Successful Treatment of KSHV Inflammatory Cytokine Syndrome (KICS) after Kidney-Liver Transplant: Correlations with HHV8 miRNome and Specific T-Cell Response

In post-transplant patients, HHV-8/KSHV infection is known to cause aggressive tumors, as well as severe non-neoplastic complications. These latter syndromes are driven by HHV-8/KSHV lytic reactivations and related hyper-inflammatory host responses, typically characterized by high viral loads, elevated levels of cytokines and other inflammation biomarkers, cytopenia, organ failure, high fever, and worsening conditions (with no evidence of B-cell neoplasias). These disorders are associated with a high mortality rate, often due to lack of prompt diagnosis, effective therapeutic approaches, and adequate follow up. Indeed, these features resemble most of those defining the so-called KSHV inflammatory cytokine syndrome (KICS), which was recently recognized in HIV-positive patients. Here we describe, for the first time, a case of KICS-like non-neoplastic recurrent complication occurring in an HIV-negative post-transplant patient, which was successfully treated by combination of anti-CD20 monoclonal therapy, antivirals, and modification of immunosuppressive regimen. In addition to clinical and laboratory findings collected during 3-year-long follow up, we also report novel experimental data on HHV-8-specific T-cell dynamics and circulating miRNA profile, showing correlations with clinical course and other laboratory markers (including viral load, CRP and cytokine levels), thus providing useful information about abnormal cellular and cytokine dynamics underlying of HHV-8-associated inflammatory disorders in post-transplant patients. This article is protected by copyright. All rights reserved.