Safety and Effectiveness of Cytomegalovirus Specific Antigen Induced Interferon-Gamma ELISPOT/ELISA: A Systematic Review

Wonjung Choi1   Joohee Hahn1,2   Worlsook Lee1   Chaemin Shin1*   

1 Division of New Health Technology Assessment, National Evidence-based Healthcare Collaborating Agency, Seoul,
2 Review and assessment research department, Health Insurance Review & Assessment Service, Wonju,

* Corresponding author: Tel: +82-2-2174-2870, Fax: +82-2-2174-2800, E-mail:


Background: This study evaluated the safety and effectiveness of the cytomegalovirus (CMV) Specific Antigen Induced Interferon-Gamma ELISPOT (enzyme-linked immunosorbent spot)/ELISA (enzyme-linked immunosorbent assay) procedure in predicting the risk of CMV infection/disease in immunocompromised patients through a systematic literature review.

Methods: The searched electronic databases included MEDLINE, EMBASE and the Cochrane Library. A total of 884 non-duplicate citations were retrieved and a total of 25 studies (15 cohort studies, 10 cross-sectional studies) were included in this review. Study subjects were selected among patients with solid organ, hematopoietic stem cell transplantation, or those who were on hemodialysis. Data extraction and literature quality assessment were carried out independently by two researchers.

Results: Most of the studies were conducted on patients with solid organ transplants. As it is conducted outside the body, CMV Specific Antigen Induced Interferon-Gamma ELISPOT/ELISA assay was safe. Regarding its effectiveness, most studies on risk analysis based on prognosis-related outcomes reported that the inactive group showed a significantly higher hazard ratio or odds ratio than the active group. Results of Kaplan-Meier survival analysis also showed that the inactive group had a significantly higher incidence of CMV event (CMV infection, CMV disease, other events) than the active group. However, various thresholds for CMV cell immune response were reported, as was a broad range of predictive diagnostic accuracies.

Conclusion: CMV Specific Antigen Induced Interferon-Gamma ELISPOT/ELISA assay has potential to stratify the risk of CMV infection/disease among solid organ transplant patients and to determine a policy for a prophylaxis/preemptive. However, additional literature evidence is needed to establish thresholds for CMV cell immune response and standardized tests.

Figures & Tables

Fig. 1. Flow chart of literature selection process.