Universit� degli studi di Modena e Reggio Emilia

KICS from HHV-8: a new diagnostic and therapeutic protocol to save organ transplants

It has just been published in American Journal of Transplantation , the world's leading transplantology journal, a study conducted over the last 12 years at ISMETT with the close collaboration of the ISMETT and RIMED research laboratories and the clinical and laboratory haematology departments of Unimore and the University Hospital of Modena, which has made it possible to define a new cytokine syndrome called KICS (Kaposi sarcoma herpesvirus Inflammatory Cytokine Syndrome) and caused by the HHV8 virus.

Neoplastic and non-neoplastic disease caused by human herpes virus type 8(HHV-8) is a life-threatening complication for solid organ transplant recipients. In 2010, Prof. Mario Luppi, Professor of Blood Diseases at Unimore and Director of the Haematology Operating Unit at the University Hospital of Modena, together with his team, documented in the New England Journal of Medicine the first proven case of transmission of the HHV-8 virus from a kidney donor to two recipients, one of whom developed disseminated Kaposi's sarcoma (SK) , while the other manifested a previously undescribed form of 'viral sepsis'. The latter patient, treated only with antivirals and immunoglobulins, died within a month due to organ failure.

In 2012, this experience was recalled by Prof. Luppi when Dr Alessandra Mularoni, head of the Infectious Diseases Service at the Istituto Mediterraneo per i Trapianti e le Terapie ad Alta Specializzazione (ISMETT-IRCCS) in Palermo, contacted him to discuss a severe non-malignant clinical syndrome related to primary HHV-8 infection. The case concerned a recipient of a combined liver-kidney transplant, but similar situations had also occurred in other patients, mainly liver and, in some cases, lung transplant recipients, in a geographical area endemic for the virus.

Serological screening and molecular surveillance in patients at high risk of donor-transmitted HHV-8 infection, i.e. those who receive an organ from an HHV-8 seropositive donor, ensure early recognition and effective treatment of KICS, with antivirals, monoclonal anti-CD20 antibody, and immunosuppressive drugs, capable of ensuring effective antiviral immune responses and eliminating B lymphocytes, carriers of the viral infection. “The implications of this work will be very important both nationally and internationally, as it may even change screening protocols for organ recipients and donors,” the researchers comment.

“During these years, our very close collaboration has guided us in the management of very difficult clinical cases and we have managed to bring the mortality rate of these severe manifestations close to zero thanks to an innovative early diagnosis and treatment protocol,” comment Prof. Luppi and Dr Mularoni. 

"We have already received contacts from colleagues from Italian and foreign universities for information on this innovative protocol that makes organ transplant recipients safe," continue Luppi and Mularoni. "The results of this study are important because this 'cytokine storm' caused by HHV-8 has similarities with the 'cytokine storm' triggered by other viruses such as Sars CoV2 (COVID virus) and with the one that can frequently occur in patients with haematological malignancies (lymphomas, multiple myeloma, acute lymphoblastic leukaemias) who receive the innovative gene-cell therapies called CAR-T. Biological characterisation studies have already started in our Centres, also with the aim of preventing and treating these complications more effectively in our solid organ transplant patients with viral and haemato-oncological infections, treated with CAR-T”.

This work was also recently awarded at the Italian Congress of Infectious Diseases as best oral communication.

This study was made possible by funding 'National Centre for Gene Therapy and Drugs based on RNA Technology' (CN3 'RNA & Gene Therapy')-Spoke 2 (project no. CN000041, CUP E93C22001080001) National Recovery and Resilience Plan, Mission 4, Prof. Mario Luppi, and Next Generation EU -MUR - National Recovery and Resilience Plan, Mission 4, Component 2 Investment 1.3 - Extended Partnership initiative on Emerging Infectious Diseases INF-ACT (project no. PE000007, CUP B73C22001230006) to Dr Alessandra Mularoni.

https://www.amjtransplant.org/article/S1600-6135%2824%2900697-X/fulltext

Serologic screening and molecular surveillance of Kaposi sarcoma herpesvirus/human herpesvirus-8 infections for early recognition and effective treatment of Kaposi sarcoma herpesvirus-associated inflammatory cytokine syndrome in solid organ transplant recipients - American Journal of Transplantation

Categorie: International - english, Notizie_eng