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2026, Vol: 10, Issue: 3
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Review Article
Online Published: 22 Jan 2026
 


Recurrent pregnancy loss and antiphospholipid syndrome: a systematic review of novel autoantibodies and immunological pathways

‏yousef Mohammed Elamin Ali Mohammed, Nora Alhussein Ali Almonawar, Mohammed Fareed A Alasmari, Abdulaziz Awad Alqarni, Mohammed Saeed Algadmi, Faisal Ali M. Alshahrani, Maha Saeed Alzahrani, Aisha Mofareh Almarir, Naif Ahmed Alasiri, Lama Khalid Alnahdi, Amal Mohammad Alahmari, Ali Yahya Alshehri.


Abstract
Background: Recurrent pregnancy loss (RPL) remains a significant clinical challenge, with antiphospholipid syndrome (APS) being a major treatable autoimmune cause. Traditional models focused on thrombosis, but evidence now highlights direct inflammatory and immunological insults at the maternal-fetal interface. A substantial number of patients with obstetric APS phenotypes are seronegative by standard criteria, suggesting a role for novel autoantibodies and immune pathways. Objective: This systematic review aimed to synthesize recent evidence on novel autoantibodies, genetic factors, and immunological pathways involved in the pathogenesis of RPL associated with APS. Methods: Following PRISMA guidelines, a systematic search of five databases (PubMed/MEDLINE, Scopus, Web of Science, Embase, Cochrane) was conducted for studies published between January 2019 and December 2024. Studies investigating non-criteria antibodies, genetic polymorphisms, or novel immunological mechanisms in RPL with/without APS were included. Data extraction and risk-of-bias assessment were performed independently by two reviewers. A narrative synthesis was conducted due to study heterogeneity. Results: From 688 screened records, four studies met the inclusion criteria. The findings revealed a multi-layered pathophysiology: 1) Genetic susceptibility via polymorphisms in APOH and NCF1genes; 2) Cellular dysfunction mediated by the long non-coding RNA LncNR_040117 through MAPK pathway activation, impairing trophoblast function; 3) Specific antibody effects, where anti-β2GPI IgG was independently associated with systemic vascular endothelial dysfunction; and 4) Dysregulated inflammatory networks involving cytokines such as TNF-α and IL-6. Conclusion: The pathogenesis of APS-related RPL extends beyond thrombosis, involving a complex interplay of genetic predisposition, novel antibody specificities, non-coding RNA regulation, and inflammatory cytokine networks. These insights advocate for a paradigm shift towards a more integrated, immune-centric model and highlight potential novel biomarkers and therapeutic targets for improving diagnosis and outcomes in RPL.

Key words: Recurrent Pregnancy Loss, Antiphospholipid Syndrome, Non-Criteria Antiphospholipid Antibodies, Immunological Pathways, Genetic Polymorphisms, Long Non-Coding RNA, Endothelial Dysfunction, Trophoblast


 
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How to Cite this Article
Pubmed Style

Mohammed MEA, Almonawar NAA, Alasmari MFA, Alqarni AA, Algadmi MS, Alshahrani FAM, Alzahrani MS, Almarir AM, Alasiri NA, Alnahdi LK, Alahmari AM, Alshehri AY. Recurrent pregnancy loss and antiphospholipid syndrome: a systematic review of novel autoantibodies and immunological pathways. IJMDC. 2026; 10(3): 1026-1035. doi:10.24911/IJMDC.51-1767548421

Web Style

Mohammed MEA, Almonawar NAA, Alasmari MFA, Alqarni AA, Algadmi MS, Alshahrani FAM, Alzahrani MS, Almarir AM, Alasiri NA, Alnahdi LK, Alahmari AM, Alshehri AY. Recurrent pregnancy loss and antiphospholipid syndrome: a systematic review of novel autoantibodies and immunological pathways. https://www.ijmdc.com/?mno=305530 [Access: February 23, 2026]. doi:10.24911/IJMDC.51-1767548421

AMA (American Medical Association) Style

Mohammed MEA, Almonawar NAA, Alasmari MFA, Alqarni AA, Algadmi MS, Alshahrani FAM, Alzahrani MS, Almarir AM, Alasiri NA, Alnahdi LK, Alahmari AM, Alshehri AY. Recurrent pregnancy loss and antiphospholipid syndrome: a systematic review of novel autoantibodies and immunological pathways. IJMDC. 2026; 10(3): 1026-1035. doi:10.24911/IJMDC.51-1767548421


Vancouver/ICMJE Style

Mohammed MEA, Almonawar NAA, Alasmari MFA, Alqarni AA, Algadmi MS, Alshahrani FAM, Alzahrani MS, Almarir AM, Alasiri NA, Alnahdi LK, Alahmari AM, Alshehri AY. Recurrent pregnancy loss and antiphospholipid syndrome: a systematic review of novel autoantibodies and immunological pathways. IJMDC. (2026), [cited February 23, 2026]; 10(3): 1026-1035. doi:10.24911/IJMDC.51-1767548421


Harvard Style

Mohammed, . M. E. A., Almonawar, . N. A. A., Alasmari, . M. F. A., Alqarni, . A. A., Algadmi, . M. S., Alshahrani, . F. A. M., Alzahrani, . M. S., Almarir, . A. M., Alasiri, . N. A., Alnahdi, . L. K., Alahmari, . A. M. & Alshehri, . A. Y. (2026) Recurrent pregnancy loss and antiphospholipid syndrome: a systematic review of novel autoantibodies and immunological pathways. IJMDC, 10 (3), 1026-1035. doi:10.24911/IJMDC.51-1767548421


Turabian Style

Mohammed, ‏yousef Mohammed Elamin Ali, Nora Alhussein Ali Almonawar, Mohammed Fareed A Alasmari, Abdulaziz Awad Alqarni, Mohammed Saeed Algadmi, Faisal Ali M. Alshahrani, Maha Saeed Alzahrani, Aisha Mofareh Almarir, Naif Ahmed Alasiri, Lama Khalid Alnahdi, Amal Mohammad Alahmari, and Ali Yahya Alshehri. 2026. Recurrent pregnancy loss and antiphospholipid syndrome: a systematic review of novel autoantibodies and immunological pathways. International Journal of Medicine in Developing Countries, 10 (3), 1026-1035. doi:10.24911/IJMDC.51-1767548421


Chicago Style

Mohammed, ‏yousef Mohammed Elamin Ali, Nora Alhussein Ali Almonawar, Mohammed Fareed A Alasmari, Abdulaziz Awad Alqarni, Mohammed Saeed Algadmi, Faisal Ali M. Alshahrani, Maha Saeed Alzahrani, Aisha Mofareh Almarir, Naif Ahmed Alasiri, Lama Khalid Alnahdi, Amal Mohammad Alahmari, and Ali Yahya Alshehri. "Recurrent pregnancy loss and antiphospholipid syndrome: a systematic review of novel autoantibodies and immunological pathways." International Journal of Medicine in Developing Countries 10 (2026), 1026-1035. doi:10.24911/IJMDC.51-1767548421


MLA (The Modern Language Association) Style

Mohammed, ‏yousef Mohammed Elamin Ali, Nora Alhussein Ali Almonawar, Mohammed Fareed A Alasmari, Abdulaziz Awad Alqarni, Mohammed Saeed Algadmi, Faisal Ali M. Alshahrani, Maha Saeed Alzahrani, Aisha Mofareh Almarir, Naif Ahmed Alasiri, Lama Khalid Alnahdi, Amal Mohammad Alahmari, and Ali Yahya Alshehri. "Recurrent pregnancy loss and antiphospholipid syndrome: a systematic review of novel autoantibodies and immunological pathways." International Journal of Medicine in Developing Countries 10.3 (2026), 1026-1035. Print. doi:10.24911/IJMDC.51-1767548421


APA (American Psychological Association) Style

Mohammed, . M. E. A., Almonawar, . N. A. A., Alasmari, . M. F. A., Alqarni, . A. A., Algadmi, . M. S., Alshahrani, . F. A. M., Alzahrani, . M. S., Almarir, . A. M., Alasiri, . N. A., Alnahdi, . L. K., Alahmari, . A. M. & Alshehri, . A. Y. (2026) Recurrent pregnancy loss and antiphospholipid syndrome: a systematic review of novel autoantibodies and immunological pathways. International Journal of Medicine in Developing Countries, 10 (3), 1026-1035. doi:10.24911/IJMDC.51-1767548421




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