{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T19:57:32Z","timestamp":1784923052678,"version":"3.55.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>In fetal and neonatal alloimmune thrombocytopenia (FNAIT), maternal antibodies react with alloantigen expressed on fetal platelets, leading to their clearance <jats:italic>via<\/jats:italic> antibody-dependent phagocytosis. In Caucasians, most FNAIT cases are caused by anti-HPA-1a antibodies. In contrast, anti-HLA class I antibodies are rarely found in FNAIT, but are frequently implicated in cases of platelet transfusion refractoriness (PTR). This phenomenon leads to ongoing debate regarding the role of anti-HLA class I antibodies in FNAIT. In this study, we investigated the platelet clearance mediated by anti-HLA class I antibodies in whole blood both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clearance of opsonized platelet was analyzed by platelet phagocytosis assay and by antibody administration to Balb\/c female mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>To mimic FNAIT conditions, whole blood was pretreated with anti-HLA antibodies before the phagocytosis of anti-HPA-1a antibody-opsonized platelets. Compared to untreated whole blood, anti-HLA-ABC and anti-HLA-DR IgG antibodies inhibited the phagocytosis of anti-HPA-1a-antibody-opsonized platelets. Similar results were obtained with purified monocytes, indicating that anti-HLA-ABC antibodies bound to monocytes can interfere with antibody-mediated platelet phagocytosis. Furthermore, the administration of anti-MHC-I antibodies to mice led to a significant decrease in the platelet count within 24 h. However, anti-\u03b1IIb\u03b23 antibody administration resulted in significantly higher platelet clearance over different time points. Analysis of antibody-bound platelets showed the presence of anti-\u03b1IIb\u03b23 antibodies on the platelet surface, but not on monocytes. In contrast, anti-MHC-I antibodies were found on both platelets and monocytes. Interestingly, monocytes exhibited higher levels of anti-MHC-I binding than platelets (87.0% vs. 25.5%), most likely because platelets express significantly fewer HLA class I antigens than monocytes, as indicated by our flow cytometric analysis of whole blood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results indicated that anti-MHC-I antibodies preferentially bind to monocytes rather than platelets in whole blood and can be cleared by monocytes <jats:italic>via<\/jats:italic> endocytosis. Furthermore, we found that the presence of anti-HLA class I antibodies did not significantly influence platelet clearance induced by anti-\u03b1IIb\u03b23 antibodies. The question of whether these observations can explain the controversial opinions regarding the relative roles of anti-HLA class I and anti-\u03b1IIb\u03b23 antibodies in FNAIT requires further assessment in a murine model of FNAIT.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1652134","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T04:11:38Z","timestamp":1759464698000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Anti-HLA antibodies bound to monocytes altered antibody-mediated platelet phagocytosis and led to mild 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