A variant of SCID with specific immune responses and predominance of gamma delta T cells.
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.
Ehl
Stephan
S
Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany. ehl@kikli.ukl.uni-freiburg.de
Schwarz
Klaus
K
Enders
Anselm
A
Duffner
Ulrich
U
Pannicke
Ulrich
U
Kühr
Joachim
J
Mascart
Françoise
F
Schmitt-Graeff
Annette
A
Niemeyer
Charlotte
C
Fisch
Paul
P
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*
D018398:Homeodomain Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C064658:RAG-1 protein