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Volume 14
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10.3390/jcm14207164
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Review

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

by
Monika Očková
1,
Ariadna Anunciación-Llunell
1,
Catalina Andrada
1,
Enrique Esteve-Valverde
2,
Francesc Miró-Mur
1,* and
Jaume Alijotas-Reig
1,3,4,*
1
Systemic Autoimmune Diseases Research Unit, Vall d’Hebron Institut de Recerca (VHIR), Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
2
Department of Internal Medicine, Hospital Sant Camil, Consorci Sanitari del Garraf, 08810 Barcelona, Spain
3
Department of Internal Medicine, Hospital Universitari Vall d’Hebron (HUVH), Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
4
Department of Medicine, Universitat Autònoma de Barcelona (UAB), Vall d’Hebron Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(20), 7164; https://doi.org/10.3390/jcm14207164 (registering DOI)
Submission received: 2 September 2025 / Revised: 29 September 2025 / Accepted: 6 October 2025 / Published: 11 October 2025
(This article belongs to the Special Issue Antiphospholipid Syndrome: Clinical Advances in Diagnosis and Management)
Review Reports Versions Notes

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 (Jan 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.
Keywords: antiphospholipid syndrome; antiphospholipid antibodies; diagnosis; prevalence; obstetric manifestations; thrombotic manifestations; non-criteria aPL antiphospholipid syndrome; antiphospholipid antibodies; diagnosis; prevalence; obstetric manifestations; thrombotic manifestations; non-criteria aPL

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MDPI and ACS Style

Očková, M.; Anunciación-Llunell, A.; Andrada, C.; Esteve-Valverde, E.; Miró-Mur, F.; Alijotas-Reig, J. IgM Antiphospholipid Antibodies in Antiphospholipid Syndrome: Prevalence, Clinical Associations, and Diagnostic Implications—A Scoping Review. J. Clin. Med. 2025, 14, 7164. https://doi.org/10.3390/jcm14207164

AMA Style

Očková M, Anunciación-Llunell A, Andrada C, Esteve-Valverde E, Miró-Mur F, Alijotas-Reig J. IgM Antiphospholipid Antibodies in Antiphospholipid Syndrome: Prevalence, Clinical Associations, and Diagnostic Implications—A Scoping Review. Journal of Clinical Medicine. 2025; 14(20):7164. https://doi.org/10.3390/jcm14207164

Chicago/Turabian Style

Očková, Monika, Ariadna Anunciación-Llunell, Catalina Andrada, Enrique Esteve-Valverde, Francesc Miró-Mur, and Jaume Alijotas-Reig. 2025. "IgM Antiphospholipid Antibodies in Antiphospholipid Syndrome: Prevalence, Clinical Associations, and Diagnostic Implications—A Scoping Review" Journal of Clinical Medicine 14, no. 20: 7164. https://doi.org/10.3390/jcm14207164

APA Style

Očková, M., Anunciación-Llunell, A., Andrada, C., Esteve-Valverde, E., Miró-Mur, F., & Alijotas-Reig, J. (2025). IgM Antiphospholipid Antibodies in Antiphospholipid Syndrome: Prevalence, Clinical Associations, and Diagnostic Implications—A Scoping Review. Journal of Clinical Medicine, 14(20), 7164. https://doi.org/10.3390/jcm14207164

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