Journal of translational autoimmunity · 2026
Anti-Annexin A5 antibodies and Annexin A5 resistance in antiphospholipid syndrome: A systematic review and meta-analysis.
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Alamlih Laith, Becetti Karima, Al Emadi Samar, Satti Eman, Tag Zahir M, Chemaitelly Hiam, Abu-Tineh Mohammad, Abufaied Mohamad, Laws Sa'ad, Khamashta Munther
Аннотация
OBJECTIVE: To provide an updated systematic review and meta-analysis of the estimated pooled of anti-Annexin A5 antibodies (AnxA5-Abs) and Annexin A5 resistance (A5R) across antiphospholipid syndrome (APS) phenotypes.
METHODS: PubMed, EMBASE, and the Cochrane Library were searched from inception to June 2018 and updated in August 2025. Eligible studies included adults tested for AnxA5-Abs (IgG/IgM) and/or A5R who fulfilled revised Sapporo/Sydney APS clinical criteria. Pooled prevalences were estimated using Freeman-Tukey random-effects models and stratified by phenotype, serologic status, and autoimmune disease. Univariable and multivariable meta-regression evaluated predictors of IgG AnxA5-Abs and A5R. The protocol was registered in PROSPERO (CRD42018099462).
RESULTS: Fifty-eight studies were included, comprising 6960 patients and 2417 controls. In obstetric APS cohorts, pooled IgG AnxA5-Abs prevalence was 21.2% (95% CI 7.4-39.2) versus 4.0% (1.7-7.1) in controls; thrombotic APS showed 10.3% (5.7-15.8). IgM AnxA5-Abs were less frequent and showed weaker associations. IgG AnxA5-Abs prevalence was higher in seropositive APS (27.1%) and seronegative APS (20.4%) than in mixed/unstratified APS (11.7%). Among systemic lupus erythematosus (SLE) patients with APS-related clinical manifestations, IgG AnxA5-Abs prevalence was 31.7% versus 16.3% in SLE controls without clinical APS manifestations. A5R prevalence was higher in obstetric (29.9%) and thrombotic APS (28.8%) than in controls (17.5%). Obstetric APS independently predicted higher IgG AnxA5-Abs prevalence.
CONCLUSION: IgG AnxA5-Abs and A5R are enriched in Sapporo-defined obstetric APS, with weaker and less consistent associations in thrombosis-only APS. These findings support the biological plausibility of AnxA5 disruption in obstetric APS and identify AnxA5-related biomarkers as promising candidates for future validation. However, prospective external validation using standardized assays, pre-specified thresholds, and demonstration of incremental prognostic value are essential prerequisites before clinical risk stratification use.
METHODS: PubMed, EMBASE, and the Cochrane Library were searched from inception to June 2018 and updated in August 2025. Eligible studies included adults tested for AnxA5-Abs (IgG/IgM) and/or A5R who fulfilled revised Sapporo/Sydney APS clinical criteria. Pooled prevalences were estimated using Freeman-Tukey random-effects models and stratified by phenotype, serologic status, and autoimmune disease. Univariable and multivariable meta-regression evaluated predictors of IgG AnxA5-Abs and A5R. The protocol was registered in PROSPERO (CRD42018099462).
RESULTS: Fifty-eight studies were included, comprising 6960 patients and 2417 controls. In obstetric APS cohorts, pooled IgG AnxA5-Abs prevalence was 21.2% (95% CI 7.4-39.2) versus 4.0% (1.7-7.1) in controls; thrombotic APS showed 10.3% (5.7-15.8). IgM AnxA5-Abs were less frequent and showed weaker associations. IgG AnxA5-Abs prevalence was higher in seropositive APS (27.1%) and seronegative APS (20.4%) than in mixed/unstratified APS (11.7%). Among systemic lupus erythematosus (SLE) patients with APS-related clinical manifestations, IgG AnxA5-Abs prevalence was 31.7% versus 16.3% in SLE controls without clinical APS manifestations. A5R prevalence was higher in obstetric (29.9%) and thrombotic APS (28.8%) than in controls (17.5%). Obstetric APS independently predicted higher IgG AnxA5-Abs prevalence.
CONCLUSION: IgG AnxA5-Abs and A5R are enriched in Sapporo-defined obstetric APS, with weaker and less consistent associations in thrombosis-only APS. These findings support the biological plausibility of AnxA5 disruption in obstetric APS and identify AnxA5-related biomarkers as promising candidates for future validation. However, prospective external validation using standardized assays, pre-specified thresholds, and demonstration of incremental prognostic value are essential prerequisites before clinical risk stratification use.