Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review

Rheumatology (Oxford). 2015 Nov;54(11):2042-50. doi: 10.1093/rheumatology/kev226. Epub 2015 Jul 7.


Objective: To systematically review and establish the prevalence of antibody positivity in assays not currently included in the APS classification criteria to detect antibodies directed against other phospholipids (PLs), PL binding proteins, coagulation factors and a mechanistic test for resistance of Annexin A5 (AnxA5) anticoagulant activity in APS and control populations.

Methods: We searched PubMed and EMBASE using the key words APS, antiphospholipid antibodies, non-criteria, new assays, IgA anticardiolipin antibodies, lupus anticoagulant, anti-Domain I, IgA anti-β2-glycoprotein I antibodies, antiphosphatidylserine, anti-phosphatidylethanolamine, anti-phosphatidic acid, antiprothrombin, antiphosphatidylserine-prothtombin, anti-vimentin/cardiolipin complex and Annexin A5 resistance. Studies that met inclusion criteria to describe prevalence of non-criteria aPLs in APS patients (n > 10), disease and healthy control subjects were systematically examined.

Results: We selected 16 retrospective studies of 1404 APS patients, 1839 disease control and 797 healthy controls. The highest prevalence of non-criteria aPLs in the largest number of patients with APS was found in IgA anti-β2GPI studies (129/229, 56.3%), AnxA5R (87/163, 53.4%) and IgG anti-Domain I (241/548, 44.0%).

Conclusion: Our finding of a significantly high prevalence of all non-criteria aPLs studied in patients with APS compared with controls was tempered by wide variation in sample size, retrospective collection, assay methodology and different determination of positivity. Therefore, prospective studies of sufficient size and appropriate methodology are required to evaluate the significance of these assays and their utility in the management of patients with APS.

Keywords: anti-phospholipid antibodies; anti-phospholipid syndrome; new assays; non-criteria.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Annexin A5 / blood
  • Annexin A5 / immunology
  • Antibodies, Anti-Idiotypic / blood*
  • Antiphospholipid Syndrome / blood*
  • Antiphospholipid Syndrome / immunology*
  • Case-Control Studies
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Phospholipids / immunology*
  • Prevalence
  • Retrospective Studies
  • beta 2-Glycoprotein I / blood
  • beta 2-Glycoprotein I / immunology


  • Annexin A5
  • Antibodies, Anti-Idiotypic
  • Immunoglobulin A
  • Immunoglobulin G
  • Phospholipids
  • beta 2-Glycoprotein I