Combined Immunodeficiency With Late-Onset Progressive Hypogammaglobulinemia and Normal B Cell Count in a Patient With RAG2 Deficiency

Frontiers in Pediatrics

article

Mayra B. Dorna¹  Jolan E. Walter²  Pamela F. A. Barbosa¹  Andréia Rangel-Santos⁵  Krisztian Csomos²  Boglarka Ujhazi²  Joseph F. Dasso²  Daniel Thwaites⁷  Joan Boyes⁷  Sinisa Savic⁸ 

[1] Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo;Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, United States;Johns Hopkins All Children's Hospital, United States;Massachusetts General Hospital, United States;Laboratory of Medical Investigation (LIM 36), Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo, Hospital das Clínicas;Department of Biology, University of Tampa, United States;School of Molecular and Cellular Biology, University of Leeds, United Kingdom;Department of Clinical Immunology and Allergy, Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James's University Hospital, United Kingdom

关键词: RAG deficiency;    RAG2;    combined immunodeficiency;    primary immunodeficiency;    hypomorphic variant;    compound heterozygous variant;   

DOI  :  10.3389/fped.2019.00122

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY