title: Plasma IL-10 Levels to Guide Antiviral Prophylaxis Prevention of Late-Onset Cytomegalovirus Disease, in High Risk Solid Kidney and Liver Transplant Recipients.
abstract: BACKGROUND
  Immune measurements that distinguish solid organ transplantation (SOT) recipients who control cytomegalovirus (CMV) infection from those who progress to CMV-disease (CMV-dz) may be clinically useful in guiding tailored prevention strategies. We previously reported that elevated plasma levels of the immune-modulator IL-10 are associated with late CMV-dz. Here we evaluate whether IL-10 levels measured soon after prophylaxis discontinuation are predictive of CMV-dz risk.
  
  
  METHODS
  Plasma IL-10 levels were quantitatively measured by ELISA kit in 40 D/R SOT patients. All 40 D/R high-risk patients were prospectively followed for at least 12 months post-SOT: 13 subjects developed CMV-dz, all within 6 months of prophylaxis discontinuation.
  
  
  RESULTS
  IL-10 was detectable at the first post-prophylaxis measurement for 11 of 13 subjects who developed CMV-dz. In contrast, IL-10 was detectable in only 6 of 27 CMV asymptomatic patients. Monitoring IL-10 plasma levels within 1 month prophylaxis suspension appeared to have clinically useful level of 85% sensitivity and 78% specificity.
  
  
  CONCLUSIONS
  The exact role of IL-10 with its multiple immunoregulatory effects during CMV infection is not clear. Moreover, IL-10 production can be influenced by pathological and infectious contexts, and/or anti-rejection immunosuppressant therapy. Despite mechanisms of IL-10 dysregulation may substantially differ among SOT patients, our findings suggest that measurable plasma IL-10 soon after prophylaxis discontinuation may be an adequate indicator of subsequent CMV-dz. If a similar prognostic performance is confirmed in a larger D/R cohort, IL-10 plasma levels could be used to guide the length of prophylaxis, providing a clinically useful means to reduce the incidence of CMV-dz in high risk patients.
authors.affiliation: 1 Department of Medicine, Division of Infectious Diseases, University of Washington Medical Center, Seattle, WA.2 Department of Experimental Therapeutics, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA.3 Division of Biostatistics, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA.
authors.forename: Ajit P
authors.initials: AP
authors.lastname: Limaye
authors.forename: Corinna
authors.initials: C
authors.lastname: La Rosa
authors.forename: Jeff
authors.initials: J
authors.lastname: Longmate
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D003586:Cytomegalovirus Infections / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects*; D016031:Liver Transplantation / Q000009:adverse effects*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D066027:Transplant Recipients; D016896:Treatment Outcome; D015854:Up-Regulation; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; C508609:IL10 protein, human; D016753:Interleukin-10; D000077562:Valganciclovir; D015774:Ganciclovir