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All Journal Indonesian Journal of Perinatology
Wibisana Andika Krista Dharma
Undergraduate Program in Medical Science, Faculty of Medicine, Gajah Mada University, Special Region of Yogyakarta, Yogyakarta, Indonesia.
Health Professions Medicine & Pharmacology Nursing

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Systems perinatology of autoimmunity: placental immune endophenotypes linking SLE, RA, Sjögren’s, and APS to specific obstetric complications: a systematic review and translational framework Wisnu Prabowo; I Nyoman Hariyasa Sanjaya; Wiku Andonotopo; Muhammad Adrianes Bachnas; Mochammad Besari Adi Pramono; Julian Dewantiningrum; Efendi Lukas; Anak Agung Gede Putra Wiradnyana; Anak Agung Ngurah Jaya Kusuma; Khanisyah Erza Gumilar; Ernawati Darmawan; Dudy Aldiansyah; Aloysius Suryawan; Ridwan Abdullah Putra; Cut Meurah Yeni; Nuswil Bernolian; Laksmana Adi Krista Nugraha; Waskita Ekamaheswara Kasumba Andanaputra; Wibisana Andika Krista Dharma; Niranjani
Indonesian Journal of Perinatology Vol. 7 No. 1 (2026): Available online: 1 June 2026
Publisher : The Indonesian Society of Perinatology, South Jakarta, Indonesia

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Abstract

Autoimmune diseases—including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome, and antiphospholipid syndrome (APS)—confer disproportionate risk for adverse obstetric outcomes, yet the underlying placental immunopathology remains fragmented across disciplines. This systematic review integrates evidence from 2012–2025 to define reproducible placental immune endophenotypes linking maternal autoimmunity to obstetric complications. Following PRISMA 2020 guidelines, a comprehensive search of PubMed, Embase, and ClinicalTrials.gov identified 1,042 records, of which 54 studies met eligibility after duplicate removal, multi-reviewer screening, and bias appraisal (AMSTAR-2, ROBINS-I, NOS). No protocol was registered on PROSPERO. Evidence was synthesizednarratively and diagrammatically to capture mechanistic convergence across diseases. Findings delineate six immune endophenotype axes—type I interferon, complement/NETosis, B-cell/autoantibody, FcRn–IgG transport, microchimerism, and stromal–immune crosstalk—each associated with specific placental lesions (e.g., villitis, intervillositis, fibrinoid necrosis) and outcomes including preeclampsia, fetal growth restriction, preterm birth, and fetal loss. SLE and APS dominate complement-mediated patterns, whereas RA and Sjögren’s reflect IFN-driven trophoblast stress and stromal immune imbalance. Integrating histopathology, single-cell transcriptomics, and biomarker data, this framework proposes a Systems Perinatology model bridging discovery, mechanism, and clinical translation.This review reconceptualizes autoimmune pregnancy not as disease-specific, but as an endophenotype-mediated placental immune disorder amenable to precision stratification and targeted therapy. Future research should operationalize these axes for biomarker development, interventional trials, and predictive algorithms in precision obstetrics.
Co-Authors Aloysius Suryawan Anak Agung Gede Putra Wiradnyana Anak Agung Ngurah Jaya Kusuma Cut Meurah Yeni Dudy Aldiansyah Efendi Lukas Ernawati Darmawan I Nyoman Hariyasa Sanjaya Julian Dewantiningrum Khanisyah Erza Gumilar Laksmana Adi Krista Nugraha Mochammad Besari Adi Pramono Muhammad Adrianes Bachnas Niranjani Nuswil Bernolian Ridwan Abdullah Putra Waskita Ekamaheswara Kasumba Andanaputra Wiku Andonotopo Wisnu Prabowo