Tamaki Kato    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	RAG1 deficiency may present clinically as selective IgA deficiency.
Journal	Formal name：Journal of clinical immunology Abbreviation：J Clin Immunol ISSN code：15732592/02719142
Domestic / Foregin	Foregin
Volume, Issue, Page	35(3),pp.280-8
Author and coauthor	Kato Tamaki, Crestani Elena, Kamae Chikako, Honma Kenichi, Yokosuka Tomoko, Ikegawa Takeshi, Nishida Naonori, Kanegane Hirokazu, Wada Taizo, Yachie Akihiro, Ohara Osamu, Morio Tomohiro, Notarangelo Luigi D, Imai Kohsuke, Nonoyama Shigeaki
Publication date	2015/04
Summary	BACKGROUND:Recombination-activating gene (RAG) 1 and 2 deficiency is seen in patients with severe combined immunodeficiency (SCID) and Omenn syndrome. However, the spectrum of the disease has recently expanded to include a milder phenotype.OBJECTIVE:We analyzed a 4-year-old boy who was initially given the diagnosis of selective immunoglobulin A deficiency (SIgAD) based on immunoglobulin serum levels without any opportunistic infections, rashes, hepatosplenomegaly, autoimmunity or granulomas. The patient was found to be infected with varicella zoster; however, the clinical course was not serious. He produced antiviral antibodies.METHODS:We performed lymphocyte phenotyping, quantification of T cell receptor excision circles (TRECs) and kappa deleting recombination excision circles (KRECs), an analysis of target sequences of RAG1 and 2, a whole-genome SNP array, an in vitro V(D)J recombination assay, a spectratype analysis of the CDR3 region and a flow cytometric analysis of the bone marrow.RESULTS:Lymphocyte phenotyping demonstrated that the ratio of CD4+ to CD8+ T cells was inverted and the majority of CD4+T cells expressed CD45RO antigens in addition to the almost complete lack of B cells. Furthermore, both TRECs and KRECs were absent. Targeted DNA sequencing and SNP array revealed that the patient carried a deletion of RAG1 and RAG2 genes on the paternally-derived chromosome 11, and two maternally-derived novel RAG1 missense mutations (E455K, R764H). In vitro analysis of recombination activity showed that both RAG1 mutant proteins had low, but residual function.CONCLUSIONS:The current case further expands the phenotypic spectrum of mild presentations of RAG deficiency, and suggests that TRECs and KRECs are useful markers for detecting hidden severe, as well as mild, cases.
DOI	10.1007/s10875-015-0146-4
PMID	25739914