GATA3 and a dominant regulatory gene expression profile discriminate operational tolerance in human transplantation

• Published in: Clinical immunology (Orlando, Fla.) Vol. 142; no. 2; pp. 117 - 126
• Main Authors: Moraes-Vieira, Pedro Manoel M, Takenaka, Maisa C.S, Silva, Hernandez M, Monteiro, Sandra Maria, Agena, Fabiana, Lemos, Francine, Saitovitch, David, Kalil, Jorge, Coelho, Verônica
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.02.2012; Elsevier
• Subjects: Adult; Aged; Allergy and Immunology; Biological and medical sciences; Female; Forkhead Transcription Factors - blood; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; GATA-3; GATA3 Transcription Factor - blood; GATA3 Transcription Factor - genetics; GATA3 Transcription Factor - metabolism; Gene Expression Profiling; Graft Survival - immunology; Humans; Immunosuppressive Agents - blood; Immunosuppressive Agents - metabolism; Kidney transplantation; Kidney Transplantation - immunology; Leukocytes, Mononuclear - physiology; Male; Middle Aged; Operational tolerance; Receptors, Transforming Growth Factor beta - blood; Receptors, Transforming Growth Factor beta - genetics; Receptors, Transforming Growth Factor beta - metabolism; Retrospective Studies; TGF-β; Th2 Cells - metabolism; Transforming Growth Factor beta1 - blood; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Transplantation Tolerance - genetics; Transplantation Tolerance - immunology; TGF-β; GATA-3; Operational tolerance; Kidney transplantation; Transcription factor GATA3; Human; Immunology; Treatment; Transforming growth factor β; Surgery; Immune tolerance; Gene expression profile
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2011.08.015

Abstract Some organ-transplanted patients achieve a state of "operational tolerance" (OT) in which graft function is maintained after the complete withdrawal of immunosuppressive drugs. We used a gene panel of regulatory/inflammatory molecules ( FOXP3, GATA3, IL10, TGFB1, TGFBR1/ TBX21, TNF and IFNG ) to investigate the gene expression profile in peripheral blood mononuclear cells of renal-transplanted individuals experiencing OT compared to transplanted individuals not displaying OT and healthy individuals (HI). OT subjects showed a predominant regulatory (REG) profile with higher gene expression of GATA3, FOXP3, TGFB1 and TGFB receptor 1 compared to the other groups. This predominant REG gene expression profile displayed stability over time. The significant GATA3 gene and protein expressions in OT individuals suggest that a Th2 deviation may be a relevant pathway to OT. Moreover, the capacity of the REG/INFLAMMA gene panel to discriminate OT by peripheral blood analysis indicates that this state has systemic repercussions.