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

## TL;DR

This review explores the role of IgM antiphospholipid antibodies in antiphospholipid syndrome, highlighting their prevalence and potential clinical significance.

## Contribution

The study provides a comprehensive analysis of IgM aPL's clinical associations and diagnostic implications, calling for a nuanced interpretation.

## Key findings

- IgM aPL are common in various antiphospholipid syndrome phenotypes, often with high prevalence rates.
- High-titre IgM aCL, aβ2GPI, and aPS/PT are associated with pregnancy loss and thrombosis.
- Isolated IgM phenotypes are linked to organ-specific arterial events like retinal thrombosis and stroke.

## Abstract

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, aβ2GPI, 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 aβ2GPI-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% aβ2GPI-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, aβ2GPI, 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.