CMV-specific Cell-mediated Immunity at 3-month Prophylaxis Withdrawal Discriminates D+/R+ Kidney Transplants at Risk of Late-onset CMV Infection Regardless the Type of Induction Therapy.

Abstract

BACKGROUND:

Whether cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) at prophylaxis cessation predicts D+/R+ kidney transplants at risk of late-onset CMV infection after receiving distinct induction therapies is still not well characterized.

METHODS:

We prospectively assessed CMV-specific CMI predicting late-onset CMV infection at prophylaxis withdrawal and at earlier time-points, in 96 consecutive D+/R+ patients receiving either anti-interleukin 2-receptor antibody (anti-IL2RA; n = 50) or rabbit antithymoglobulin (n = 46). CMV-specific CMI was evaluated against CMV antigens (IE-1, pp65) using an IFN-γ ELISpot assay.

RESULTS:

Fourteen (14.6%) of 96 patients developed late-onset CMV infection and 2 (2.1%) of 96 displayed disease. At 3 months, CMV-specific CMI frequencies were significantly lower in patients developing late-onset CMV infection (P < 0.001 for IE-1, P = 0.030 for pp65), regardless the type of induction therapy. Receiver operating characteristic curve analyses showed accurate CMV-specific CMI cutoffs (25 and 130 IFN-γ spots for IE-1 and pp65, respectively) classifying patients into high risk, intermediate risk, or low risk (log-rank = 0.006; hazard ratio, 4.084; 95% confidence interval, 1.431-11.651; P = 0.009), being IE-1 CMI the strongest predictor (odds ratio, 5.554; 95% confidence interval, 1.486-20.766; P = 0.011). Although the profound posttransplant CMV-specific CMI inhibition among rabbit antithymocyte globulin-treated patients precludes its use for risk stratification both before and early after kidney transplant, a similar proportion of at-risk patients could be identified before month 3 within anti-interleukin 2-receptor antibody-treated patients.

CONCLUSIONS:

Monitoring CMV-specific CMI at 3-month prophylaxis cessation discriminates kidney transplant recipient at risk of late-onset CMV infection, regardless the type of induction therapy.

• Authors: Marta Jarque, Edoardo Melilli, Elena Crespo, Anna Manonelles, Nuria Montero, Joan Torras, Josep M Cruzado, Sergi Luque, Salvador Gil-Vernet, Josep M Grinyó, Oriol Bestard
• Journal: Transplantation (Transplantation) Vol. 102 Issue 11 Pg. e472-e480 (Nov 2018) ISSN: 1534-6080 [Electronic] United States
• PMID: 30130330 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Antilymphocyte Serum
• IL2RA protein, human
• Immunosuppressive Agents
• Interleukin-2 Receptor alpha Subunit
• thymoglobulin

Topics

• Aged
• Antibodies (administration & dosage, adverse effects)
• Antilymphocyte Serum (administration & dosage, adverse effects)
• Cytomegalovirus (drug effects, immunology)
• Cytomegalovirus Infections (diagnosis, immunology, prevention & control, virology)
• Drug Administration Schedule
• Enzyme-Linked Immunospot Assay
• Female
• Humans
• Immunity, Cellular (drug effects)
• Immunosuppressive Agents (administration & dosage, adverse effects)
• Induction Chemotherapy
• Interferon-gamma Release Tests
• Interleukin-2 Receptor alpha Subunit (antagonists & inhibitors, immunology)
• Kidney Transplantation (adverse effects, methods)
• Male
• Middle Aged
• Monitoring, Immunologic (methods)
• Prospective Studies
• Risk Factors
• Time Factors
• Treatment Outcome