<![CDATA[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.]]>
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