Combined Immunodeficiency With Late-Onset Progressive Hypogammaglobulinemia and Normal B Cell Count in a Patient With RAG2 Deficiency
Combined Immunodeficiency With Late-Onset Progressive Hypogammaglobulinemia and Normal B Cell Count in a Patient With RAG2 Deficiency
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DOI：
10.3389/fped.2019.00122
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发表时间：
2019-04-16
影响因子：
2.6
通讯作者：
Walter, Jolan E.
中科院分区：
文献类型：
--
作者：
Dorna, Mayra B.;Barbosa, Pamela F. A.;Walter, Jolan E.
由重组激活基因1和2（RAG 1/2）表达的蛋白质在导致T和B细胞库产生的V（D）J重组过程中是必需的。RAG缺陷患者的临床和免疫学表型与RAG活性受损的程度密切相关，这已经扩展到联合免疫缺陷（CID）的变体或甚至更温和的抗体缺陷综合征。严重损害RAG 1/2重组酶活性的致病性变体决定了严重的联合免疫缺陷（SCID）表型，而亚型变体导致渗漏（部分）SCID和其他免疫缺陷。我们报告了一个新的致病性复合杂合RAG 2变异，导致CID表型有两个独特的特点：迟发性进行性低丙种球蛋白血症和高度升高的B细胞计数的患者。此外，患者在接触疱疹家族病毒后出现早期感染、T细胞淋巴细胞减少和淋巴细胞扩张。该病例强调了在保留B细胞计数和CID表型的患者中考虑致病性RAG变异的重要性。
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 RAG2 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.