Introduction:
The John Cunningham virus (JCV) is an opportunistic pathogen that can cause asymptomatic infections to life-threatening diseases in immunocompromised individuals such as kidney transplant recipients (KTRs). However, it has been neglected in research and not mentioned in KT guidelines. We wanted to test our hypothesis that the presence of JCV could be used as an indicator of overt immunosuppression (IS) and help identify KTRs prone to complications such as infections and malignancies.
Methods:
We performed a cross-sectional study among KTRs aged 18 and above with a history of JCV at University Hospital Centre Zagreb (KBC Zagreb), the biggest transplant center in Croatia, one of the leading countries in kidney transplantation. Data was collected from patients’ paper and electronic medical records at the transplant center, compiled using a Microsoft Excel spreadsheet, and summarized using descriptive statistics.
Results:
Of the total 1400 KTRs on regular check-ups in KBC Zagreb, 93 (6.64%) had a history of JCV. The majority (95.7%) had JC viruria, 19.4% had JC viremia, and 16.1% had both. Coinfection of JCV with other viruses was high: CMV (56.9%), COVID-19 (53.8%), EBV (38.7%), and BKV (35.5%). There were also sporadic cases of coinfection with Influenza A and B and varicella-zoster virus. The main reason for JCV testing was the deterioration in graft function that was associated with inflammatory syndrome in one-third of the cases. During 1 year before the JCV diagnosis, 84% of patients required lowering their calcineurin inhibitor (CIN) dose due to exceeding the target levels. The majority had basiliximab as induction therapy. One-third of the patients had a history of additional IS treatment because of primary immunologic kidney disease or complications after KT. All patients received triple IS maintenance therapy, including CIN, mycophenolate or mTOR inhibitor or azathioprine, and prednisone. The dosage of prednisone was 5 mg daily in 40.9% of patients, but a substantial number received higher doses (48.4%), up to 30 mg daily. Approximately one-third of patients who underwent graft biopsy had graft rejection. In the remaining cases, there were signs of CIN toxicity, infection, recurrence of primary disease, or tubulointerstitial nephritis. Three patients had biopsy-proven polyomavirus nephropathy; all of them had frequent and severe various infections, of which 1 died, and 2 required chronic dialysis. One of them had JC nephropathy (positive SV40 in biopsy finding, JC viremia, and absence of BKV). Two patients developed JCV encephalitis. One of them died despite the IS therapy cessation. The other is alive with a functional allograft. 16% of patients were diagnosed with malignancy following JCV diagnosis. All patients who died (19%) had a median age of 64.5 years and a significant comorbidity burden; the majority had severe infections and sepsis, and half of them had some malignancy.
Conclusions:
Our findings show that the JCV may have an immunomodulatory effect in KTRs, especially when associated with other immunomodulatory viruses, which was common in our study. This indicates a need to reconsider how we clinically interpret the presence of JCV. Some patients had severe clinical presentations, including nephropathy and encephalitis. We could not confirm or refute the hypothesis that JCV indicates excessive IS. Further comparative studies are necessary to explore this.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.