Overrepresentation of Germline Immune-Related Gene Variants in Patients with Acquired Bone Marrow Failure
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00669806%3A_____%2F25%3A10505058" target="_blank" >RIV/00669806:_____/25:10505058 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/25:10505058 RIV/00216208:11310/25:10505058 RIV/00064165:_____/25:10505058
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OecUoi5Xkq" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OecUoi5Xkq</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s10875-025-01951-6" target="_blank" >10.1007/s10875-025-01951-6</a>
Alternative languages
Result language
angličtina
Original language name
Overrepresentation of Germline Immune-Related Gene Variants in Patients with Acquired Bone Marrow Failure
Original language description
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. METHODS: WES was performed on DNA from 42 patients at diagnosis. Transcriptome profiling of CD3+ cells was conducted in 21 patients and 10 healthy donors. Peripheral blood cell populations were analyzed by flow cytometry. 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. 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
<a href="/en/project/LM2023033" target="_blank" >LM2023033: Czech biobank network</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Clinical Immunology
ISSN
0271-9142
e-ISSN
1573-2592
Volume of the periodical
45
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
150
UT code for WoS article
001608454500002
EID of the result in the Scopus database
2-s2.0-105020894455