Beyls Elien, Duthoo Evi, Backers Lynn, Claes Karlien, De Bruyne Marieke, Pottie Lore, Bordon Victoria, Bonroy Carolien, Tavernier Simon J, Claes Kathleen B M, Vral Anne, Baeyens Ans, Haerynck Filomeen
Primary Immunodeficiency Research Lab (PIRL), Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
Center for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Center, Ghent University Hospital, Ghent, Belgium.
J Clin Immunol. 2025 Feb 13;45(1):75. doi: 10.1007/s10875-025-01858-2.
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.
人类遗传性免疫缺陷（IEI）是一组影响先天性和/或适应性免疫系统的多种遗传性疾病。一些IEI实体包括DNA修复因子缺陷，导致（严重）联合免疫缺陷、骨髓衰竭、易患恶性肿瘤，并可能导致放射敏感性（RS）。虽然其他IEI亚类，如常见变异免疫缺陷（CVID）和免疫失调疾病也与淋巴增殖性和恶性并发症相关，但在更广泛的IEI人群中RS表型的发生情况尚未得到充分表征。尽管如此，通过功能测试在IEI患者中识别RS对于重新考虑与放射相关的治疗方案和改善患者整体管理至关重要。本研究旨在使用G0期胞质分裂阻滞微核（MN）试验，对107名IEI患者的不同队列进行染色体RS研究。我们的研究结果表明，特定遗传和表型亚组之间的RS存在显著差异。在所有共济失调毛细血管扩张症（AT）患者、一名FANCI缺陷和ERCC6L2缺陷患者中检测到严重RS，但在该队列中的任何其他IEI患者中均未检测到。年龄是自发和辐射诱导MN产量的影响因素，而包括感染易感性、免疫失调或恶性肿瘤在内的其他临床特征的表现与MN水平升高无关。我们对IEI人群中RS的广泛分析强调了在AT患者中进行RS评估的临床重要性，并支持对所有怀疑患有与RS相关的DNA修复障碍的IEI患者进行RS检测。
