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Publication Detail
Profiling Sub-Types of Anti-β2 Glycoprotein I and Anti-Domain I Antibodies May Distinguish Between Different Clinical Phenotypes of the Antiphospholipid Syndrome
  • Publication Type:
    Conference
  • Authors:
    Pericleous C, Garza-Garcia A, Murfitt L, Driscoll P, Isenberg D, Pierangeli S, Ioannou Y, Rahman A
  • Name of conference:
    American College of Rheumatology 2011
  • Conference place:
    Chicago, Illinois
  • Conference start date:
    01/11/2011
  • Conference finish date:
    01/11/2011
Abstract
Background/Purpose: Laboratory classification criteria for the antiphospholipid syndrome (APS) include the quantification of IgG and IgM, but not IgA anticardiolipin (aCL) and anti-β2 glycoprotein I (aβ2GPI) antiphospholipid antibodies (aPL), though recent studies suggest a possible role for IgA. These assays do not reliably differentiate patients with a history of vascular thrombosis (VT) from those with pregnancy morbidity (PM). Of the five domains of β2GPI, pathogenic IgG aPL are considered to target Domain I (DI). We have developed a direct anti-DI ELISA using bacterially expressed DI. Here we investigate whether IgG, IgM and IgA anti-DI levels correlate with IgG, IgM and IgA anti-β2GPI and which of these tests correlate best with clinical phenotypes. Method: We used 9 different ELISAs (IgG/IgM/IgA for each of aCL, aβ2GPI and aDI) to test 158 serum samples - 46 from patients with APS (F:M 41:5, mean age 46.4±12.1); 77 with SLE but not APS (F:M 72:5, mean age 38.8±11.3); and 35 healthy controls (HC) (F:M 23:12, mean age 30.8±7.4). Of 46 APS subjects, 21 suffered VT only, 12 PM only, and 13 both. IgG/IgM aCL activity was defined as GPLU/MPLU respectively. For all remaining assays, results were expressed in units of activity by reference to an in-house standard. Univariate analysis was performed using one-way ANOVA to determine which assay(s) best differentiate APS from SLE and HC, and whether any were associated with the VT or PM phenotypes within APS. Result: 7 of 9 assays gave significantly higher antibody titers in APS compared to SLE and HC (p<0.0001 in each case). The exceptions were IgM aCL (high in both APS and SLE) and IgA aDI (few positive samples). For 3 of these 7 assays, titers were raised in SLE compared to HC, thus only 4 assays (IgG/IgM/IgA aβ2GPI and IgG aDI) selectively recognized APS-derived sera. In the APS group, there was a strong correlation between aβ2GPI and aDI for IgG (p=0.003, r=0.5858) and IgA (p<0.0001, r=0.8603) but not IgM. In contrast, there were no correlations between aβ2GPI and aDI in the SLE group. Although none of the aβ2GPI assays nor IgG aDI could discriminate between patients with VT compared to PM, IgM aDI was found to be associated with PM (p<0.0001) and IgA aDI with VT (p≤0.01). Conclusion: To our knowledge, this is the first study to measure IgG/IgM/IgA aPL against CL, β2GPI and DI simultaneously. aβ2GPI of all isotypes and IgG aDI were found to be most specific for APS. The correlation between aβ2GPI and aDI in APS, but not non-APS subjects supports the idea that pathogenic aβ2GPI bind specifically to DI. The finding that IgA and IgM aDI show specific associations with VT and PM respectively is interesting but needs to be repeated in larger studies.
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