Investigating Chromosomal Radiosensitivity in Inborn Errors of Immunity: Insights from DNA Repair Disorders and Beyond.

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Tác giả: Lynn Backers, Ans Baeyens, Elien Beyls, Carolien Bonroy, Victoria Bordon, Karlien Claes, Kathleen B M Claes, Marieke De Bruyne, Evi Duthoo, Filomeen Haerynck, Lore Pottie, Simon J Tavernier, Anne Vral

Ngôn ngữ: eng

Ký hiệu phân loại: 912.01 Philosophy and theory

Thông tin xuất bản: Netherlands : Journal of clinical immunology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 81319

Human inborn errors of immunity (IEI) represent a diverse group of genetic disorders affecting the innate and/or adaptive immune system. Some IEI entities comprise defects in DNA repair factors, resulting in (severe) combined immunodeficiencies, bone marrow failure, predisposition to malignancies, and potentially resulting in radiosensitivity (RS). While other IEI subcategories such as common variable immunodeficiency (CVID) and immune dysregulation disorders also associate with lymphoproliferative and malignant complications, the occurrence of RS phenotypes in the broader IEI population is not well characterized. Nonetheless, identifying RS in IEI patients through functional testing is crucial to reconsider radiation-related therapeutic protocols and to improve overall patient management. This study aimed to investigate chromosomal RS in a diverse cohort of 107 IEI patients using the G0 cytokinesis-block micronucleus (MN) assay. Our findings indicate significant variability in RS across specific genetic and phenotypical subgroups. Severe RS was detected in all ataxia-telangiectasia (AT) patients, a FANCI deficient and ERCC6L2 deficient patient, but not in any other IEI patient included in this cohort. Age emerged as an influencing factor for both spontaneous and radiation-induced MN yields, while the manifestation of additional clinical features, including infection susceptibility, immune dysregulation, or malignancies did not associate with increased MN levels. Our extensive analysis of RS in the IEI population underscores the clinical importance of RS assessment in AT patients and supports RS testing in all IEI patients suspected of having a DNA repair disorder associated with RS.
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