Abstract
BackgroundSpecific anti-phospholipids antibodies (aPLs) are used as classification criteria of the antiphospholipid syndrome (APS). These aPLs, although essential for diagnosis, do not predict disease phenotypes, which may require specific therapies. Non-criteria aPLs are rarely evaluated and their role is yet to be defined. In the current study, we aimed to examine the association between criteria and non-criteria aPLs and APS phenotypes.MethodsSerum samples from 188 subjects, 130 APS patients and 58 controls were analyzed for the presence of 20 aPLs (IgG and IgM isotypes to cardiolipin (CL), beta2-glycoprotein1 (β2GP1), phosphatidic acid (P-acid), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidylserine (PS), annexin-5 (AN) and prothrombin (PT) using a line immunoassay (GA Generic Assays, Germany). Sero-positivity to the different aPLs/aPLs profiles was correlated to APS phenotypes (i.e. arterial thrombosis, CNS manifestations, venous thrombosis, relapsing disease, obstetric morbidity).ResultsIn this cohort, arterial thrombosis was associated with accumulative number of ≥ 7/20 aPLs evaluated (OR 4.1; CI 95% 1.9–96, p = 0.001) as well as the sole presence of aPT (IgG) (OR 2.3;CI 95% 1.1–5.1, p = 0.03). CNS manifestations were linked with a profile of 4 aPLs (IgG): aPT, aPG, aPI and aAN (OR 2.6;CI 95% 1.1–6.3, p = 0.03). Symptom-free period of ≥ 3 years was linked with lower number of aPLs and the presence of aPI (IgG) (OR 3.0;CI 95% 1.08–8.1, p < 0.05) or aAN (IgG) (OR 3.4;CI 95% 1.08–10.9, p < 0.05). APS related pregnancy morbidity correlated with a profile of 2 aPLs (IgG): aCL and aPS (OR 2.9; CI 95% 1.3–6.5, p < 0.05) or the sole presence of aAN (IgG) (OR 2.8; CI 95% 1.02–8, p = 0.05).ConclusionIn this study, we observed an association between specific criteria/non-criteria aPLs or aPLs profiles and clinical phenotypes of APS. Our data suggest that examination of a wider variety of aPLs may allow better characterization of APS.
Highlights
Specific anti-phospholipids antibodies are used as classification criteria of the antiphospholipid syndrome (APS)
central nervous system (CNS) manifes‐ tations were linked with a profile of 4 at phospholipids or phospholipid-binding proteins (aPLs) (IgG): aPT, aPG, aPI and aAN
Regarding non-criteria aPLs, the specificity of the test was 100% for the IgM isotype and 95% for the IgG antibodies compared to healthy controls. aPLs were more prevalent among APS patients compared to our entire control groups as well as the healthy and diseased control subjects with sepsis separately (Table 2)
Summary
Specific anti-phospholipids antibodies (aPLs) are used as classification criteria of the antiphospholipid syndrome (APS). Sero-positivity of all threeclassification criteria-aPLs termed the “triple positive”variant is linked with a more aggressive disease [8,9,10] The latter may require specific therapeutic interventions such as enhanced anti-coagulations or addition of other treatment modalities [8, 11,12,13,14,15]. A new technique for aPLs testing was developed, using a line immunoassay (LIA), a multiplex method that permits estimation of a relatively large profile of aPLs concomitantly [6, 22] This novel assay technique appears to discriminate aPLs associated with APS from aPLs detected during infectious diseases and even asymptomatic carriers and may detect specific binding of aβ2GP1 to domain (D1) of the β2GP1 [16, 23,24,25]
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