title: Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review.
abstract: 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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: UCG de Reumatología, Instituto de Investigación Biomédica en Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Spain.
authors.forename: Veronica
authors.initials: V
authors.lastname: Rodríguez-García
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, Department of Medicine, Rayne Institute, 5 University Street and Arthritis Research UK Centre for Adolescent Rheumatology, University College London, London, UK.
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Ioannou
authors.affiliation: UCG de Reumatología, Instituto de Investigación Biomédica en Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernández-Nebro
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, Department of Medicine, Rayne Institute, 5 University Street and.
authors.forename: David A
authors.initials: DA
authors.lastname: Isenberg
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, Department of Medicine, Rayne Institute, 5 University Street and i.giles@ucl.ac.uk.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Giles
mesh_terms: D017304:Annexin A5 / Q000097:blood / Q000276:immunology; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000276:immunology*; D016022:Case-Control Studies; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D010743:Phospholipids / Q000276:immunology*; D015995:Prevalence; D012189:Retrospective Studies; D053482:beta 2-Glycoprotein I / Q000097:blood / Q000276:immunology
chemical_list: D017304:Annexin A5; D000888:Antibodies, Anti-Idiotypic; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010743:Phospholipids; D053482:beta 2-Glycoprotein I
keywords: anti-phospholipid antibodies; anti-phospholipid syndrome; new assays; non-criteria