Abstract
BK virus (BKV) infection after kidney transplantation can cause BKV nephropathy (BKVAN) resulting in graft dysfunction and allograft loss. The treatment for BKVAN is reduction of the immunosuppressive load which increases the risk of kidney transplant rejection. There is no biomarker to monitor BKV activity besides BK viral load. The value of the Enzyme-Linked Immunosorbent Spot (ELISPOT) assay as a tool to monitor the recipient's anti-BKV immune response after transplantation was investigated systematically. Electronic databases, including MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials were searched for studies of ELISPOT evaluating the immune response against BKV. BKV status was categorized as "active BKV infection" and as "resolving BKV infection". Random-effects model meta-analysis was performed to determine the diagnostic performance of the ELISPOT assay, after stratifying patients into groups based on positive and negative ELISPOT results. One-hundred twenty-seven articles were identified of which nine were included. Patients with negative ELISPOT had an increased risk of having active BKV replication (odds ratio of 71.9 (95%-CI 31.0-167.1). Pooled sensitivity was 0.95 (95%-CI 0.89-0.98) and specificity was 0.88 (95%-CI 0.78-0.94). The standardized mean difference of the number of IFN-γ producing cells between patients with active BKV infection compared with patients who had resolving BKV infection was -2.09 (95%-CI -2.50, -1.68). The ELISPOT assay is a useful tool for BKV risk assessment and in combination with BKV load may support clinicians in guiding immunosuppressive therapy in patients with BKV replication.
Highlights
Patient and kidney transplant survival have much improved compared with the previous era due to better immunosuppressive drug therapy and a significant increase in the knowledge of transplantation immunology [1,2,3]
When a negative enzyme-linked immunosorbent spot (ELISPOT) was considered to indicate a positive result for the risk of active BK virus (BKV) infec tion, the pooled positive likelihood ratio (PLR) was 6.3 (95%-CI 3.8–10.4) and the pooled negative likelihood ratio (NLR) was 0.09 (95%-CI 0.05–0.15; Fig. 4)
This study is the first systematic review with meta-analysis of the IFN-γ ELISPOT assay that correlated T cell BKV responsiveness with clinical BKV infection in kidney transplant recipients
Summary
Patient and kidney transplant survival have much improved compared with the previous era due to better immunosuppressive drug therapy and a significant increase in the knowledge of transplantation immunology [1,2,3]. 30–40% of patients develop early BKV replication which manifests as BK viruria, whereas 10–20% will progress to BK viremia if the immune response fails to contain BKV replication. BKV-associated nephropathy (BKVAN) occurs in 1–10% of kidney transplant recipients [10]. The incidence of BKVAN is higher among patients who receive more potent immunosuppression, which is more common these days as more patients with higher immunological risk receive transplants [7, 11,12,13]. The general recommendation is to lower the patient’s net immu nosuppressive state[15], this may increase the donor-specific immune response and result in rejection
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