title: Identification of anti-herpes simplex virus antibody-producing B cells in a patient with an atypical RAG1 immunodeficiency.
abstract: Mutations of the RAG1 or RAG2 protein that eliminate their recombination activity result in T-B-severe combined immunodeficiency (SCID), whereas mutations retaining partial recombination activity lead to Omenn syndrome, a peculiar SCID characterized by increased host T cells and absence of circulating B cells. The prognosis of this disease is fatal, unless hematopoietic stem cell transplantation is performed. This study reports a case of atypical SCID, carrying RAG1 mutations. The patient survived for 6 years without hematopoietic stem cell transplantation. The missense mutation, tested by in vivo recombination assay, revealed residual recombination activity. By the age of 5 years, the patient developed host B cells, but not T cells, possibly due to engrafted maternal T cells. In addition, the host B cells were able to produce antibodies, including anti-herpes simplex virus-antibodies. The fact that host B cells could produce antibodies in this patient could explain not only the mild phenotype observed but also, at least in part, how patients with Omenn syndrome produce immunoglobulin E and sometimes immunoglobulin M, as the same missense mutation of RAG1 gene has been reported in a patient with Omenn syndrome.
authors.affiliation: Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. kumakis@idac.tohoku.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Kumaki
authors.forename: A
authors.initials: A
authors.lastname: Villa
authors.forename: H
authors.initials: H
authors.lastname: Asada
authors.forename: S
authors.initials: S
authors.lastname: Kawai
authors.forename: Y
authors.initials: Y
authors.lastname: Ohashi
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: I
authors.initials: I
authors.lastname: Hakozaki
authors.forename: E
authors.initials: E
authors.lastname: Nitanai
authors.forename: M
authors.initials: M
authors.lastname: Minegishi
authors.forename: S
authors.initials: S
authors.lastname: Tsuchiya
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D004252:DNA Mutational Analysis; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007073:Immunoglobulin E / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007223:Infant; D007239:Infections / Q000209:etiology; D008213:Lymphocyte Activation; D008297:Male; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D011995:Recombination, Genetic; D012008:Recurrence; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology*; D018139:Simplexvirus / Q000276:immunology*; D013577:Syndrome; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D045567:VDJ Recombinases
chemical_list: D000914:Antibodies, Viral; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D007075:Immunoglobulin M; C064658:RAG-1 protein; D007073:Immunoglobulin E; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases