Closing the Serological Gap in the Antiphospholipid Syndrome: The Value of “Non-criteria” Antiphospholipid Antibodies

Abstract

Objective.Most clinicians use the 2006 Sydney classification criteria to evaluate patients suspected of having antiphospholipid syndrome (APS). Although sensitive and specific for APS, many patients fulfilling clinical criteria for the syndrome are persistently negative for the specific serological tests (“laboratory criteria”). These “seronegative APS” (SN-APS) patients can go undiagnosed and untreated until they experience serious clinical events. This study’s objective was to describe antibody profiles of SN-APS patients using non-criteria markers, assess the clinical utility of these markers separately and in combination, and suggest incorporation into guidelines for patients suspected of APS.Methods.We categorized 175 consecutive patients suspected of APS into 2 subgroups: 107 fulfilling Sydney APS classification for seropositive APS (SP-APS) and 68 with clinical manifestations suggestive of APS but having negative serology, on 2 occasions, for criteria markers (SN-APS). On study inclusion, samples were retested for criteria and 11 non-criteria markers, including antiphosphatidylserine/prothrombin antibodies.Results.Using 4 of 11 non-criteria tests, a cumulative 30.9% of SN-APS patients were detected. Combining results of all 11 non-criteria tests, 25 SN-APS (36.8%) and 89 SP-APS (83.2%) were positive for 1 or more non-criteria antibodies.Conclusion.Failure to diagnose APS can result in severe clinical consequences. Patients displaying clinical features of APS, but negative for conventional criteria markers, should undergo additional testing for non-criteria biomarkers. In our cohort, around one-third of SN-APS patients showed reactivity to 1 or more non-criteria markers. An update to the current classification criteria incorporating new serological markers should be considered to identify and stratify patients with APS for more effective treatment and management.

“Non-criteria” antiphospholipid antibodies add value to antiphospholipid syndrome diagnoses in a large Chinese cohort

“…As to the relationship between aPLs and clinical manifestations, all of the biomarkers explored here are better predictors of late pregnancy morbidity rather than early pregnancy morbidity, supporting the concept that late pregnancy morbidity is a more specific clinical manifestation of the disease. Our results showed a higher prevalence of non-criteria aPL compared with similar studies previously reported [38,40,41]. On the one hand, variability between commercial diagnostic kits and lack of standardization among laboratories may account for the discrepancy.…”

Seronegative antiphospholipid syndrome: refining the value of “non-criteria” antibodies for diagnosis and clinical management

“…The Authors found that one-third of the 'seronegative' sera gave positive results. 24 The study concluded that patients with clinical features of APS, but negative for conventional criteria markers, should undergo additional testing for non-criteria biomarkers. 24 A recent study evidenced that positivity for the extracriteria aPL was <1% in SN-APS (thrombotic or obstetric); however, the lack of clear inclusion and exclusion criteria does not allow a precise estimation of the prevalence to be made.…”

“…24 The study concluded that patients with clinical features of APS, but negative for conventional criteria markers, should undergo additional testing for non-criteria biomarkers. 24 A recent study evidenced that positivity for the extracriteria aPL was <1% in SN-APS (thrombotic or obstetric); however, the lack of clear inclusion and exclusion criteria does not allow a precise estimation of the prevalence to be made. 25 Similarly, non-criteria antibodies were detected in 18.8% of SN-APS patients also in a Chinese cohort composed of APS and patients with only clinical criteria for APS.…”

Immune Complexes of Beta-2-Glycoprotein I and IgA Antiphospholipid Antibodies Identify Patients With Elevated Risk of Thrombosis and Early Mortality After Heart Transplantation

“…Several authors have suggested that the assessment of new autoantibodies can help to identify the syndrome in patients with APS clinic (7)(8)(9)(10). Among the new aPL that have been described associated with APS-events, the IgA aB2GP1 and the anti-phosphatidyl serine/prothrombin (IgG or IgM) are those where a greater association with the APS clinical aspects has been observed (11)(12)(13).…”