{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:07:47Z","timestamp":1788847667983,"version":"build-2803163510"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"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>Background<\/jats:title>\n                    <jats:p>Acquired aplastic anemia (AA) is an immune-mediated bone marrow failure syndrome characterized by destruction of hematopoietic stem and progenitor cells (HSPCs). Although HLA class II alleles are consistently associated with disease susceptibility, the candidate self-peptides presented by these molecules remain largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a retrospective case-control study evaluating HLA class II associations in 35 patients with AA and 570 unrelated healthy controls. Bulk transcriptomic analysis of untreated Lin\n                      <jats:sup>-<\/jats:sup>\n                      CD34\n                      <jats:sup>+<\/jats:sup>\n                      HSPCs (GSE165870) identified differentially expressed genes, which were subsequently prioritized using an independent single-cell RNA sequencing dataset (GSE145668) to identify genes preferentially expressed in HSPCs relative to T cells. Canonical protein sequences were fragmented into overlapping 15-mer peptides and analyzed for binding to disease-associated HLA class II molecules using NetMHCIIpan v4.3j.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HLA-DRB1*15:01, HLA-DQB1*06:02, and HLA-DRB5*01:01 were significantly enriched in patients with AA, and the three-allele co-occurrence pattern showed the strongest association with disease susceptibility. Bulk transcriptomic analysis identified 98 differentially expressed genes, including a prominent interferon-associated transcriptional program. Integration with single-cell transcriptomic data prioritized nine HSPC-enriched genes (SNCA, UHRF1, SH2D3C, SLC25A39, ADIPOR1, BNIP3L, LAT2, MEF2A, and LGALS1) for downstream analyses. NetMHCIIpan identified multiple predicted HLA class II binders across the three disease-associated HLA molecules, with SNCA, UHRF1, SH2D3C, ADIPOR1, and SLC25A39 emerging as the highest-priority candidate proteins based on normalized binding density and predicted binding affinity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This integrative analysis combines HLA genetics, transcriptomics, and computational peptide-binding prediction to prioritize candidate HSPC-derived self-peptides in acquired AA. These findings provide a hypothesis-generating framework for future immunopeptidomic and functional studies aimed at identifying the antigenic targets underlying immune-mediated bone marrow failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1896015","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:35:28Z","timestamp":1788845728000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Linking HLA class II susceptibility to HSPC transcriptomics and antigen presentation in aplastic anemia"],"prefix":"10.3389","volume":"17","author":[{"given":"Maximiliano","family":"Correa Lara","sequence":"first","affiliation":[{"name":"Center for Research and Advanced Studies of the National Polytechnic Institute \u2013 Cinvestav, Molecular Biomedicine","place":["Mexico City, Mexico"]},{"name":"National Medical Center \u201cLa Raza\u201d, Mexican Social Security 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