title: Evaluation and significance of cytomegalovirus-specific cellular immune response in lung transplant recipients.
abstract: In lung transplant recipients, cytomegalovirus (CMV) has been associated with direct ie, organ and systemic infection/disease, and indirect effects, including predisposition to develop acute rejection episodes and chronic allograft dysfunction. Cellular immune responses have been demonstrated to play a role in the control of CMV replication. We evaluated CMV-specific cellular responses among lung transplant recipients associated with the onset of organ infection/disease. Cellular responses were evaluated by an Elispot assay of 48 specimens from 24 patients. All samples were evaluated beyond 1 year after transplantation; CMV DNA was concomitantly detected in bronchoalveolar lavage (BAL) and whole blood specimens. Each patient received a combined prolonged antiviral prophylaxis with CMV Ig for 12 months and gancyclovir or valgancyclovir for 3 weeks after postoperative day 21. Nine patients (37.5%) showed transient or persistent CMV nonresponses including donor-recipient negative serologic matching in 2 cases. Positive CMV DNA results were observed in 18/48 BAL specimens (37.5%) from 12 patients (50%). A viral load of >10(4) copies/mL was observed in only 3 cases, 2 of whom were positive also on whole blood. Among these 3 patients, 2 were responders and BAL (as well as whole blood) specimens collected subsequently were negative for CMV DNA; 1 nonresponder patient exhibited a viral load of 426,492 copies/mL BAL (DNAemia, <2,000 copies/mL), developed CMV pneumonia (confirmed by histopathology and immunohistochemistry) and died within 28 days. The prevalence of CMV DNA positivity on BAL did not differ in relation to the immune response; the mean viral load on BAL showed significantly higher results among nonresponders than responders, namely, 1.4 × 10(5) ± 2.4 × 10(5) copies/ml versus 7.9 × 10(3) ± 1.4 × 10(4) (P=.02). Evaluation of CMV-specific cellular immune responses by in vitro immunologic monitoring complements virologic monitoring, helping to identify lung transplant recipients at risk of developing organ infection/disease.
authors.affiliation: S.C. Virologia U, Azienda Ospedaliero-Universitaria San Giovanni Battista di Torino, Torino, Italy. cristina.costa@unito.it
authors.forename: C
authors.initials: C
authors.lastname: Costa
authors.forename: S
authors.initials: S
authors.lastname: Astegiano
authors.forename: M E
authors.initials: ME
authors.lastname: Terlizzi
authors.forename: F
authors.initials: F
authors.lastname: Sidoti
authors.forename: A
authors.initials: A
authors.lastname: Curtoni
authors.forename: P
authors.initials: P
authors.lastname: Solidoro
authors.forename: S
authors.initials: S
authors.lastname: Baldi
authors.forename: M
authors.initials: M
authors.lastname: Bergallo
authors.forename: R
authors.initials: R
authors.lastname: Cavallo
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D016009:Chi-Square Distribution; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control / Q000821:virology*; D004279:DNA, Viral / Q000097:blood / Q000302:isolation & purification; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007558:Italy; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D007166:Immunosuppressive Agents