Dorna Mayra B, Barbosa Pamela F A, Rangel-Santos Andréia, Csomos Krisztian, Ujhazi Boglarka, Dasso Joseph F, Thwaites Daniel, Boyes Joan, Savic Sinisa, Walter Jolan E
Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Laboratory of Medical Investigation (LIM 36), Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo, Hospital das Clínicas, São Paulo, Brazil.
Front Pediatr. 2019 Apr 16;7:122. doi: 10.3389/fped.2019.00122. eCollection 2019.
Proteins expressed by recombination activating genes 1 and 2 (RAG1/2) are essential in the process of V(D)J recombination that leads to generation of the T and B cell repertoires. Clinical and immunological phenotypes of patients with RAG deficiencies correlate well to the degree of impaired RAG activity and this has been expanding to variants of combined immunodeficiency (CID) or even milder antibody deficiency syndromes. Pathogenic variants that severely impair recombinase activity of RAG1/2 determine a severe combined immunodeficiency (SCID) phenotype, whereas hypomorphic variants result in leaky (partial) SCID and other immunodeficiencies. We report a patient with novel pathogenic compound heterozygous variants that result in a CID phenotype with two distinctive characteristics: late-onset progressive hypogammaglobulinemia and highly elevated B cell count. In addition, the patient had early onset of infections, T cell lymphopenia and expansion of lymphocytes after exposure to herpes family viruses. This case highlights the importance of considering pathogenic RAG variants among patients with preserved B cell count and CID phenotype.
重组激活基因1和2（RAG1/2）所表达的蛋白质在V（D）J重组过程中至关重要，该过程导致T和B细胞库的产生。RAG缺陷患者的临床和免疫表型与RAG活性受损程度密切相关，这已扩展到联合免疫缺陷（CID）的变体甚至更轻微的抗体缺陷综合征。严重损害RAG1/2重组酶活性的致病变异决定了严重联合免疫缺陷（SCID）表型，而亚效变异则导致渗漏性（部分）SCID和其他免疫缺陷。我们报告了一名患有新型致病性复合杂合变异的患者，该变异导致CID表型具有两个独特特征：迟发性进行性低丙种球蛋白血症和B细胞计数高度升高。此外，该患者感染早发、T细胞淋巴细胞减少且在接触疱疹病毒家族病毒后淋巴细胞扩增。该病例突出了在B细胞计数正常且具有CID表型的患者中考虑致病性RAG变异的重要性。
