Immunosuppression induced by hepatitis C virus infection reduces acute renal-transplant rejection

Corell, Alfredo; Morales, José; Mandroño, A.; Muñóz, Miguel Ángel Suárez; Andrès, Axel; Fuertes, A; Arnaiz‐Villena, Antonio

doi:10.1016/s0140-6736(95)92520-1

Cited by 49 publications

(14 citation statements)

References 3 publications

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“…Graft survival was similar in both groups, which is in accordance with some publications in literature [14,[19][20][21][22]. If patients with HCV infection have a greater risk of the acute cellular rejection is controversial, with some publications showing a higher incidence of rejection in patients with HCV infection when compared to a HCVnegative control group [13,23,24,27]. In the present study, however there was no statistical difference in the incidence of the acute allograft rejection comparing both groups.…”

Section: Discussionsupporting

confidence: 91%

Long-Term Impact in Hepatitis C Virus Infection in Post Renal Transplantation

Lasmar¹,

Lasmar²,

Lasmar³

et al. 2012

OJOTS

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Purpose: The authors have evaluated the impact of the kidney transplantation associated with chronic hepatitis C virus (HCV) infection, analyzing the complications, patients and graft survival. Methods: Retrospective study with 40 kidney transplant recipients with HCV infection and 40 kidney transplant recipients without HCV infection in the same post transplantation period. Results: The average follow-up after transplantation was 12.3 ± 4.5 years in patients with HCV infection and 12.5 ± 2.9 years in patients without HCV infection (p = 0.49). There was no statistical difference related to age and gender of the recipient nor donor age and type. The current renal function in patients with HCV infection was 47.3 ± 24.9 mL/min and 54.9 ± 27.2 mL/min in the HCV negative group (p = 0.54). The incidence of graft and patient survival was similar in both groups. The main cause of death in both groups was bacterial infection (10% in patients with HCV infection and 12.5% in HCV negative patients (p = 0.63). The most common complication in the two groups were acute allograft rejection and bacterial infection. The incidence of diabetes mellitus did not differ statistically in both groups. Abnormal liver enzymes levels and cirrhosis were observed only in patients with HCV infection. Conclusion: HCV infection did not impact patient or graft survival and post-transplant complications were similar in both groups during a mean follow-up period of 12 years.

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Section: Discussionsupporting

confidence: 91%

Long-Term Impact in Hepatitis C Virus Infection in Post Renal Transplantation

Lasmar¹,

Lasmar²,

Lasmar³

et al. 2012

OJOTS

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“…Corell et al. reported a reduction in peripheral CD4 and CD28 T lymphocytes, mostly in the CD4 CD45RA (naïve T helper cell) subpopulation, in HCV‐positive kidney transplant recipients. The relative reduction in naïve T cells accompanied by impaired lymphocyte proliferative responses is important in the defense against TB.…”

Section: Discussionmentioning

confidence: 99%

Impact of pulmonary and extrapulmonary tuberculosis infection in kidney transplantation: a nationwide population‐based study in Taiwan

Liu

Teng

et al. 2012

Transplant Infectious Dis

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“…Hallmarks of HCV infection include impaired HCV-specific intrahepatic and peripheral T cell responses and a delayed onset of HCV-specific humoral and cellular immunity [ 3 – 11 ]. HCV infection is also associated with impaired immune response against vaccine antigens like HBV and reduction in organ transplant rejection, suggesting a state of mild general immunosuppression [ 12 – 14 ]. Although previous studies found that T cell activation is reduced in HCV-infected people [ 3 – 11 ], mechanisms explaining this immune impairment are not well characterized.…”

Section: Introductionmentioning

confidence: 99%

Conserved Motifs within Hepatitis C Virus Envelope (E2) RNA and Protein Independently Inhibit T Cell Activation

et al. 2015

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T cell receptor (TCR) signaling is required for T-cell activation, proliferation, differentiation, and effector function. Hepatitis C virus (HCV) infection is associated with impaired T-cell function leading to persistent viremia, delayed and inconsistent antibody responses, and mild immune dysfunction. Although multiple factors appear to contribute to T-cell dysfunction, a role for HCV particles in this process has not been identified. Here, we show that incubation of primary human CD4+ and CD8+ T-cells with HCV RNA-containing serum, HCV-RNA containing extracellular vesicles (EVs), cell culture derived HCV particles (HCVcc) and HCV envelope pseudotyped retrovirus particles (HCVpp) inhibited TCR-mediated signaling. Since HCVpp’s contain only E1 and E2, we examined the effect of HCV E2 on TCR signaling pathways. HCV E2 expression recapitulated HCV particle-induced TCR inhibition. A highly conserved, 51 nucleotide (nt) RNA sequence was sufficient to inhibit TCR signaling. Cells expressing the HCV E2 coding RNA contained a short, virus-derived RNA predicted to be a Dicer substrate, which targeted a phosphatase involved in Src-kinase signaling (PTPRE). T-cells and hepatocytes containing HCV E2 RNA had reduced PTPRE protein levels. Mutation of 6 nts abolished the predicted Dicer interactions and restored PTPRE expression and proximal TCR signaling. HCV RNA did not inhibit distal TCR signaling induced by PMA and Ionomycin; however, HCV E2 protein inhibited distal TCR signaling. This inhibition required lymphocyte-specific tyrosine kinase (Lck). Lck phosphorylated HCV E2 at a conserved tyrosine (Y613), and phospho-E2 inhibited nuclear translocation of NFAT. Mutation of Y613 restored distal TCR signaling, even in the context of HCVpps. Thus, HCV particles delivered viral RNA and E2 protein to T-cells, and these inhibited proximal and distal TCR signaling respectively. These effects of HCV particles likely aid in establishing infection and contribute to viral persistence.

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Immunosuppression induced by hepatitis C virus infection reduces acute renal-transplant rejection

Cited by 49 publications

References 3 publications

Long-Term Impact in Hepatitis C Virus Infection in Post Renal Transplantation

Long-Term Impact in Hepatitis C Virus Infection in Post Renal Transplantation

Impact of pulmonary and extrapulmonary tuberculosis infection in kidney transplantation: a nationwide population‐based study in Taiwan

Conserved Motifs within Hepatitis C Virus Envelope (E2) RNA and Protein Independently Inhibit T Cell Activation

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