Screening for Human Herpesvirus 8 Antibodies in Italian Organ Transplantation Centers

Serraino, Diego; Piselli, Pierluca; Scuderi, M; Gabbrielli, Francesco; Venettoni, Sante; Grossi, Paolo; Costa, Alessandro Nanni; Ippolito, Giuseppe; Infezioni, Studio Italiano Trapianti e

doi:10.1086/426688

Cited by 15 publications

(9 citation statements)

References 9 publications

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“…Our observations on post-transplant KS confirm the need for HHV-8 screening protocols and for guidelines on the clinical management of HHV-8 infection in transplant centres, at least in areas endemic for KS (Serraino et al, 2005). Table 2 Incidence rate ratio (IRR) for Kaposi's sarcoma and corresponding 95% confidence interval (CI) after renal transplantation according to selected characteristics (Italy, 1970(Italy, -2003 The sum does not add up to the total because of missing values.…”

Section: Discussionsupporting

confidence: 70%

Risk of Kaposi's sarcoma and of other cancers in Italian renal transplant patients

Serraino¹,

Piselli²,

Angeletti³

et al. 2005

Br J Cancer

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Section: Discussionsupporting

confidence: 70%

Risk of Kaposi's sarcoma and of other cancers in Italian renal transplant patients

Serraino¹,

Piselli²,

Angeletti³

et al. 2005

Br J Cancer

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“…An important consideration arising from this study, but also raised by others, 33,34 is whether HHV-8 screening should be utilized to identify high-risk recipients or donors. HHV-8 screening could identify individuals with high anti-HHV-8 antibody titers or viremia, characteristics which have been associated with heightened risk of KS among HIV-infected individuals 35 and transplant recipients.…”

Section: Discussionmentioning

confidence: 99%

Kaposi's sarcoma risk among transplant recipients in the United States (1993–2003)

Mbulaiteye¹,

Engels²

2006

Intl Journal of Cancer

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Kaposi's sarcoma (KS) risk is high in immunosuppressed transplant recipients. KS develops in recipients with pre‐existing infection with human herpesvirus 8 (HHV‐8), the causative agent for KS, but it can also occur in recipients infected by donors. The relative importance of these sources of infection in recipients in the United States is unknown. We report recipient and donor characteristics associated with KS among transplant recipients in the United States. KS risk, after solid organ transplantation during 1993–2003, was analyzed using data from the Organ Procurement and Tissue Network. Associations were determined using proportional hazards regression. Sixtyfive KS cases were identified among 234,127 transplants (incidence 8.8 per 100,000 person‐years). Most cases occurred in the first 2 years after transplantation (incidence 12.5 per 100,000 person‐years). KS risk increased steadily with recipient age (ptrend < 0.001) and was associated with the recipient being male (HR 1.8, 95% CI, 1.0–3.2), Hispanic (2.1, 1.1–3.8) and a non‐U.S. citizen (3.9, 1.8–8.6). Mismatch at the HLA‐B locus, but not at HLA‐A or HLA‐DR loci, was associated with heightened risk (HR 3.6, 95%CI 1.1–11 for 1–2 vs. 0 HLA‐B mismatches). KS was unrelated to donor characteristics and was not significantly related to use of specific antirejection medications. Our study found that KS incidence was low among transplant recipients in the United States, but it was associated with recipient age, sex and citizenship, perhaps reflecting pre‐existing HHV‐8 infection. The high KS risk immediately posttransplant and in persons with HLA‐B mismatch highlights the role of immunosuppression and/or immune stimulation in KS pathogenesis. © 2006 Wiley‐Liss, Inc.

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“…However, the disappointing lack of a gold standard in the serologic assays for anti-HHV8 antibodies still represents a major obstacle to routine implementation of screening protocols on organ donors/recipients. [74][75][76] In addition to serology, the donor screening was performed by the search for HHV-8 DNA in the transplanted kidney grafts from 3 of 4 transplant recipients, 9,10 although HHV-8 DNA sequences resulted invariably undetectable in liver grafts from 4 HHV8-seropositive donors. 33 These few available and controversial data do not recommend routine PCR testing for the presence of HHV8 DNA in grafts.…”

Section: Serologic and Molecular Assaysmentioning

confidence: 99%

“…To routinely perform pretransplantation HHV8 screening in the SOT setting, serologic assays for the identification of anti-HHV8 antibodies, either directed to latent LANA antigen or to lytic K8.1 glycoprotein, have appeared to be more accurate than quantitative HHV8 PCR analyses on either serum or PBMC samples. 34,75,76 Considering the variable sensitivity and specificity of HHV8-specific serologic tests reported in the literature, at our center we choose to perform baseline HHV8 screening with both LANA immunofluorescent assay (latent IFA) and K8.1 enzymelinked immunosorbent assay (lytic ELISA), and, to date, these assays have shown a high degree of concordance (Ͼ 90%). However, the disappointing lack of a gold standard in the serologic assays for anti-HHV8 antibodies still represents a major obstacle to routine implementation of screening protocols on organ donors/recipients.…”

Section: Serologic and Molecular Assaysmentioning

confidence: 99%

How I treat HHV8/KSHV-related diseases in posttransplant patients

Riva¹,

Luppi²,

Barozzi³

et al. 2012

Blood

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Posttransplantation human herpesvirus-8 (HHV8)/Kaposi sarcoma herpesvirus (KSHV) primary infection and/or reactivations are associated with uncommon and sometimes fatal, neoplastic, and nonneoplastic diseases. HHV8-related clinical manifestations notably range from Kaposi sarcoma (KS) to either primary effusion lymphoma or multicentric Castleman disease B-cell malignancies, and from polyclonal HHV8-positive plasmacytic lymphoproliferative disorders to bone marrow failure and peripheral cytopenias, associated or not with hemophagocytic syndromes, and to acute hepatitis syndromes. We reviewed the patient series reported in the literature and summarized clinical management aspects, in terms of diagnosis, follow-up, and treatment. We described typical clinical presentations and histopathologic diagnostic features of these diseases, and we discussed the role of HHV8-specific serologic, molecular, and immunologic assays, particularly focusing on recent data from HHV8-specific T-cell monitoring in posttransplantation KS patients. We finally discussed actual therapeutic options, namely, the reduction or discontinuation of immunosuppressive therapy or the switch from calcineurin inhibitors to mTOR inhibitors, as alternatives to antineoplastic chemotherapy, along with the use of antiherpesvirus agents as prophylactic or therapeutic measures, and treatment with rituximab in posttransplantation multicentric Castleman disease patients and non-neoplastic HHV8-associated syndromes. IntroductionHerpesvirus-associated hematologic diseases often represent primary clinical challenges during the multidisciplinary follow-up of posttransplant patients, either with hematopoietic stem cell transplant (HSCT) or with solid organ transplant (SOT). In immunosuppressed organ recipients, latent human ␥-herpesvirus, namely, EBV and human herpesvirus-8 (HHV8)/Kaposi sarcoma herpesvirus (KSHV) are typically responsible for several virus-driven neoplastic proliferations, as well as they may sometimes cause uncommon, but equally life-threatening, non-neoplastic infectious complications. During the past decade, large amounts of experimental evidence have come out on these topics, and some of them have yet begun to influence the clinical behavior, in terms of diagnosis and treatment. Chiefly, EBV-related complications have been extensively studied and discussed, so that now physicians can rely on accurate and updated clinical recommendations, in particular dealing with early diagnosis, monitoring and treatment of EBV ϩ posttransplantation lymphoproliferative diseases (PTLDs). 1 With regards to HHV8, practical management of the virus-associated neoplastic lymphoproliferations has deeply been revised in HIVpositive subjects, 2,3 whereas in SOT and HSCT settings, the diagnostic and therapeutic issues about the various HHV8-driven manifestations (either neoplastic or non-neoplastic) are only occasionally reported in the literature, but most of these diseases revealed to be rapidly lethal if not timely recognized and adequately treated. Indeed, posttra...

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Screening for Human Herpesvirus 8 Antibodies in Italian Organ Transplantation Centers

Cited by 15 publications

References 9 publications

Risk of Kaposi's sarcoma and of other cancers in Italian renal transplant patients

Risk of Kaposi's sarcoma and of other cancers in Italian renal transplant patients

Kaposi's sarcoma risk among transplant recipients in the United States (1993–2003)

How I treat HHV8/KSHV-related diseases in posttransplant patients

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