Association of glycoprotein B and immediate early-1 genotypes with human leukocyte antigen alleles in renal transplant recipients with cytomegalovirus infection.
BACKGROUND
Numerous risk factors for cytomegalovirus (CMV) infection or disease, or both, such as serostatus of donor and recipient, immunosuppressive regimen, or intensity of viral load, have been identified in renal transplant recipients. Additional parameters may be involved, notably, genetic variability of both host and virus, which could modulate the efficacy of the immune response.


METHODS
Active CMV infection was analyzed retrospectively in 634 renal transplant recipients, according to human leukocyte antigen (HLA)-A, HLA-B, and HLA-DR alleles; CMV serostatus; presentation of the disease; and variations in the coding sequences of glycoprotein (g) B and IE1 proteins.


RESULTS
Active infection occurred in 141 of 634 patients: seropositivity of the donor and the recipient were identified as risk factors. Patients carrying the HLA-A11, HLA-A32, or HLA-DR11 allele developed active infection more frequently, whereas none of the patients with the HLA-B16 or HLA-B55 allele was actively infected. Significant independent associations between some genotypes and particular HLA alleles were observed: gB1 was more frequent in the HLA-A24 or HLA-B7 context and underrepresented in patients with HLA-DR11; gB2 was more frequent in HLA-A32 or HLA-DR11 carriers; and an increased frequency of gB3 was observed in the HLA-A29 context. Considering the IE1-2 genotype, increased frequency was noted for HLA-A3 carriers, whereas this type was underrepresented for patients with the HLA-DR11 allele.


CONCLUSIONS
Data strongly suggest that differential presentation of polymorphic gB or IE peptides by HLA molecules or differential recognition by host CD8+ and CD4+ T lymphocytes, or both, should modulate immunologic response and then CMV pathogenesis in renal transplant patients.
Retière
Christelle
C
Inserm U463, Institut de Biologie, Nantes, France.
Lesimple
Béatrice
B
Lepelletier
Didier
D
Bignon
Jean-Denis
JD
Hallet
Marie-Martine
MM
Imbert-Marcille
Berthe-Marie
BM
D000483:Alleles; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000276:immunology; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D016030:Kidney Transplantation / Q000009:adverse effects*; D012189:Retrospective Studies; D015534:Trans-Activators / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000235:genetics*
D006680:HLA Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; C094775:IE-1 protein, murine cytomegalovirus; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus