IgM Antiphospholipid Antibodies in Antiphospholipid Syndrome : Prevalence, Clinical Associations, and Diagnostic Implications-A Scoping Review

Background : IgM antiphospholipid antibodies (aPL) were de-emphasised in the 2023 ACR/EULAR criteria, yet their precise clinical significance remains uncertain. Methods : A rapid scoping review of PubMed (January 2000-June 2025) identified original human studies reporting IgM aCL, aβGPI, or aPS/PT prevalence or outcomes; 40 studies met the eligibility criteria. Prevalence and odds ratios (ORs) of clinical associations were extracted. Results : IgM aPL are common across APS phenotypes. Obstetric cohorts showed aCL-IgM prevalences of 3-82%, often equal to or exceeding those of IgG, while aβGPI-IgM reached a prevalence of 2-63%. In mixed thrombotic-obstetric cohorts, aPS/PT-IgM was the most frequent isotype (31-79%). Purely thrombotic studies still reported 0-59% aβGPI-IgM, with PS/PT-IgM at 55% and 62% in two large series. Significant outcome signals from clinical associations of IgM aPL were inconsistent but noteworthy in (i) pregnancy loss for high-titre aCL, aβGPI, and aPS/PT, (ii) thrombosis driven by aPS/PT and (iii) organ-specific arterial events (retinal thrombosis and stroke) in isolated IgM phenotypes. Conclusions : The role of aPL-IgM remains uncertain. The findings advocate for a nuanced approach to IgM interpretation, supporting its reconsideration in specific clinical settings and emphasising the significance of ongoing research into the mechanistic and prognostic utility of IgM aPL.