{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:02:12Z","timestamp":1785391332860,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"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>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Platelet transfusion refractoriness (PTR) is a common and clinically challenging condition with complex underlying mechanisms. Human leukocyte antigen (HLA) alloimmunization is the principal cause of immune PTR (iPTR), whereas non-HLA antibodies (non-HLA Abs) are known to contribute to antibody-mediated rejection, microvascular inflammation, interstitial fibrosis, and graft loss. However, whether non-HLA Abs contribute to the development of PTR and how they are associated with HLA alloimmunization remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective study evaluated the expression profiles of 60 non-HLA Abs and the degree of HLA alloimmunization in 32 patients with PTR and 20 healthy blood donors using a multiplex Luminex single-antigen bead assay.\n                      <jats:italic>GSTT1<\/jats:italic>\n                      gene deletion status in this cohort was determined by quantitative PCR (qPCR). Risk factors associated with the development of non-HLA Abs in PTR patients were analyzed using multivariable logistic regression with penalized maximum likelihood estimation (Firth correction).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The overall positivity rate of non-HLA Abs in PTR patients was significantly higher than that in healthy blood donors (90.63% vs. 55%,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.006). Among the 14 positive non-HLA Abs tested, none showed statistically significant differences in odds ratios (ORs) between the non-iPTR and iPTR groups. Compared with healthy donors, only the positivity rates of CSF2 Ab and GSTT1 Ab were significantly increased in the non-iPTR and\/or iPTR groups. A history of multiple transfusions was strongly associated with overall non-HLA Ab positivity, as well as with CSF2 Ab and GSTT1 Ab positivity (OR\u00a0=\u00a06.12,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.008; OR\u00a0=\u00a021.9,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.001; OR\u00a0=\u00a012.56,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.017). Overall, 26 of 52 individuals (50%) across all groups exhibited homozygous deletion of the GSTT1 gene (\n                      <jats:italic>GSTT1<\/jats:italic>\n                      *0\/0), among whom 34.62% (9\/26) developed GSTT1 Ab. Among PTR patients with\n                      <jats:italic>GSTT1<\/jats:italic>\n                      *0\/0, 56.25% (9\/16) were positive for GSTT1 Ab. In contrast, no GSTT1 Ab were detected in healthy donors, although 45% (9\/20) had a history of pregnancy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In this exploratory pilot study, non-HLA antibody profiles were independently correlated with PTR beyond HLA sensitization, with multiple transfusions as a clinically relevant factor linked to CSF2 and GSTT1 Abs, whereas the\n                      <jats:italic>GSTT1*0\/0<\/jats:italic>\n                      genotype appeared to be a prerequisite for the formation of GSTT1 Abs. Whether incorporating non-HLA antibody screening and GSTT1 genotyping into pre-transfusion evaluation can improve precision transfusion remains to be validated in prospective studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1886771","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:39:55Z","timestamp":1785389995000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond HLA: an exploratory pilot study of non-HLA antibodies, HLA sensitization, and GSTT1 genotype in platelet transfusion refractoriness"],"prefix":"10.3389","volume":"17","author":[{"given":"Jun","family":"Qi","sequence":"first","affiliation":[{"name":"HLA Laboratory, Shaanxi Province Blood Center, Institute of Xi\u2019an Blood Bank","place":["Xi\u2019an, Shaanxi, 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Institute of Xi\u2019an Blood Bank","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaofeng","family":"Ma","sequence":"additional","affiliation":[{"name":"HLA Laboratory, Shaanxi Province Blood Center, Institute of Xi\u2019an Blood Bank","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Xu","sequence":"additional","affiliation":[{"name":"HLA Laboratory, Shaanxi Province Blood Center, Institute of Xi\u2019an Blood Bank","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2020.09.010","article-title":"Human leukocyte antigen alloimmunization and alloimmune platelet refractoriness","volume":"34","author":"Saris","year":"2020","journal-title":"Transfus Med 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