title: Selective clinical and immune response of the oligoclonal autoreactive T cells in Omenn patients after cyclosporin A treatment.
abstract: The immunological hallmark of Omenn syndrome (OS) is the expansion and activation of an oligoclonal population of autoreactive T cells. These cells should be controlled rapidly by immunosuppressive agents, such as cyclosporin A (CsA), to avoid tissue infiltration and to improve the general outcome of the patients. Here we studied the clinical and the immune response to CsA in two Omenn patients and also examined the gene expression profile associated with good clinical response to such therapy. T cell receptor diversity was studied in cells obtained from OS patients during CsA therapy. Characterization of gene expression in these cells was carried out by using the TaqMan low-density array. One patient showed complete resolution of his symptoms after CsA therapy. The other patient showed selective response of his oligoclonal T cell population and combination therapy was required to control his symptoms. Transcriptional profile associated with good clinical response to CsA therapy revealed significant changes in 26·6% of the tested genes when compared with the transcriptional profile of the cells before treatment. Different clinical response to CsA in two OS patients is correlated with their immunological response. Varying clonal expansions in OS patients can cause autoimmune features and can respond differently to immunosuppressive therapy; therefore, additional treatment is sometimes indicated. CsA for OS patients causes regulation of genes that are involved closely with self-tolerance and autoimmunity.
authors.affiliation: Cancer Research Center, Edmond and Lily Safra Children's Hospital, Tel Hashomer, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Lev
authors.forename: A J
authors.initials: AJ
authors.lastname: Simon
authors.forename: N
authors.initials: N
authors.lastname: Amariglio
authors.forename: G
authors.initials: G
authors.lastname: Rechavi
authors.forename: R
authors.initials: R
authors.lastname: Somech
mesh_terms: D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D002999:Clone Cells / Q000276:immunology; D016572:Cyclosporine / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D020869:Gene Expression Profiling; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016572:Cyclosporine