title: A variant of SCID with specific immune responses and predominance of gamma delta T cells.
abstract: We describe here a patient with a clinical and molecular diagnosis of recombinase activating gene 1-deficient (RAG1-deficient) SCID, who produced specific antibodies despite minimal B cell numbers. Memory B cells were detected and antibodies were produced not only against some vaccines and infections, but also against autoantigens. The patient had severely reduced levels of oligoclonal T cells expressing the alphabeta TCR but surprisingly normal numbers of T cells expressing the gammadelta TCR. Analysis at a clonal level and TCR complementarity-determining region-3 spectratyping for gammadelta T cells revealed a diversified oligoclonal repertoire with predominance of cells expressing a gamma4-delta3 TCR. Several gammadelta T cell clones displayed reactivity against CMV-infected cells. These observations are compatible with 2 non-mutually exclusive explanations for the gammadelta T cell predominance: a developmental advantage and infection-triggered, antigen-driven peripheral expansion. The patient carried the homozygous hypomorphic R561H RAG1 mutation leading to reduced V(D)J recombination but lacked all clinical features characteristic of Omenn syndrome. This report describes a new phenotype of RAG deficiency and shows that the ability to form specific antibodies does not exclude the diagnosis of SCID.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany. ehl@kikli.ukl.uni-freiburg.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehl
authors.forename: Klaus
authors.initials: K
authors.lastname: Schwarz
authors.forename: Anselm
authors.initials: A
authors.lastname: Enders
authors.forename: Ulrich
authors.initials: U
authors.lastname: Duffner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pannicke
authors.forename: Joachim
authors.initials: J
authors.lastname: Kühr
authors.forename: Françoise
authors.initials: F
authors.lastname: Mascart
authors.forename: Annette
authors.initials: A
authors.lastname: Schmitt-Graeff
authors.forename: Charlotte
authors.initials: C
authors.lastname: Niemeyer
authors.forename: Paul
authors.initials: P
authors.lastname: Fisch
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D002999:Clone Cells; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008969:Molecular Sequence Data; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C064658:RAG-1 protein