HLA Type-Independent Method to Monitor Polyoma BK Virus-Specific CD4+ and CD8+T-Cell Immunity

Hammer, Markus; Brestrich, Gordon; Andree, H; Engelmann, Elisabeth; Rosenberger, Carrie M.; Tillmann, HL; Zwinger, Sandra; Babel, Nina; Nickel, Peter; Volk, Hans‐Dieter; Reinke, Petra

doi:10.1111/j.1600-6143.2005.01221.x

Cited by 64 publications

(49 citation statements)

References 16 publications

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“…Mannon et al (50) found that the RNA transcriptional profiles that were associated with BKV nephropathy indicated a more intense CD8 functional response and more profibrotic response than acute cellular rejection. Hammer et al (69) found that recipients with viral loads Ͼ250,000 copies/ml had detectable BKV-specific CD4 ϩ T cells in peripheral blood, but only the two recipients with BKV-specific CD8 ϩ T cells Ͼ0.1% lost their allografts. The specificity of the cellular response may also be detrimental.…”

Section: Immunologymentioning

confidence: 99%

BK Virus Nephropathy and Kidney Transplantation

Bohl

Brennan

2007

Clinical Journal of the American Society of Nephrology

222

175

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Nephropathy from BK virus (BKV) infection is an evolving challenge in kidney transplant recipients. It is the consequence of modern potent immunosuppression aimed at reducing acute rejection and improving allograft survival. Untreated BKV infections lead to kidney allograft dysfunction or loss. Decreased immunosuppression is the principle treatment but predisposes to acute and chronic rejection. Screening protocols for early detection and prevention of symptomatic BKV nephropathy have improved outcomes. Although no approved antiviral drug is available, leflunomide, cidofovir, quinolones, and intravenous Ig have been used. Retransplantation after BKV nephropathy has been successful.Clin J Am Soc Nephrol 2: S36 -S46, 2007. doi: 10.2215/CJN.00920207 P olyomavirus infection in kidney transplant recipients is of increasing interest and research. Although the two human polyomaviruses, BK virus (BKV) and JC virus (JCV), were reported in 1971 (1,2), their influence and importance were limited. The emergence of polyomavirus nephropathy has coincided with the use of new potent immunosuppressive medications (3,4). It is usually associated with BKV, affects up to 8% of recipients, and frequently results in allograft loss or permanent dysfunction (5). It presents as an asymptomatic gradual rise in creatinine with a tubulointerstitial nephritis that mimics rejection, producing a treatment dilemma. The decrease in immunosuppression that is needed to treat infection is opposite to the increases that are needed to treat rejection.Two studies in kidney transplant recipients who were treated with prednisone and azathioprine in the early 1980s have provided the foundation for much of our current understanding of polyomaviruses in transplant recipients. Hogan et al. (6) and Gardner et al. (7) found that the pretransplantation seroprevalence was 80 to 88% for BKV and 54 to 55% for JCV. The posttransplantation rates of polyomavirus infection were 18 to 44% for BKV and 30 to 35% for JCV. Most polyomavirus infections were asymptomatic and occurred within the first 3 mo after transplantation. BKV infection was associated with a rising creatinine. More than 20 yr ago, Gardner et al. (7) warned, "The detection of polyomavirus infection is important as increased immunosuppression needs to be avoided to prevent possible complications."

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Section: Immunologymentioning

confidence: 99%

BK Virus Nephropathy and Kidney Transplantation

Bohl

Brennan

2007

Clinical Journal of the American Society of Nephrology

222

175

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“…It has lately been hypothesized that development of BKV-capsid protein (VP1)-specific CD8 T-cell response in allograft recipients with BKV plasma replication may be associated with negative PVAN outcome (12). However, prospective data on BKV-specific immunity are lacking in patients with positive BKV viremia or PVAN, and, therefore, the role of BKV-specific T cells on the course of BKV infection and pathogenesis of PVAN remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Prospective Monitoring of Polyomavirus BK Replication and Impact of Pre-Emptive Intervention in Pediatric Kidney Recipients

Ginevri

Azzi

Hirsch

et al. 2007

American Journal of Transplantation

221

222

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Polyoma BK virus (BKV)-associated nephropathy (PVAN) is a relevant cause of poor renal allograft survival.In a prospective analysis, we monitored BKV DNA in blood and urine samples from 62 consecutive pediatric kidney recipients. In patients with BKV replication, we analyzed the impact of reduction of maintenance immunosuppression on viral load kinetics and PVAN in patients with BKV replication. BKV-specific immunity was concomitantly evaluated on blood samples of viremic patients, by measuring the frequency of BKV-specific interferon-c -producing and cytotoxic T cells, and BKV IgG antibody levels. At a median follow-up of 24 months, BK viruria was observed in 39 of 62 patients, while BK viremia developed in 13 patients (21%). In all viremic patients, immunosuppression reduction resulted in the clearance of viremia, and prevented development of PVAN, without increasing the rate of acute rejection or causing graft dysfunction. As a consequence of immunosuppression adjustment, an expansion of BKV-specific cellular immunity was observed that coincided with viral clearance. We conclude that treating pediatric kidney transplant patients pre-emptively with immunosuppression reduction guided by BKV DNA in blood is safe and effective to prevent onset of PVAN. BKV-specific cellular immunity may be useful to guide this intervention.

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“…Hammer and colleagues report on BKV-specific T-cell responses in peripheral blood mononuclear cells (PBMC) of 15 viremic kidney transplant recipients (1). After stimulation with overlapping peptides spanning the viral capsid protein VP1, interferon-c (IFNc )-producing CD4+ T cells were observed in 7 patients (47%), including 2 patients (13%) with a CD8+ T-cell response.…”

Section: Bkv Replication and Cellular Immune Responses In Renal Transmentioning

confidence: 99%