Plasma IL-10 Levels to Guide Antiviral Prophylaxis Prevention of Late-Onset Cytomegalovirus Disease, in High Risk Solid Kidney and Liver Transplant Recipients

Transplantation. 2016 Jan;100(1):210-6. doi: 10.1097/TP.0000000000000816.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / administration & dosage*
  • Biomarkers / blood
  • Cytomegalovirus Infections / blood
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / prevention & control*
  • Drug Administration Schedule
  • Drug Monitoring / methods*
  • Enzyme-Linked Immunosorbent Assay
  • Ganciclovir / administration & dosage
  • Ganciclovir / analogs & derivatives*
  • Humans
  • Interleukin-10 / blood*
  • Kidney Transplantation / adverse effects*
  • Liver Transplantation / adverse effects*
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Transplant Recipients*
  • Treatment Outcome
  • Up-Regulation
  • Valganciclovir

Substances

  • Antiviral Agents
  • Biomarkers
  • IL10 protein, human
  • Interleukin-10
  • Valganciclovir
  • Ganciclovir