High maternal-fetal HLA eplet compatibility is associated with severe manifestation of preeclampsia

• DOI: 10.3389/fimmu.2023.1272021
• Publication Date: 2023-11-03T10:14:32Z
• Authors: Katarzyna Stefańska; Małgorzata Kurkowiak; Karolina Piekarska; Elżbieta Chruściel; Dorota Zamkowska; Joanna Jassem-Bob...; Przemysław Adamski; Renata Świątkowsk...; Anna Abacjew-Chmyłko; Katarzyna Leszczy...; Maciej Zieliński; Krzysztof Preis; Hanna Zielińska; Bogusław Tymoniuk; Piotr Trzonkowski; Natalia Maria Mar...
• Keywords: HLA eplet mismatch load; Immunology; maternal-fetal HLA compatibility; HLA-C Antigens; Hypertension, Pregnancy-Induced; RC581-607; 3. Good health; preeclampsia; Fetus; Pre-Eclampsia; Pregnancy; HLA Antigens; HLA-B Antigens; maternal-fetal immune tolerance; gestational hypertension; Humans; immunology of pregnancy; Female; Immunologic diseases. Allergy; Child

Preeclampsia is responsible for more than 70 000 and 500 maternal fetal deaths, respectively each year. Incomplete remodelling of the spiral arteries in placenta most accepted theory preeclampsia pathogenesis. However, process complexed with immunological background, as pregnancy resembles allograft transplantation. Fetus expresses human leukocyte antigens (HLA) inherited from both parents, thus semiallogeneic to immune system. Therefore, induction tolerance crucial physiological outcome pregnancy. Noteworthy, immunogenicity discordant HLA determined by functional epitopes called eplets, which are continuous discontinuous short sequences amino acids. This way various molecules may express same eplet some incompatibilities can be immunogenic due different combination. we hypothesized that maternal- incompatibility involved pathogenesis gestational hypertension its progression preeclampsia. We also aimed test if particular maternal-fetal mismatches prone anti- antibodies High resolution next-generation sequencing HLA-A, -B, -C, -DQB1 -DRB1 was performed mothers children pregnancies (12 pairs) complicated (22 (27 pairs). In next step identification analysis silico approach HLAMatchmaker algorithm. Simultaneously sera were screened anti-fetal class I, II anti-MICA Luminex, data analyzed HLA-Fusion software. observed high HLA-C, DQB1 compatibility associated severe (PE) manifestation. Both quantity quality epletmismatches affected severity PE. Mismatches HLA-B eplets: 65QIA+76ESN, 70IAO, 180E, HLA-C 193PL3, 267QE, HLA-DRB1 eplet: 16Y a mild complication occurred. HLA-DQB1 between mother child manifestation affects