Relevance of isolated IgM antiphospholipid antibodies in a longitudinal cohort of antiphospholipid syndrome.

Abstract

IgM aCL and anti-β2 glycoprotein I (aβ2GPI) positivity have been downgraded in the current classification criteria for APS. We assessed the clinical relevance of IgM aPL in APS. A 5-year longitudinal study was conducted in 186 individuals: 54 aPL carriers, 83 with thrombotic APS (TAPS), and 49 with obstetric APS (OAPS). Patient enrolment was based on the Sydney classification criteria. aPL thresholds for the chemiluminescence immunoassay and ELISA were established using a cohort of 250 healthy donors. In the APS cohort (n = 132), at the time of patient enrolment, 23.5% (31/132) and 37.1% (49/132) of patients were positive for aβ2GPI and aCL, respectively. IgM-only positivity was observed in 45.2% (14/31) of aβ2GPI-positive patients and in 38.8% (19/49) of those positive for aCL. Isotype switching from IgM to IgG occurred in 28.6% (4/14) of aβ2GPI IgM-only positive patients and in 10.5% (2/19) of aCL IgM-only positive patients. The time interval to IgG isotype switching exceeded 3 years for both aPL specificities. IgM aPL prevalence was significantly higher in OAPS than in TAPS [47% (23/49) vs 19% (16/83), P = 0.0014), but similar between aPL-carriers and APS patients [22% (12/54) vs 30% (39/132), P = 0.37]. Importantly, 8% (11/132) of APS patients were positive only for IgM aPL, of whom 82% (9/11) had OAPS with a history of severe preeclampsia or placental insufficiency. The number of mature B cells in APS patients was comparable between aCL/aβ2GPI IgM-only-positive and aCL/aβ2GPI IgG-only-positive patients. Relying solely on IgG may underclassify patients with APS.