Journal Article

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

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

2025

Overview

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.

• Publisher: Springer US,Springer Nature B.V
• Subject: adaptive immunity / Adolescent / Adult / Ataxia telangiectasia / Biomedical and Life Sciences / Biomedicine / bone marrow / Child / Child, Preschool / Common variable immunodeficiency / Cytokinesis / DNA repair / DNA Repair - genetics / DNA Repair-Deficiency Disorders - genetics / Female / Genetic disorders / Genetic diversity / Genetic variability / Humans / Immune system / Immunity / Immunology / immunosuppression / Infant / Infectious Diseases / Internal Medicine / Lymphocytes / Male / Malignancy / Medical Microbiology / Micronucleus Tests / Middle Aged / Patients / Phenotypes / Radiation / Radiation Tolerance - genetics / Radiosensitivity / therapeutics / Young Adult