BACKGROUND: Cytomegalovirus (CMV) is a major cause of morbidity in transplant recipients. An immunologic predictor of protection against CMV reactivation or disease is highly desirable. METHODS: Thirty-eight allogeneic hematopoietic stem cell transplant recipients at risk of CMV disease were prospectively monitored using whole blood CMV-DNA polymerase chain reaction assay, lymphocyte proliferation assay (LPA), interferon gamma enzyme-linked immunospot assay (ELISPOT), and flow cytometric enumeration of CMV-specific CD69+interferon (IFN)gamma+CD4, CD8, natural killer cells, and gammadelta T cells. RESULTS: Twenty-one subjects developed > or =1 episode of CMV viremia and 4 developed disease during 360 days of follow-up. Among CMV-seropositive recipients, positive CMV-LPA before transplantation correlated with higher risk of developing viremia after transplantation (P = .02). In contrast, after transplantation, reconstitution of CMV-LPA was significantly associated with absence of CMV viremia over 360 days of follow-up (P = .04) and with faster clearance of viremia during individual episodes of CMV reactivation (P = .03). Reconstitution of CMV-specific natural killer cells was also associated with absence of CMV viremia over 360 days of study (P = .04) but not with faster clearance of viremia. CMV-specific CD4, CD8, gammadelta T cells, and ELISPOT values were not significantly different in viremic subjects, compared with the corresponding values in nonviremic subjects, at any time point. CONCLUSIONS: To our knowledge, this is the first study to prospectively compare multiple measures of innate and adaptive immune responses in hematopoietic stem cell transplant recipients with CMV viremia. The strongest immune correlates with protection against CMV viremia in hematopoietic stem cell transplant recipients are reconstitution of CMV-specific T cell memory responses (LPA) and recovery of natural killer cell function. In contrast, positive CMV-LPA before transplantation may be a marker of high risk of CMV reactivation after transplantation.
BACKGROUND: Cytomegalovirus (CMV) is a major cause of morbidity in transplant recipients. An immunologic predictor of protection against CMV reactivation or disease is highly desirable. METHODS: Thirty-eight allogeneic hematopoietic stem cell transplant recipients at risk of CMV disease were prospectively monitored using whole blood CMV-DNA polymerase chain reaction assay, lymphocyte proliferation assay (LPA), interferon gamma enzyme-linked immunospot assay (ELISPOT), and flow cytometric enumeration of CMV-specific CD69+interferon (IFN)gamma+CD4, CD8, natural killer cells, and gammadelta T cells. RESULTS: Twenty-one subjects developed > or =1 episode of CMV viremia and 4 developed disease during 360 days of follow-up. Among CMV-seropositive recipients, positive CMV-LPA before transplantation correlated with higher risk of developing viremia after transplantation (P = .02). In contrast, after transplantation, reconstitution of CMV-LPA was significantly associated with absence of CMV viremia over 360 days of follow-up (P = .04) and with faster clearance of viremia during individual episodes of CMV reactivation (P = .03). Reconstitution of CMV-specific natural killer cells was also associated with absence of CMV viremia over 360 days of study (P = .04) but not with faster clearance of viremia. CMV-specific CD4, CD8, gammadelta T cells, and ELISPOT values were not significantly different in viremic subjects, compared with the corresponding values in nonviremic subjects, at any time point. CONCLUSIONS: To our knowledge, this is the first study to prospectively compare multiple measures of innate and adaptive immune responses in hematopoietic stem cell transplant recipients with CMV viremia. The strongest immune correlates with protection against CMV viremia in hematopoietic stem cell transplant recipients are reconstitution of CMV-specific T cell memory responses (LPA) and recovery of natural killer cell function. In contrast, positive CMV-LPA before transplantation may be a marker of high risk of CMV reactivation after transplantation.
Authors: Raphael Itzykson; Marie Robin; Helene Moins-Teisserenc; Marc Delord; Marc Busson; Aliénor Xhaard; Flore Sicre de Fontebrune; Régis Peffault de Latour; Antoine Toubert; Gérard Socié Journal: Haematologica Date: 2014-09-26 Impact factor: 9.941
Authors: Sara Cantisán; Carmen Martín; María C Romero-Sánchez; Sara Ferrando-Martínez; Francisco Martínez; Antonio Rivero; Antonio Torres; Rafael Solana; Julián Torre-Cisneros Journal: Clin Vaccine Immunol Date: 2012-10-10
Authors: Inmaculada Gayoso; Sara Cantisán; Carolina Cerrato; Joaquín Sánchez-García; Carmen Martin; Rafael Solana; Antonio Torres-Gomez; Julian Torre-Cisneros Journal: Clin Dev Immunol Date: 2013-02-02