Your browser doesn't support javascript.
loading
A Three-Gene Assay for Monitoring Immune Quiescence in Kidney Transplantation.
Roedder, Silke; Li, Li; Alonso, Michael N; Hsieh, Szu-Chuan; Vu, Minh Thien; Dai, Hong; Sigdel, Tara K; Bostock, Ian; Macedo, Camila; Metes, Diana; Zeevi, Adrianna; Shapiro, Ron; Salvatierra, Oscar; Scandling, John; Alberu, Josefina; Engleman, Edgar; Sarwal, Minnie M.
Afiliación
  • Roedder S; Department of Surgery, Division of Transplant Surgery, University of California San Francisco, San Francisco, California;
  • Li L; Department of Biostatistics, Mount Sinai School of Medicine, New York, New York;
  • Alonso MN; Department of Pathology, Stanford University, Palo Alto, California;
  • Hsieh SC; Department of Surgery, Division of Transplant Surgery, University of California San Francisco, San Francisco, California;
  • Vu MT; Department of Surgery, Division of Transplant Surgery, University of California San Francisco, San Francisco, California;
  • Dai H; Department of Surgery, Division of Transplant Surgery, University of California San Francisco, San Francisco, California;
  • Sigdel TK; Department of Surgery, Division of Transplant Surgery, University of California San Francisco, San Francisco, California;
  • Bostock I; Department of Surgery, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; and.
  • Macedo C; Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
  • Metes D; Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
  • Zeevi A; Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
  • Shapiro R; Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
  • Salvatierra O; Department of Pathology, Stanford University, Palo Alto, California;
  • Scandling J; Department of Pathology, Stanford University, Palo Alto, California;
  • Alberu J; Department of Surgery, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; and.
  • Engleman E; Department of Pathology, Stanford University, Palo Alto, California;
  • Sarwal MM; Department of Surgery, Division of Transplant Surgery, University of California San Francisco, San Francisco, California; minnie.sarwal@ucsf.edu.
J Am Soc Nephrol ; 26(8): 2042-53, 2015 Aug.
Article en En | MEDLINE | ID: mdl-25429124
Organ transplant recipients face life-long immunosuppression and consequently are at high risk of comorbidities. Occasionally, kidney transplant recipients develop a state of targeted immune quiescence (operational tolerance) against an HLA-mismatched graft, allowing them to withdraw all immunosuppression and retain stable graft function while resuming immune responses to third-party antigens. Methods to better understand and monitor this state of alloimmune quiescence by transcriptional profiling may reveal a gene signature that identifies patients for whom immunosuppression could be titrated to reduce patient and graft morbidities. Therefore, we investigated 571 unique peripheral blood samples from 348 HLA-mismatched renal transplant recipients and 101 nontransplant controls in a four-stage study including microarray, quantitative PCR, and flow cytometry analyses. We report a refined and highly validated (area under the curve, 0.95; 95% confidence interval, 0.92 to 0.97) peripheral blood three-gene assay (KLF6, BNC2, CYP1B1) to detect the state of operational tolerance by quantitative PCR. The frequency of predicted alloimmune quiescence in stable renal transplant patients receiving long-term immunosuppression (n=150) was 7.3% by the three-gene assay. Targeted cell sorting of peripheral blood from operationally tolerant patients showed a significant shift in the ratio of circulating monocyte-derived dendritic cells with significantly different expression of the genes constituting the three-gene assay. Our results suggest that incorporation of patient screening by specific cellular and gene expression assays may support the safety of drug minimization trials and protocols.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunología del Trasplante / Biomarcadores / Terapia de Inmunosupresión / Trasplante de Riñón Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Female / Humans / Male / Middle aged Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunología del Trasplante / Biomarcadores / Terapia de Inmunosupresión / Trasplante de Riñón Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Female / Humans / Male / Middle aged Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos