Successful Treatment of Kaposi Sarcoma–Associated Herpesvirus Inflammatory Cytokine Syndrome After Kidney–Liver Transplant

Correlations With the Human Herpesvirus 8 miRNome and Specific T Cell Response

A. Mularoni, A. Gallo, G. Riva, P. Barozzi, M. Miele, G. Cardinale, G. Vizzini, R. Volpes, P. Grossi, D. Di Carlo, A. Luca, T. Trenti, M. Luppi, P. G. Conaldi

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6 Citations (Scopus)

Abstract

After transplant, patient infection with human herpesvirus 8 (HHV-8) and Kaposi sarcoma–associated herpesvirus (KSHV) is known to cause aggressive tumors and severe nonneoplastic complications. These latter syndromes are driven by HHV-8/KSHV lytic reactivations and related hyperinflammatory 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. These features resemble most of those defining the so-called KSHV-associated inflammatory cytokine syndrome (KICS), which was recently recognized in patients positive for human immunodeficiency virus (HIV). In this report, we describe—for the first time—a case of a KICS-like nonneoplastic recurrent complication occurring after transplant in an HIV-negative patient that was successfully treated by a combination of anti-CD20 monoclonal therapy, antivirals, and modification of the immunosuppressive regimen. In addition to clinical and laboratory findings collected during 3-year follow-up, we report novel experimental data on HHV-8–specific T cell dynamics and circulating microRNA profile, showing correlations with clinical course and other laboratory markers (including viral load, C-reactive protein, and cytokine levels), providing useful information about abnormal cellular and cytokine dynamics underlying HHV-8–associated inflammatory disorders in posttransplant patients.

Original languageEnglish
Pages (from-to)2963-2969
Number of pages7
JournalAmerican Journal of Transplantation
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 1 2017

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Human Herpesvirus 8
Herpesviridae
Cytokines
T-Lymphocytes
Transplants
Viral Load
Biomarkers
HIV
Therapeutics
Immunosuppressive Agents
MicroRNAs
C-Reactive Protein
Antiviral Agents
Neoplasms
B-Lymphocytes
Fever
Inflammation
Mortality
Infection

Keywords

  • clinical research/practice
  • cytokines/cytokine receptors
  • donors and donation: donor-derived infections
  • infection and infectious agents
  • infectious disease
  • molecular biology
  • molecular biology: micro RNA
  • monitoring: immune
  • organ transplantation in general
  • viral: human herpesvirus 8 (HHV-8)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

@article{8bcd3c30cf8a4f30bf595e5514df1f3d,
title = "Successful Treatment of Kaposi Sarcoma–Associated Herpesvirus Inflammatory Cytokine Syndrome After Kidney–Liver Transplant: Correlations With the Human Herpesvirus 8 miRNome and Specific T Cell Response",
abstract = "After transplant, patient infection with human herpesvirus 8 (HHV-8) and Kaposi sarcoma–associated herpesvirus (KSHV) is known to cause aggressive tumors and severe nonneoplastic complications. These latter syndromes are driven by HHV-8/KSHV lytic reactivations and related hyperinflammatory 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. These features resemble most of those defining the so-called KSHV-associated inflammatory cytokine syndrome (KICS), which was recently recognized in patients positive for human immunodeficiency virus (HIV). In this report, we describe—for the first time—a case of a KICS-like nonneoplastic recurrent complication occurring after transplant in an HIV-negative patient that was successfully treated by a combination of anti-CD20 monoclonal therapy, antivirals, and modification of the immunosuppressive regimen. In addition to clinical and laboratory findings collected during 3-year follow-up, we report novel experimental data on HHV-8–specific T cell dynamics and circulating microRNA profile, showing correlations with clinical course and other laboratory markers (including viral load, C-reactive protein, and cytokine levels), providing useful information about abnormal cellular and cytokine dynamics underlying HHV-8–associated inflammatory disorders in posttransplant patients.",
keywords = "clinical research/practice, cytokines/cytokine receptors, donors and donation: donor-derived infections, infection and infectious agents, infectious disease, molecular biology, molecular biology: micro RNA, monitoring: immune, organ transplantation in general, viral: human herpesvirus 8 (HHV-8)",
author = "A. Mularoni and A. Gallo and G. Riva and P. Barozzi and M. Miele and G. Cardinale and G. Vizzini and R. Volpes and P. Grossi and {Di Carlo}, D. and A. Luca and T. Trenti and M. Luppi and Conaldi, {P. G.}",
year = "2017",
month = "11",
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doi = "10.1111/ajt.14346",
language = "English",
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T1 - Successful Treatment of Kaposi Sarcoma–Associated Herpesvirus Inflammatory Cytokine Syndrome After Kidney–Liver Transplant

T2 - Correlations With the Human Herpesvirus 8 miRNome and Specific T Cell Response

AU - Mularoni, A.

AU - Gallo, A.

AU - Riva, G.

AU - Barozzi, P.

AU - Miele, M.

AU - Cardinale, G.

AU - Vizzini, G.

AU - Volpes, R.

AU - Grossi, P.

AU - Di Carlo, D.

AU - Luca, A.

AU - Trenti, T.

AU - Luppi, M.

AU - Conaldi, P. G.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - After transplant, patient infection with human herpesvirus 8 (HHV-8) and Kaposi sarcoma–associated herpesvirus (KSHV) is known to cause aggressive tumors and severe nonneoplastic complications. These latter syndromes are driven by HHV-8/KSHV lytic reactivations and related hyperinflammatory 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. These features resemble most of those defining the so-called KSHV-associated inflammatory cytokine syndrome (KICS), which was recently recognized in patients positive for human immunodeficiency virus (HIV). In this report, we describe—for the first time—a case of a KICS-like nonneoplastic recurrent complication occurring after transplant in an HIV-negative patient that was successfully treated by a combination of anti-CD20 monoclonal therapy, antivirals, and modification of the immunosuppressive regimen. In addition to clinical and laboratory findings collected during 3-year follow-up, we report novel experimental data on HHV-8–specific T cell dynamics and circulating microRNA profile, showing correlations with clinical course and other laboratory markers (including viral load, C-reactive protein, and cytokine levels), providing useful information about abnormal cellular and cytokine dynamics underlying HHV-8–associated inflammatory disorders in posttransplant patients.

AB - After transplant, patient infection with human herpesvirus 8 (HHV-8) and Kaposi sarcoma–associated herpesvirus (KSHV) is known to cause aggressive tumors and severe nonneoplastic complications. These latter syndromes are driven by HHV-8/KSHV lytic reactivations and related hyperinflammatory 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. These features resemble most of those defining the so-called KSHV-associated inflammatory cytokine syndrome (KICS), which was recently recognized in patients positive for human immunodeficiency virus (HIV). In this report, we describe—for the first time—a case of a KICS-like nonneoplastic recurrent complication occurring after transplant in an HIV-negative patient that was successfully treated by a combination of anti-CD20 monoclonal therapy, antivirals, and modification of the immunosuppressive regimen. In addition to clinical and laboratory findings collected during 3-year follow-up, we report novel experimental data on HHV-8–specific T cell dynamics and circulating microRNA profile, showing correlations with clinical course and other laboratory markers (including viral load, C-reactive protein, and cytokine levels), providing useful information about abnormal cellular and cytokine dynamics underlying HHV-8–associated inflammatory disorders in posttransplant patients.

KW - clinical research/practice

KW - cytokines/cytokine receptors

KW - donors and donation: donor-derived infections

KW - infection and infectious agents

KW - infectious disease

KW - molecular biology

KW - molecular biology: micro RNA

KW - monitoring: immune

KW - organ transplantation in general

KW - viral: human herpesvirus 8 (HHV-8)

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U2 - 10.1111/ajt.14346

DO - 10.1111/ajt.14346

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JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

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