title: Multiple reversions of an IL2RG mutation restore T cell function in an X-linked severe combined immunodeficiency patient.
abstract: Reversion mosaicism is increasingly being reported in primary immunodeficiency diseases, but there have been few cases with clinically improved immune function. Here, a case is reported of X-linked severe combined immunodeficiency (SCID-X1) with multiple somatic reversions in T cells, which restored sufficient cell-mediated immunity to overcome viral infection. Lineage-specific analysis revealed multiple reversions in T cell receptor (TCR) αβ+ and TCRγδ+ T cells. Diversity of the TCRVβ repertoire was comparable to normal and, furthermore, mitogen-induced proliferation of the patient's T cells was minimally impaired compared to healthy controls. In vivo and in vitro varicella antigen-specific T cell responses were comparable to those of healthy controls, although a reduced level of T cell receptor excision circles suggested that recent thymic output was low. During long-term evaluation of the patient's immunologic status, both the number of CD4+ and CD8+ T cells and T cell proliferation responses were stable and the patient remained healthy. This case demonstrates that multiple but restricted somatic reversions in T cell progenitors can improve the clinical phenotype of SCID-X1.
authors.affiliation: Department of Pediatrics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. tom0818@kuhp.kyoto-u.ac.jp
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kawai
authors.forename: Megumu
authors.initials: M
authors.lastname: Saito
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishikomori
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasumi
authors.forename: Kazushi
authors.initials: K
authors.lastname: Izawa
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Murakami
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Okamoto
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mori
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakagawa
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Imai
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.forename: Taizo
authors.initials: T
authors.lastname: Wada
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ohmori
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002648:Child; D006801:Humans; D007111:Immunity, Cellular; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics*; D008213:Lymphocyte Activation; D008297:Male; D009154:Mutation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D053632:X-Linked Combined Immunodeficiency Diseases / Q000235:genetics* / Q000276:immunology*
chemical_list: C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta