AIRE deficiency in thymus of 2 patients with Omenn syndrome
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《神经病学神经外科学杂志》
1Istituto di Medicina Molecolare "Angelo Nocivelli," Clinica Pediatrica, and
2Cattedra di Anatomia Patologica, University of Brescia, Brescia, Italy.
3Laboratory of Molecular Immunology and Diabetes, School of Medicine, Kyushu University, Fukuoka, Japan.
4Institute of Immunology, University Hospital Motol, Prague, Czech Republic.
5Istituto Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, Milan, Italy.
6INSERM U429, Necker–Enfants Malades, Paris, France.
Abstract
Omenn syndrome is a severe primary immunodeficiency with putative autoimmune manifestations of the skin and gastrointestinal tract. The disease is caused by hypomorphic mutations in recombination-activating genes that impair but do not abolish the process of VDJ recombination, leading to the generation of autoreactive T cells with a highly restricted receptor repertoire. Loss of central tolerance in genetically determined autoimmune diseases, e.g., autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, is associated with defective expression by medullary thymic epithelial cells of AIRE, the transcription activator that induces thymic expression of tissue-specific antigens. Analysis of AIRE expression in the thymi of 2 Omenn syndrome patients and 1 SCID patient, by real-time RT-PCR and immunohistochemistry, demonstrated a
2Cattedra di Anatomia Patologica, University of Brescia, Brescia, Italy.
3Laboratory of Molecular Immunology and Diabetes, School of Medicine, Kyushu University, Fukuoka, Japan.
4Institute of Immunology, University Hospital Motol, Prague, Czech Republic.
5Istituto Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, Milan, Italy.
6INSERM U429, Necker–Enfants Malades, Paris, France.
Abstract
Omenn syndrome is a severe primary immunodeficiency with putative autoimmune manifestations of the skin and gastrointestinal tract. The disease is caused by hypomorphic mutations in recombination-activating genes that impair but do not abolish the process of VDJ recombination, leading to the generation of autoreactive T cells with a highly restricted receptor repertoire. Loss of central tolerance in genetically determined autoimmune diseases, e.g., autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, is associated with defective expression by medullary thymic epithelial cells of AIRE, the transcription activator that induces thymic expression of tissue-specific antigens. Analysis of AIRE expression in the thymi of 2 Omenn syndrome patients and 1 SCID patient, by real-time RT-PCR and immunohistochemistry, demonstrated a