins / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Phosphatidylethanolamines / immunology*
  • Pregnancy
  • Pregnancy Complications, Hematologic / immunology
  • Prognosis
  • Risk Assessment
  • Serologic Tests
  • Severity of Illness Index
  • beta 2-Glycoprotein I / immunology*

Substances

  • Annexin A5
  • Antibodies, Antiphospholipid
  • Cardiolipins
  • Immunoglobulin G
  • Immunoglobulin M
  • Phosphatidylethanolamines
  • beta 2-Glycoprotein I
  • phosphatidylethanolamine