Journal Article

Relationship of Reconstituted Adaptive and Innate Cytomegalovirus (CMV)-Specific Immune Responses with CMV Viremia in Hematopoietic Stem Cell Transplant Recipients

Michelle A. Barron, Dexiang Gao, Kathryn L. Springer, Julie A. Patterson, Mark W Brunvand, Peter A. McSweeney, Zeng Chang, Anna E. Barón and Adriana Weinberg

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 49, issue 12, pages 1777-1783
Published in print December 2009 | ISSN: 1058-4838
Published online December 2009 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/648423
Relationship of Reconstituted Adaptive and Innate Cytomegalovirus (CMV)-Specific Immune Responses with CMV Viremia in Hematopoietic Stem Cell Transplant Recipients

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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 γ enzyme-linked immunospot assay (ELISPOT), and flow cytometric enumeration of CMV-specific CD69+interferon (IFN)γ+CD4, CD8, natural killer cells, and γδ T cells.

Results. Twenty-one subjects developed ⩾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, γδ 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.

Journal Article.  4350 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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