{"id":47455,"date":"2025-11-04T12:00:00","date_gmt":"2025-11-04T11:00:00","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/11\/04\/overrepresentation-of-germline-immune-related-gene-variants-in-patients-with-acquired-bone-marrow-failure\/"},"modified":"2025-11-04T12:00:00","modified_gmt":"2025-11-04T11:00:00","slug":"overrepresentation-of-germline-immune-related-gene-variants-in-patients-with-acquired-bone-marrow-failure","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/11\/04\/overrepresentation-of-germline-immune-related-gene-variants-in-patients-with-acquired-bone-marrow-failure\/","title":{"rendered":"Overrepresentation of Germline Immune-Related Gene Variants in Patients with Acquired Bone Marrow Failure"},"content":{"rendered":"
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J Clin Immunol<\/b>. 2025 Nov 5;45(1):150. doi: 10.1007\/s10875-025-01951-6.<\/p>\n

ABSTRACT<\/b><\/p>\n

PURPOSE: Bone marrow failure (BMF) in idiopathic aplastic anemia (AA) and hypoplastic myelodysplastic neoplasms (MDS-h) results from the destruction of hematopoietic progenitors by autoreactive T cells; however, the molecular events driving the pathogenesis of these disorders remain unclear. We therefore applied whole-exome sequencing (WES) in AA and MDS-h patients to identify acquired and inherited gene variants presumed to have functional consequences for BMF. We also used transcriptome profiling to investigate the molecular mechanisms underlying the aberrant T cell response.<\/p>\n

METHODS: WES was performed on DNA from 42 patients at diagnosis. Transcriptome profiling of CD3\u207a cells was conducted in 21 patients and 10 healthy donors. Peripheral blood cell populations were analyzed by flow cytometry.<\/p>\n

RESULTS: Pathogenic\/likely pathogenic (P\/LP) somatic gene variants were detected in 79% of patients and were functionally associated with BMF-relevant processes such as antigen processing\/presentation, T cell-mediated immunity, and DNA repair. P\/LP germline gene variants were found in all patients, almost half of whom harbored variants associated with inborn errors of immunity. Patient T cells displayed expression signatures of increased inflammation, apoptosis, hypoxia response, and decreased oxidative phosphorylation. Dysregulated long noncoding RNAs were predicted to primarily regulate the differentiation of T helper 17 cells. Patients also showed significantly lower frequencies of immature progenitors and natural killer cells compared with controls.<\/p>\n

CONCLUSION: Patients with idiopathic AA and MDS-h carried multiple germline immune-related gene variants that may increase susceptibility to immune-mediated BMF. Furthermore, patient T cells exhibited altered energy metabolism, which may represent a therapeutic target for modulating immune responses in autoimmune diseases.<\/p>\n

PMID:41188636<\/a> | DOI:10.1007\/s10875-025-01951-6<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

J Clin Immunol. 2025 Nov 5;45(1):150. doi: 10.1007\/s10875-025-01951-6. ABSTRACT PURPOSE: Bone marrow failure (BMF) in idiopathic aplastic anemia (AA) and hypoplastic myelodysplastic neoplasms (MDS-h) results from the destruction of hematopoietic progenitors by autoreactive T cells; however, the molecular events driving the pathogenesis of these disorders remain unclear. We therefore applied whole-exome sequencing (WES) in AA … Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[69,42],"tags":[],"class_list":["post-47455","post","type-post","status-publish","format-standard","hentry","category-journal-of-clinical-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/47455","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=47455"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/47455\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=47455"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=47455"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=47455"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}