Di Filippo Michela, Tallone Ramona, Muraca Monica, Pelanconi Lisa, Faravelli Francesca, Capra Valeria, De Marco Patrizia, Ognibene Marzia, Baldassari Simona, Terranova Paola, Livellara Virginia, Vellone Valerio Gaetano, Miano Maurizio, Amoroso Loredana, Beccaria Andrea
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal-Infantile Sciences, University of Genoa, 16147 Genoa, Italy.
D.O.P.O. Clinic, Department of Pediatric Hematology and Oncology, IRCCS Giannina Gaslini Institute, 16147 Genoa, Italy.
Int J Mol Sci. 2024 Dec 7;25(23):13181. doi: 10.3390/ijms252313181.
Immune dysregulation in Inborn Errors of Immunity (IEI) shows a broad phenotype, including autoimmune disorders, benign lymphoproliferation, and malignancies, driven by an increasing number of implicated genes. Recent findings suggest that childhood cancer survivors (CCSs) may exhibit immunological abnormalities potentially linked to an underlying IEI, along with a well-known increased risk of subsequent malignancies due to prior cancer treatments. We describe a patient with two composite heterozygous pathogenic variants in the interleukin-2-inducible T-cell kinase () gene and a history of multiple tumors, including recurrent Epstein-Barr virus (EBV)-related nodular sclerosis and Hodgkin's lymphoma (NSHL), associated with unresponsive multiple hand warts, immune thrombocytopenia, and an impaired immunological profile (CD4+ lymphocytopenia, memory B-cell deficiency, reduction in regulatory T-cells, and B-cell- and T-cell-activated profiles). In our case, -related immune dysregulation and prior exposure to oncological treatments seem to have simultaneously intervened in the same individual, leading to the development of a unique clinical profile. It is essential to raise awareness of the two-way association between immune dysregulation disorders and multiple tumors.
免疫缺陷病(IEI)中的免疫失调表现出广泛的表型,包括自身免疫性疾病、良性淋巴细胞增殖和恶性肿瘤,这是由越来越多的相关基因驱动的。最近的研究结果表明,儿童癌症幸存者(CCS)可能表现出潜在与潜在IEI相关的免疫异常,以及由于先前的癌症治疗而导致的后续恶性肿瘤风险增加这一众所周知的情况。我们描述了一名患者,其白细胞介素-2诱导型T细胞激酶()基因存在两个复合杂合致病性变异,并有多种肿瘤病史,包括复发性爱泼斯坦-巴尔病毒(EBV)相关的结节性硬化型霍奇金淋巴瘤(NSHL),同时伴有多发性手部疣无反应、免疫性血小板减少症以及免疫谱受损(CD4+淋巴细胞减少、记忆B细胞缺乏、调节性T细胞减少以及B细胞和T细胞激活谱降低)。在我们的病例中,与相关的免疫失调和先前的肿瘤治疗似乎同时作用于同一个体,导致了独特的临床特征的出现。提高对免疫失调疾病和多种肿瘤之间双向关联的认识至关重要。