IgM antiphospholipid antibodies are associated with a microvascular phenotype in antiphospholipid syndrome

Background: The clinical significance of IgM antiphospholipid antibodies (aPL) in antiphospholipid syndrome (APS) remains uncertain, while lupus anticoagulant is a well-established marker for thrombotic risk. Methods: The objective of the study is to evaluate the impact of IgM aPL on the clinical phenotype of primary APS (PAPS). In this retrospective multicenter study, patients meeting updated Sapporo classification criteria were categorized into three aPL profiles: isolated lupus anticoagulant (isolated-LA), isolated IgM anticardiolipin and/or IgM anti-β2-glycoprotein I antibodies (isolated-IgM-aPL), and LA and IgM antibodies (LA + IgM-aPL). Clinical features were compared between isolated-LA vs. isolated-IgM-aPL and isolated-LA vs. LA + IgM-aPL groups. Results: Among 202 patients, 17 (8.4%) had isolated-IgM-aPL, 145 (71.7%) isolated-LA, and 40 (19.8%) LA + IgM-aPL. Compared to isolated-LA, the isolated-IgM-aPL group had lower female prevalence (41.2% vs. 65.5%; p = 0.049), fewer venous thromboses (41.2% vs. 66%; p = 0.049), but more obstetric morbidity (58.8% vs. 26.2%; p = 0.005). There was a higher proportion of patients with livedo racemosa (47.1% vs. 20.7%; p = 0.015) and with white matter lesions (WML) (29.4% vs. 9.7%; p = 0.020) in the isolated-IgM-aPL group. In the multivariate analysis, WML remained independently associated (OR 3.7; p = 0.020). In the second comparison (isolated-LA vs. LA + IgM-aPL), a higher prevalence of livedoid vasculopathy (15.0% vs. 4.8%; p = 0.026) and WML (22.5% vs. 9.7%; p = 0.037) were observed in the LA + IgM-aPL group. Nonetheless, no independent associations were seen in the multivariate analysis. Conclusion: IgM aPL may be associated with a distinct APS phenotype characterized by microvascular involvement, including livedo and WML. These findings support the need for further research into the clinical implications of IgM isotype positivity in APS.