{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T01:49:20Z","timestamp":1790560160988,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,8,8]],"date-time":"2020-08-08T00:00:00Z","timestamp":1596844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by the destruction of platelets in the fetus or newborn by maternal platelet alloantibodies, mostly against human platelet antigen (HPA)\u20101a. Recent studies indicate that two anti\u2010HPA subtypes exist: Type I reacts with epitopes residing on the plexin\u2010semaphorin\u2010integrin (PSI) and type II with plexin\u2010semaphorin\u2010integrin\/integrin epidermal growth factor 1 (I\u2010EGF1) domains of the \u03b23 integrin. Here, we evaluated whether a Cys460Trp mutation in the I\u2010EGF1 domain found in a patient with Glanzmann thrombasthenia can alter the binding of anti\u2010HPA\u20101a.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Stable HEK293 cell lines expressing wild\u2010type and mutant \u03b1IIb\u03b23 and \u03b1v\u03b23 were generated to prove the reactivity of different antibodies against HPA\u20101a.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Flow cytometry analysis of wild\u2010type (Cys460) and mutant (Trp460) expressed on HEK293 cells showed equal surface expression of \u03b1IIb\u03b23 and \u03b1v\u03b23. When tested with mutant \u03b1IIb\u03b23 cells, reduced binding was observed in Type II but not in Type I anti\u2010HPA\u20101a. These results could be confirmed with platelets carrying Cys460Trp mutation. Interestingly, reduced binding of Type I antibodies was detected with mutant \u03b1v\u03b23 cells. Both antibody types were found in maternal sera from FNAIT cases by an antigen\u2010capture assay with use of HEK293 transfected cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These observations confirm the existence of Type I and Type II anti\u2010HPA\u20101a. Furthermore, this study underlines different immunogenicity of HPA\u20101a antigen(s) residing on either \u03b1IIb\u03b23 or \u03b1v\u03b23. Further analysis of FNAIT cases from mothers having a fetus with and without intracranial bleedings with use of such an approach may highlight the functional relevance of different anti\u2010HPA\u20101a subtypes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.15960","type":"journal-article","created":{"date-parts":[[2020,8,8]],"date-time":"2020-08-08T07:10:48Z","timestamp":1596870648000},"page":"2097-2107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Naturally occurring point mutation <scp>Cys460Trp<\/scp> located in the <scp>I\u2010EGF1<\/scp> domain of integrin \u03b23 alters the binding of some <scp>anti\u2010HPA<\/scp>\u2010<scp>1a<\/scp> antibodies"],"prefix":"10.1111","volume":"60","author":[{"given":"Sarah Theresa","family":"Holzwarth","sequence":"first","affiliation":[{"name":"Institute for Clinical Immunology and Transfusion Medicine Justus\u2010Liebig University Giessen  Giessen 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