A variant of SCID with specific immune responses and predominance of T cells
Autor: | Anselm Enders, Klaus Schwarz, Ulrich Duffner, Annette Schmitt-Graeff, Paul Fisch, Joachim Kühr, Charlotte M. Niemeyer, Stephan Ehl, Ulrich Pannicke, Françoise Mascart |
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Rok vydání: | 2005 |
Předmět: |
T-Lymphocytes
T cell Molecular Sequence Data Cytomegalovirus chemical and pharmacologic phenomena Biology Recombination-activating gene Immunophenotyping Immune system medicine Humans Amino Acid Sequence Cells Cultured B cell Homeodomain Proteins Severe combined immunodeficiency Base Sequence T-cell receptor Infant Receptors Antigen T-Cell gamma-delta hemic and immune systems General Medicine Fibroblasts medicine.disease Omenn syndrome Clone Cells medicine.anatomical_structure Cytomegalovirus Infections Immunology Female Severe Combined Immunodeficiency Research Article |
Zdroj: | Journal of Clinical Investigation. 115:3140-3148 |
ISSN: | 0021-9738 |
Popis: | 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. |
Databáze: | OpenAIRE |
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