923dca9fbc049dd31fd1afef073e1234 jcm-14-07164-v3.pdf 9a1d85ce4599dd4ac16ec08904fb39df201f1c77 jcm-14-07164-v3.pdf 64758a295e590297d39663a1445e963a36c505685d6030cad02c2951675737b1 jcm-14-07164-v3.pdf Title: IgM Antiphospholipid Antibodies in Antiphospholipid Syndrome: Prevalence, Clinical Associations, and Diagnostic Implications—A Scoping Review Subject: 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, a2GPI, 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 a2GPI-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% a2GPI-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, a2GPI, 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 Author: Monika Očková, Ariadna Anunciación-Llunell, Catalina Andrada, Enrique Esteve-Valverde, Francesc Miró-Mur and Jaume Alijotas-Reig Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Mon Oct 13 08:15:36 2025 CEST ModDate: Mon Oct 13 08:24:11 2025 CEST Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1545511 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- XLGPFE+URWPalladioL-Ital Type 1 Custom yes yes yes 148 0 HRLGRA+URWPalladioL-Bold Type 1 Custom yes yes yes 149 0 IGAEKB+VnURWPalladioL Type 1 Custom yes yes yes 150 0 SKNLNK+URWPalladioL-Roma Type 1 Custom yes yes yes 151 0 LWLIVD+EURM10 Type 1 Builtin yes yes yes 152 0 EILUJF+CMSY10 Type 1 Builtin yes yes yes 215 0 DBOONN+PalatinoLinotype TrueType WinAnsi yes yes no 209 0 DBOONN+PalatinoLinotype TrueType WinAnsi yes yes no 260 0 DBOONL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 261 0 HHFREY+EURM7 Type 1 Builtin yes yes yes 320 0 CTGVMV+EURB7 Type 1 Builtin yes yes yes 321 0 MWRHMH+EURM5 Type 1 Builtin yes yes yes 352 0 QGOZZF+EURB5 Type 1 Builtin yes yes yes 353 0 DBOONN+PalatinoLinotype TrueType WinAnsi yes yes no 480 0 DBOONN+PalatinoLinotype TrueType WinAnsi yes yes no 624 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-11-12 03:09:31 CET RepresentationInformation: jcm-14-07164-v3.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-11-11 14:04:38 CET Size: 1545511 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 994 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Methodology Children: Item: Title: Eligibility Criteria Item: Title: Information Sources and Search Strategy Item: Title: Selection Process Item: Title: Data Charting Item: Title: Synthesis of Results Item: Title: Methodological Shortcuts and Implications Item: Title: Results Children: Item: Title: Prevalence of aPL IgM Isotype Across Clinical Manifestations Children: Item: Title: Obstetric Manifestations Item: Title: Combined Thrombotic and Obstetric Manifestations Item: Title: Purely Thrombotic Manifestations Item: Title: Thrombotic and Other Manifestations Item: Title: Cerebrovascular Manifestations Item: Title: Associations of IgM aPL with Clinical Manifestations Children: Item: Title: Obstetric Manifestations Item: Title: Thrombotic and Vascular Manifestations Item: Title: New Approach to aPL Associations: Cluster Analysis Item: Title: Factors Contributing to Thrombosis: Neutrophil Activation and NETosis Item: Title: Discussion Item: Title: Conclusions Item: Title: Future Perspectives Item: Title: References Info: Title: IgM Antiphospholipid Antibodies in Antiphospholipid Syndrome: Prevalence, Clinical Associations, and Diagnostic Implications—A Scoping Review Author: Monika Očková, Ariadna Anunciación-Llunell, Catalina Andrada, Enrique Esteve-Valverde, Francesc Miró-Mur and Jaume Alijotas-Reig Subject: 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, a2GPI, 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 a2GPI-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% a2GPI-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, a2GPI, 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. 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