Risk factors for cytomegalovirus infection and disease in renal transplant recipients: HLA-DR7 and triple therapy

Kraat, Y. J.; Christiaans, M. H. L.; Nieman, Fred; Berg-Loonen, P.M. van den; Hooff, J. P. van; Bruggeman, C. A.

doi:10.1111/j.1432-2277.1994.tb01248.x

Cited by 22 publications

(7 citation statements)

References 18 publications

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“…We and others have observed variations in the incidence, severity, and consequences of viral activity in solid organ transplantation related to HLA matching (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Several authors have observed that the incidence of CMV disease was more common when certain HLA antigens were present (3,6 -8,10 -13).…”

mentioning

confidence: 99%

Cytomegalovirus Disease after Prophylaxis with Oral Ganciclovir in Renal Transplantation

Lowell

Hmiel

Hardinger

et al. 2003

Journal of the American Society of Nephrology

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Abstract. This study assessed the incidence of cytomegalovirus (CMV) disease and associated outcomes after oral ganciclovir prophylaxis in renal transplantation. A retrospective analysis was performed of all adult renal transplant recipients at a single transplant center transplanted between August 16, 1996, and December 31, 2000. CMV disease prophylaxis included ganciclovir 1000 mg orally thrice daily prescribed for 90 d in DϪ/Rϩ cases and 180 d in Dϩ/RϪ and Dϩ/Rϩ cases. Forty (9.1%) of 470 patients studied were diagnosed with CMV disease, which varied significantly by CMV serostatus and number of HLA-DR matches. The highest incidence of disease, 26.2%, was in Dϩ/RϪ patients with zero HLA-DR matches. Five-year graft survival was 56.8% with CMV disease compared with 79.1% without (P Ͻ 0.001). Five-year graft survival with CMV disease was 75.9% with one or two HLA-DR matches versus 16.2% with zero HLA-DR matches (P Ͻ 0.001). CMV remains an important factor in long-term graft survival after oral ganciclovir prophylaxis. However, we have observed that the adverse impact of CMV disease on graft survival is apparent only in patients with zero HLA-DR matches. These results call for the development of new CMV disease prophylaxis and treatment strategies in patients with zero HLA-DR matches. In addition, organ allocation policies discouraging combining CMV-seropositive donors and zero HLA-DR matches may be worth consideration.In a study performed at our transplant center, we demonstrated the efficacy of oral ganciclovir prophylaxis to reduce the incidence of CMV viremia and symptomatic CMV disease in renal transplant recipients (1). CMV viremia was reduced from 100% in untreated patients to 11% in treated patients during prophylaxis. Overall symptomatic CMV disease incidence was 61% in untreated patients and 21% in patients treated with oral ganciclovir prophylaxis after the completion of a 3-mo prophylaxis regimen. Although the incidence of symptomatic CMV disease was significantly reduced by prophylaxis, it was remarkable that disease occurred more commonly when the donor was CMV-seropositive compared with seronegative. We subsequently extended our prophylaxis to 90 d in D -/Rϩ cases and 180 d in Dϩ/RϪ and Dϩ/Rϩ cases. The long-term consequences of the CMV disease that did occur were unknown.We and others have observed variations in the incidence, severity, and consequences of viral activity in solid organ transplantation related to HLA matching (2-16). Several authors have observed that the incidence of CMV disease was more common when certain HLA antigens were present (3,6 -8,10 -13). We have observed that certain matched and mismatched HLA antigens are associated with increased graft loss rates from CMV sero-mismatching (2).To determine the long-term impact of short term oral ganciclovir prophylaxis, the development of CMV disease, and the impact of donor and recipient HLA matching, we have undertaken a retrospective review of the outcomes of patients treated at our center with a uniform oral ganciclovir CMV-proph...

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confidence: 99%

Cytomegalovirus Disease after Prophylaxis with Oral Ganciclovir in Renal Transplantation

Lowell

Hmiel

Hardinger

et al. 2003

Journal of the American Society of Nephrology

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“…Furthermore, the presence of certain HLA class II alleles (eg, DR7) in patients who receive transplants can significantly increase their risk of developing HCMV-associated complications. [7][8][9] In the present study we show that HCMV-specific CD4 ϩ T cells can display an unusual cross-reactivity toward alloantigens and may therefore have the potential to contribute toward transplant rejection or graft-versus-host disease.…”

Section: Introductionmentioning

confidence: 99%

Cross-recognition of human alloantigen by cytomegalovirus glycoprotein-specific CD4+ cytotoxic T lymphocytes: implications for graft-versus-host disease

Elkington

Khanna

2005

Blood

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Presence of the HLA-DR7 allele in patients who receive transplants has been proposed as a risk factor for human cytomegalovirus (HCMV)-associated complications; however, the precise mechanism of this increased risk remains unresolved. Here we show that HLA-DR7-restricted HCMV-specific CD4 ؉ cytotoxic T lymphocytes (CTLs) can display an unusual dual specificity toward a glycoprotein-B (gB) epitope and the alloantigen HLA-DR4. However, no HLA-DR4-specific alloreactivity was observed when the gB-specific CTLs were generated from virus carriers expressing both HLA-DR7 and DR4 alleles. This most likely demonstrates the clonal inactivation of potentially self-reactive T cells in humans. Fine specificity analysis showed that gB-specific CTLs from HLA-DR7 ؉ /DR4 ؊ individuals displayed a distinct pattern of recognition when compared with CTLs from HLA-DR7 ؉ /DR4 ؉ individuals, presumably evading an area of the epitope that mimics a structure presented on HLA-DR4. These data illustrate a possible mechanism for the clinical association between HCMV and graft-versus-host disease.

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“…Several reports have described the association between the occurrence of viral infection and disease and the presence of certain HLA antigens in the host (Stewart, Kelsall et al 1981;Baldwin, Claas et al 1983;Roenhorst, Tegzess et al 1985;Kraat, Christiaans et al 1994;Varga, Rajczy et al 2008). Many HLA antigens, including HLA-A2, HLA-A24, HLA-A32, HLA-B52, HLA-Bw4, HLA-DR6, HLA-DR11, HLA-DR15 and HLA-DQ3, were reported to increase the risk of CMV infection (Roenhorst, Tegzess et al 1985;Chen, Rocha et al 2001;Hodge, Boivin et al 2004;Fan, Meng et al 2006), although there were some conflict among the results (Gomez, Aguado et al 1993).…”

Section: Association Of Hla-dr With Strain-specific Antibodiesmentioning

confidence: 99%

Role of Cytomegalovirus Reinfection in Acute Rejection and CMV Disease After Renal Transplantation

Ishibashi¹,

Suzutani²

2012

Renal Transplantation - Updates and Advances

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Risk factors for cytomegalovirus infection and disease in renal transplant recipients: HLA-DR7 and triple therapy

Cited by 22 publications

References 18 publications

Cytomegalovirus Disease after Prophylaxis with Oral Ganciclovir in Renal Transplantation

Cytomegalovirus Disease after Prophylaxis with Oral Ganciclovir in Renal Transplantation

Cross-recognition of human alloantigen by cytomegalovirus glycoprotein-specific CD4+ cytotoxic T lymphocytes: implications for graft-versus-host disease

Role of Cytomegalovirus Reinfection in Acute Rejection and CMV Disease After Renal Transplantation

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