Boz Valentina, Tesser Alessandra, Girardelli Martina, Burlo Francesca, Pin Alessia, Severini Giovanni Maria, De Marchi Ginevra, Verzegnassi Federico, Naviglio Samuele, Tommasini Alberto, Valencic Erica
Department of Pediatrics, Institute for Maternal and Child Health IRCCS Burlo Garofolo, Via dell'Istria 65, 34137 Trieste, Italy.
Department of Medical, Surgical and Health Sciences, University of Trieste, 34137 Trieste, Italy.
Biomedicines. 2023 Apr 27;11(5):1299. doi: 10.3390/biomedicines11051299.
Inborn errors of immunity (IEI) associated with immune dysregulation are not sufficiently addressed in shared recommendation, resulting in delayed diagnosis and high morbidity. The availability of precision medicine for some of these immune defects makes it urgent to evaluate effective strategies to diagnose and treat such defects before the occurrence of severe complications. A diagnosis of an IEI in these patients enabled the use of a more specific treatment in most cases, and these have the potential to prevent further disease progression. We studied immune dysregulation diseases in 30 patients with autoimmune or allergic phenotypes, exploiting data from clinics and immunophenotype, genetic and transcriptome investigations, and 6 of them were diagnosed with a monogenic disorder. Our results confirm that a non-negligible number of children with IEIs may present with signs and symptoms of immune dysregulation and share many features with common multifactorial immune conditions. Reaching a genetic diagnosis becomes more likely in the presence of multiple clinical manifestations, especially when in association with abnormalities of lymphocytes subsets and/or immunoglobulins levels. Moreover, 5 of 6 patients that obtained a diagnosis of monogenic disorder received precision therapy, in four cases with a good or moderate response.
与免疫失调相关的先天性免疫缺陷（IEI）在共享建议中未得到充分关注，导致诊断延迟和高发病率。针对其中一些免疫缺陷的精准医学的出现，使得在严重并发症发生之前评估诊断和治疗此类缺陷的有效策略变得紧迫。对这些患者进行IEI诊断后，在大多数情况下能够采用更具针对性的治疗方法，并且这些方法有可能预防疾病的进一步进展。我们利用临床数据、免疫表型、基因和转录组研究，对30例具有自身免疫或过敏表型的患者的免疫失调疾病进行了研究，其中6例被诊断为单基因疾病。我们的结果证实，相当数量的患有IEI的儿童可能会出现免疫失调的体征和症状，并且与常见的多因素免疫疾病有许多共同特征。当存在多种临床表现时，尤其是与淋巴细胞亚群和/或免疫球蛋白水平异常相关时，更有可能达成基因诊断。此外，6例被诊断为单基因疾病的患者中有5例接受了精准治疗，4例有良好或中等反应。
