カトウ　タマキ   Katou Tamaki   加藤　環    所属   医学部 医学科（東京女子医科大学病院）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	RAG1 deficiency may present clinically as selective IgA deficiency.
掲載誌名	正式名：Journal of clinical immunology 略　 称：J Clin Immunol ISSNコード：15732592/02719142
掲載区分	国外
巻・号・頁	35(3),pp.280-8
著者・共著者	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
発行年月	2015/04
概要	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