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NDT Advance Access originally published online on March 10, 2008
Nephrology Dialysis Transplantation 2008 23(8):2673-2678; doi:10.1093/ndt/gfn111
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


HLA-DQ3 is a probable risk factor for CMV infection in high-risk kidney transplant patients

Marina Varga1, Katalin Rajczy2, Gábor Telkes1, Márta Hídvégi1, Antal Péter1, Ádám Remport1, Márta Korbonits3, János Fazakas1, Éva Toronyi1, Enikõ Sárváry1, László Kóbori1 and Jenõ Járay1

1 Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary 2 Immunogenetic Department, National Medical Centre, Budapest, Hungary 3 Department of Endocrinology, Barts and the London Medical School, London, UK

Correspondence and offprint requests to: Marina Varga, Transplantation and Surgical Clinic, Semmelweis University, Baross Street 23-25, Budapest 1082, Hungary. E-mail: marisa1{at}freemail.hu



   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 References
 
Background. Cytomegalovirus (CMV) infection in transplant patients with special risk factors remains a major hazard. CMV-seronegative recipients with seropositive donors have the highest risk of developing acute CMV disease. We suggest that the HLA-type may influence the occurrence and the severity of primary CMV infection of these recipients and the measurement of the special HLA-types may be useful in the prediction of acute infection.

Methods. Since 1999 1213 cadaver kidney transplantations have been performed in our clinic. 163 of 1213 recipients were CMV-seronegative (13%) and 129 of them received the kidney from seropositive donors. All 129 patients received CMV infection prophylaxis. Of 129 CMV-seronegative patients 49 developed acute CMV infection (38%) during the first posttransplant year. CMV infection was diagnosed by CMV antigenemia test and serologic measurements (ELISA). The particular HLA-genotypes of the recipients were studied before the transplantation. The occurrence and the severity of CMV infection was investigated in association with HLA-types.

Results. We found different acute CMV infection distribution in the careers and non-careers of investigated HLA-types: HLA-A2, HLA-B12, HLA-Cw7, HLA-DR6 and HLA-DR11, but the differences weren't significant in these HLA-types (P = 0.26, P = 0.37, P = 0.83, P = 0.07 and P = 0.37). While investigating HLA-DQ3, we found that of 68 DQ3-positive patients 32 (47%), of 61 DQ3-negative patients 17 (28%) had acute CMV infection and this difference was found to be significant. This result was confirmed by univariate and multivariate Cox Regression (P = 0.001) and the appropriate significance level was considered by Bonferroni correction.

Conclusions. HLA-DQ3 was found to be an independent predictor of CMV infection. Our data suggest that patients positive for HLA-DQ3 are more susceptible to CMV infection than a comparable group of patients negative for HLA-DQ3. This result was not due to rejection and/or treatment for rejection and wasn't influenced by induction therapy. Although we found more symptomatic infections among DQ3+ patients the difference wasn't significant (P = 0.19). Comparing the gender proportion among all 1213 kidney recipients and among CMV-seronegative recipients we found that the proportion of males is significantly higher among CMV-seronegative recipients (P < 0.001).

Keywords: cytomegalovirus; HLA; kidney transplantation; prophylaxis; risk factors



   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 References
 
Cytomegalovirus (CMV) infection is an important and common complication of solid organ transplantation, which decreases the long-term graft and patient survival [1]. There have been many reports on the risk factors of CMV infection like CMV-serostatus mismatching, the type and high intensity of maintenance immunosuppression, the use of mono- or polyclonal antibodies, graft rejection and/or treatment for rejection, the type of organ transplanted and, possibly, human leukocyte antigen (HLA) mismatching [2,3]. CMV-seronegative recipients (R–), who receive the graft from CMV-seropositive donors (D+), have the highest risk of developing acute CMV disease [4]. Primary CMV infection is often clinically more severe than reactivation or superinfection, thus increasing the possibility of severe CMV disease.

Genetic variability influences susceptibility to several diseases. A widespread range of diseases have been linked with different HLAs, like ankylosing spondylitis, rheumatoid arthritis, coeliac disease, insulin-dependent diabetes mellitus, multiple sclerosis, Goodpastures’ syndrome, narcolepsy, Chagas disease, alopecia, tuberculosis, etc. [5]. Some HLA types protect against certain diseases, such as skin cancer and Kaposi sarcoma (both are virus-related) [6].

This retrospective study of patients receiving renal allograft examines the possible existence of an association between distinct HLA types and the occurrence and severity of primary CMV infection after transplantation in high-risk CMV-seronegative patients (R–/D+). Some of these patients developed acute CMV infection (symptomatic or asymptomatic) in the early post-transplant period (within 4 months), but in some cases the CMV infection developed later, and some patients remained CMV-free for the investigated period. Many factors may be responsible for these events. Since our patients were homogenous in terms of CMV serostatus, immunosuppressive therapy and CMV prophylaxis, we hypothesized that the reason for such difference in the susceptibility to CMV must be due to genetic predisposition, possibly due to HLA-type diversity. The cognition of certain HLA types may be useful in the prediction of acute CMV infection in high-risk patients.

In this study other CMV infection risk factors were also investigated: induction therapy, graft rejection and/or treatment for rejection. These factors may influence the occurrence of acute CMV infection in different HLA-type patients; therefore, we analysed them in association with patients’ HLA types.



   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 References
 
Patients
From January 1999 until December 2006, 1213 renal transplantations were performed from deceased donors; all were first transplantations. Of 1213 kidney recipients, 163 were CMV-seronegative at the time of the transplantation (13% of all recipients). These data are in accordance with known CMV seroprevalence in the Hungarian population [7]. 129 of the CMV-seronegative patients received the graft from CMV-seropositive donors. These 129 high-risk patients were investigated in our study.

Immunosuppressive therapy
The immunosuppressive regimen included calcineurin inhibitor (cyclosporine, 756 patients or tacrolimus, 457 patients), mycophenolate mofetil (MMF) and corticosteroid. For high-risk patients in terms of hyperacute or acute rejection (panel reactive antibody level >85%) induction therapy with thymoglobulin was indicated for 10 days.

CMV prophylaxis
All 129 seronegative kidney recipients with seropositive donors received CMV-infection prophylaxis with ganciclovir p.o. (3 g/day for 3 months) until 2003, then from 2004 valganciclovir (450 or 900 mg/day for 100 days)—the dose was adjusted according to renal function as recommended by the manufacturer.

CMV monitoring
The CMV serostatus of recipients and donors was determined by an enzyme-linked immunoadsorbent assay (ELISA) technique for the IgG titre; later the seroconversion in CMV infection of transplanted patients was proved by anti-CMV IgG and anti-CMV IgM ELISA tests (Biomedica, Diasorin). The diagnosis of acute CMV infection was established by CMV antigenaemia test. CMV antigenaemia was performed by immunocytological assay for the detection of CMV pp 65 antigen in circulating peripherial blood leukocytes (PBL) by the use of monoclonal antibodies (Biotest, Clonab) and anti-mouse immunoglo- bulins (DAKO), the results expressed quantitatively by reporting the number of CMV antigen positive cells per 100 000 PBL [8]. The presence of positive cells indicated CMV infection and promoted i.v. ganciclovir treatment. All patients were monitored by CMV antigenaemia and CMV antibodies tests weekly for 4 months after transplantation during the period of prophylaxis and monthly for 1 year after the end of the prophylactic period.

In the presence of CMV infection 2 x 5 mg/kg body weight per day i.v. ganciclovir (adjusted according to renal function) was administered until no antigen was detected. After CMV seroconversion prophylaxis was discontinued.

The CMV infection was classified into several groups according to Ljungman et al. [9]:

  1. CMV infection was defined as detection of viral proteins in any body fluid or tissue specimen; CMV infection without clinical symptoms but with positive laboratory results was defined as asymptomatic CMV infection.
  2. CMV syndrome was defined as the presence of fever, leukopaenia or/and thrombocytopenia, arthralgia and increase of liver enzymes in combination with positive antigenaemia test.
  3. CMV end-organ disease was defined as a single organ involvement: gastrointestinal disease, hepatitis, pneumonia plus positive antigenaemia test and/or positive histology.

The CMV infection severity was defined as the occurrence of the symptoms and, if occurred, as the above-mentioned classification of the clinical symptoms. The CMV end-organ disease was defined as the most severe infection.

HLA typing
To determine whether CMV infection is related to any HLA specificities, the incidence of active CMV infection and CMV disease was analysed in relation to HLA-A, -B, -C, -DR and -DQ types of the patients. We focused on HLA-A2, HLA-B12, HLA-Cw7, HLA-DR6, HLA-DR11 and HLA-DQ3 types.

HLA-A, -B and -C typing was performed by the standard NIH micro-lymphocytotoxicity method (NIH) [10]. Earlier (before 2006) HLA-DR and -DQ antigens were determined on B-enriched lymphocyte suspensions separated from peripheral blood by the long incubation time cytotoxicity testing [11] and repeated by the DNA technique only in the case of ambiguous result; while now HLA-DR and -DQ antigens were determined by the DNA-based PCR-SSP technique [12].

HLA typing is routinely performed for the recipients before enrolling on the kidney waiting list and for the donors exactly before the transplantation in order to recognize the HLA matching according to guidelines of the European Federation for Immunogenetics and Eurotransplant.

Most often occurring HLA types were analysed in this study analysed the most often occurring HLA types, in order to reach a statistically relevant number of cases. Since HLA-DQ3 has strong linkage disequilibrium with HLA-DR11 [13], we analysed the data concerning HLA-DR11 in complex with HLA-DQ3.

Diagnosis and treatment of acute rejection
Biopsy was performed on clinically suspected rejection (>25% increase in serum creatinine). The histological findings were assessed by using the Banff 1997 classification [14]. Rejection episodes were treated by high-dose intravenous methylprednisolone.

Statistical analysis
Categorical data were statistically analysed using the chi-square test, or Fisher's exact test. The Mann–Whitney U-test was used for comparisons with quantitative variables. Cumulative incidence was estimated by the Kaplan–Meier method. A Cox proportional hazards model was used to identify independent predictors of CMV primary infection with these variables: induction therapy, graft rejection and/or treatment for rejection, HLA type and age. The patients were homogenous in terms of other influencing factors (CMV serostatus, type of immunosuppression, CMV prophylaxis), so these factors were not taken into account in statistical analysis. Univariate and multivariate Cox regression analysis was performed. All P values were two-sided and the appropriate significance level was considered by the Bonferroni correction: values <0.0083 (0.05/6 = 0.0083) were considered statistically significant. Calculations were made using the StatsDirect computer software program (I. Buchan, Cambridge, UK) and SPSS software program.



   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 References
 
Demographic characteristics and CMV infection
Of the all 1213 kidney transplanted patients, 630 are females (52%) and 583 are males (48%); the mean age at the time of transplantation was 47.3 years (range 3–72 years).

Of 163 CMV-seronegative recipients 54 (33%) are females and 109 (67%) are males; the mean age was 37.6 years.

Of 129 patients (R–/D+) who received the graft from CMV-seropositive donors, 41 are females (31%) and 88 are males (69%); the mean age was 39.6 years (range: 4–72). The mean age of 34 CMV-seronegative recipients with seronegative donors (R–/D–) is lower: 33.5 years (range: 3–57).

Although the difference in the gender proportion is negligible among all 1213 recipients, 630 females (48%) and 583 males (52%), the difference in this proportion among CMV-seronegative patients is highly significant: of 163, 54 (33%) are females and 109 (67%) are males (P < 0.001). We had expected more seronegative females than males since the mean age of females (35.6 years) was lower than that of males (41.5 years) in this group and it is well known that the CMV seroprevalence is growing with age [7].

The mean age of CMV-seronegative recipients was lower than that of all 1213 transplant patients (37.6 versus 47.3 years); the difference is highly significant (P < 0.0001). However in Cox regression analysis, the age of recipients did not influence the development of CMV infection.

Incidence of CMV infection
Of 129 CMV-seronegative recipients with seropositive donors 49 (38%) developed acute primary CMV-infection (proved by the CMV antigenaemia test) during the first post-transplant year (average period: 101.6 days post-transplant). Among 34 seronegative patients who had received the graft from seronegative donors, only 1 developed CMV infection with mild symptoms on day 124 post-transplant.

To determine whether CMV infection was related to certain HLA antigens, the incidence of acute CMV infection and CMV disease was analyzed in relation to the presence of HLA-A2, HLA-B12, HLA-Cw7 (Class I) and HLA-DR6, HLA-DR11, HLA-DQ3 (Class II) types (Table 1).


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  		Table 1 CMV infection and the Class I and Class II HLA types, univariate and multivariate Cox proportional hazards analysis

 
The occurrence of CMV infection in patients with HLA-A2, HLA-DR6, HLA-DR11 was higher, while the occurrence in those with HLA-B12 and HLA-Cw7 was lower than that in patients negative for these HLA types, but the differences were not significant. However, a significant difference was found in the HLA-DQ3+ group versus HLA-DQ3 negative patients: of 68 DQ3 positive patients 32 and of 61 DQ3 negative patients 17 had CMV primary infection (P = 0.002) in univariate analysis. The CMV infection occurred significantly more often among HLA-DQ3+ patients. To determine whether these results were influenced by other risk factors, we performed the multivariate Cox regression analysis that showed that the HLA-DQ3 positivity is an independent predictor of CMV acute infection in R–/D+ recipients (Table 2). The cumulative incidence curves estimated by the Kaplan–Meier method showed higher cumulative incidence of acute primary CMV infection in the HLA-DQ3 positive group (black line) versus HLA-DQ3 negative patients (dotted line) (Figure 1).


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  		Table 2 Multivariate Cox proportional hazards analysis

 

Figure 1
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  		Fig. 1 Cumulative incidence of CMV infection of HLA-DQ3 positive patients (black line) and HLA-DQ3 negative patients (dotted line).

 
HLA-DR11 was investigated in complex with HLA-DQ3 since DQ3 has strong linkage disequilibrium with DR11. Of 129 patients, 29 are positive for DR11, and 25 of these 29 are positive for DQ3 as well. Of 29 DR11+ patients 13, and of 25 DR11+ DQ3+ patients, 11 developed CMV infection. The difference between infection of DR11 carriers and DR11 negative patients was not significant (P = 0.37), nor was the difference between DR11+ DQ3+ and DR11–DQ3+ patients (P = 0.50). We found no association between DR11 type and CMV infection.

Among HLA-DQ3+ patients the infection occurred earlier than among patients without DQ3: 78.7 post-transplant days versus 96.9 days (overall P = 0.46). CMV infection occurred earlier in patients positive for HLA-A2, HLA-B12, HLA-DR6, HLA-DR11 (78–97 days, 84– 86 days, 88–102 days, 80–96 days) and later in patients positive for HLA-Cw7 (89–83 days), than in negative groups. But the differences in all investigated HLA-type groups are not significant (P = 0.09, P = 0.9, P = 0.46, P = 0.37 and P = 0.82).

Severity of CMV infection
Of 68 HLA-DQ3+ patients, 32 developed primary CMV infection (47%), 8 of them were CMV end-organ diseases, 16 CMV syndromes [24 symptomatic infections (75%)] and 8 were asymptomatic infections. Of 61 HLA-DQ3– patients 17 (28%) developed CMV infection: only 1 had CMV end-organ disease, 8 had CMV syndromes [9 symptomatic infections (53%)] and 8 infections were asymptomatic. The severity of CMV infection was higher in HLA-DQ3+ patients, but the difference was not significant (P = 0.19) (Table 3).


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  		Table 3 CMV infection severity in different HLA types

 
We did not find a significant difference in the severity (symptomatic versus asymptomatic infection) of infection in patients possessing or not possessing HLA-A2, HLA-B12, HLA-Cw7, HLA-DR6 and HLA-DR11 as well: P = 0.77, P = 0.74, P = 0.19, P = 0.75, P = 1.0 (Table 3).

Acute graft rejection and treatment for rejection
Of 129 patients, 31 (24%) developed acute rejection during the first post-transplant year. All rejections were treated by high-dose intravenous methylprednisolone. Of 68 HLA-DQ3 positive patients, 20 (29%) developed acute rejection; 6 rejection episodes were followed by acute CMV infection within 6 weeks after rejection. Of 61 HLA-DQ3 negative patients, 11 (18%) developed acute rejection; in 8 cases CMV infection developed within 6 weeks after rejection.

We found that the occurrence of CMV infection after rejection did not differ in HLA-DQ3+ and HLA-DQ3– patients. The Cox regression analysis showed that there is no significant difference in the influence of rejection and/or treatment for rejection on the CMV infection in patients possessing or not possessing DQ3 type of HLA (P = 0.14) (Table 2).

Induction therapy
Of 129 R–/D+ recipients, 14 received induction therapy with thymoglobulin that was indicated for 10 days. The Cox regression analysis showed that there was no significant difference in the influence of such therapy on the CMV infection in DQ3-positive versus DQ3-negative patients (Table 2).



   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
References
 
It is well known that the HLA system influences the predisposition for several diseases and infections [15]. In the last two decades findings concerning the association of CMV infection with HLA were reported (Table 4). The authors investigated 15 types of HLA system; 3 of them (HLA-Cw7, HLA-B16 and HLA-B55) were protective against CMV disease [16,17,18], the others (HLA-A2, HLA-A24, HLA-A32, HLA-B7 of donors, HLA-B52, HLA-Bw4, HLA-DR6, HLA-DR11, HLA-DR15) increased the risk of the development of CMV infection [16,19,24]. The results of Kraat et al. and Gomez et al. concerning HLA-DR7 were conflicting [20,23], like the data of Chen et al. versus results of Yamada et al. and Retiere et al. concerning the protective role of HLA-A11 and HLA-B51 [18,22,24]. Boland et al. investigated the HLA type of the donors and found that the recipients of donors positive for HLA-B7 were especially at risk for developing active CMV infection [21].


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  		Table 4 Reports about association of CMV infection and HLA types

 
HLA-A2, HLA-DR6 and HLA-DR11 were also investigated in our study. Contrary to the findings of other authors we found that these HLA types did not have a significant influence on the occurrence and severity of CMV infection, although the P value of HLA-DR6 was almost significant (P = 0.07) in univariate analysis. We investigated the recipients with HLA-Cw7, but our results did not prove significantly the CMV-infection decreasing role of this type, although we found less CMV infections among patients positive for HLA-Cw7 (Table 1) and the infections, if occurred, developed later in this group.

HLA-DQ3 has not been previously investigated, and this HLA type was found to be a significant predictor of CMV infection in our study. The higher CMV susceptibility in HLA-DQ3 positive patients was not influenced by well-known risk factors such as induction therapy, rejection or/and treatment for rejection in the multivariate Cox regression analysis.

The HLA types examined in our study are routinely determined before the kidney transplantation in order to analyse the matching between donor and recipient HLA types. We do not need any additional examination for the determination of HLA-DQ3 before the transplantation. Clinicians knowing the HLA type of the recipient may pay more attention to the patients from high CMV-risk group possessing HLA-DQ3. These findings may be useful in developing rational guidelines for screening, examination frequency and targeted prophylaxis for CMV-seronegative recipients (R–/D+), who are at highest risk for developing severe CMV infection.

Major histocompatibility complex molecules are critical for antigen uptaking, processing and presenting. The association of some HLA alleles with active CMV infection might be due to differential presentation of CMV peptides (gB or IE antigens) by HLA molecules or differential recognition by host CD8+ and CD4+ T lymphocytes [17,18]. A Japanese study suggests that the deficient production of neutralizing antibodies against CMV in certain HLA types may lead to the increased susceptibility [25]. Others suppose that distinct HLA types may enhance the production of TNF-{alpha} giving rise to CMV end-organ diseases [22].

Further studies are required to elucidate the association of HLA types with CMV infection. Reports like ours would provide the clinical human basis for further genomic analyses of infection susceptibility.

Minor differences observed by different authors might be caused by the subtype differences of human CMV. In Hungary the gB subtype 1 was shown to be dominant [26]. The determination of the human CMV subtypes will also be required for the understanding of the complex relationship between HLA types and CMV.



   Acknowledgments
 
We would like to thank Peter Vargha (Gottsegen György National Institute of Cardiology, Budapest) for providing statistical calculations of this study.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

  1. Patel R, Paya CV. Infections in solid-organ transplant recipients. Clin Microbiol Rev (1997) 10:86–124.[Abstract]
  2. Freeman RB, Paya C, Pescovitz MD, et al. Risk factors for cytomegalovirus viraemia and disease developing after prophylaxis in high risk solid-organ transplant recipients. Transplantation (2004) 78:1765–1773.[CrossRef][Web of Science][Medline]
  3. Dickenmann MJ, Cathomas G, Steiger J, et al. Cytomegalovirus infection and graft rejection in renal transplantation. Transplantation (2001) 71:764–747.[Web of Science][Medline]
  4. Humar A, Mazzulli T, Moussa G, et al. Clinical utility of cytomegalovirus (CMV) serology testing in high-risk CMV D+/R– transplant recipients. Am J Transplant (2005) 5:1065–1070.[CrossRef][Web of Science][Medline]
  5. Cruz-Robles D, Reyes PA, Monteon-Padilla VM, et al. MHC class I and class II genes in Mexican patients with Chagas disease. Hum Immunol (2004) 65:60–65.[CrossRef][Web of Science][Medline]
  6. Winchester R, Charron D, Louie L, et al. The role of HLA in influencing the time of development of a particular outcome of HIV-1 infection. In: Genetic diversity of HLA functional and medical implication—Charron D, ed. (1997) Paris, France: EDK Publisher. 423–428.
  7. Varga M, Görög D, Kári D, et al. Viral screening of organ donors and human cytomegalovirus seroprevalence in Hungarian population. Orv Hetil (2001) 47:2631–2634.
  8. Murray BM, Amsterdam D, Gray V, et al. Monitoring and diagnosis of cytomegalovirus infection in renal transplantation. J Am Soc Nephrol (1997) 8:1448–1452.[Abstract]
  9. Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis (2002) 34:1094–1097.[CrossRef][Web of Science][Medline]
  10. Staff I. NIH lymphocyte microcytotoxicity technique. In: Manual of Tissue Typing Technique—Ray JG, Hare DB, eds. (1976) 22–24. Bethesda, Washington, USA.
  11. van Rood JJ, van Leeuwen A, Keuning JJ, et al. The serological recognition of the human MLC determinants using a modified cytotoxicity technique. Tissue Antigens (1975) 5:73–79.[Web of Science][Medline]
  12. Olerup O., Zetterquist H. HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in two hours: an alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantations. Tissue Antigens (1992) 39:225–232.[Web of Science][Medline]
  13. Klitz W, Maiers M, Spellman S, et al. New HLA haplotype frequency reference standards: high-resolution and large sample typing of HLA DR-DQ haplotypes in a sample of European Americans. Tissue Antigens (2003) 62:296–307.[CrossRef][Web of Science][Medline]
  14. Racusen LC, Solez K, Colvin RB. Banff 97 working classification of renal allograft pathology. Kidney Int (1999) 55:713–717.[CrossRef][Web of Science][Medline]
  15. Stastny P, Ball EJ, Dry PJ, et al. The human immune response region (HLA-D) and disease susceptibility. Immunol Rev (1983) 70:113–153.[CrossRef][Web of Science][Medline]
  16. Hodge WG, Boivin JE, Shapiro SH, et al. Laboratory-based risk factors for cytomegalovirus retinitis. Can J Ophtalmol (2004) 39:733–745.
  17. Fan J, Meng XQ, Yang MF, et al. Association of cytomegalovirus infection with human leukocyte antigen genotypes in recipients after allogeneic liver transplantation. Hepatobiliary Pancreat Dis Int (2006) 5:34–38.[Medline]
  18. Retiere C, Lesimple B, Lepelletier D, et al. Association of glycoprotein B and immediate early-1 genotypes with human leukocyte antigen alleles in renal transplant recipients with cytomegalovirus infection. Transplantation (2003) 75:161–164.[CrossRef][Web of Science][Medline]
  19. Roenhorst HW, Tegzess AM, Beelen JM, et al. HLA-DRw6 as a risk factor for active cytomegalovirus but not for herpes simplex virus infection after renal allograft transplantation. BMJ (1985) 291:619–621.[Abstract/Free Full Text]
  20. Kraat YJ, Christiaans MH, Nieman FH, et al. Risk Factors for cytomegalovirus infection and disease in renal transplant recipients: HLA-DR7 and triple therapy. Transpl Int (1994) 7:362–367.[CrossRef][Web of Science][Medline]
  21. Boland GJ, Hene RJ, Ververs C, et al. Factors influencing the occurrence of active CMV infection after organ transplantation. Clin Exp Immunol (1993) 94:306–312.[Web of Science][Medline]
  22. Yamada S, Takatsuka H, Takemoto Y, et al. Association of cytomegalovirus interstitial pneumonitis with HLA-type following allogeneic bone marrow transplantation. Bone Marrow Transplant (2000) 25:861–865.[CrossRef][Web of Science][Medline]
  23. Gomez E, Aguado S, Melon S, et al. Absence of association between HLA-DR7 and cytomegalovirus infection in renal transplant patients. Lancet (1993) 341:1480–1481.[CrossRef][Web of Science][Medline]
  24. Chen Y, Rocha V, Bittencourt H, et al. Relationship between HLA alleles and cytomegalovirus infection after allogenic hematopoietic stem cell transplant. Blood (2001) 96:500–501.
  25. Wada K, Mizuno S, Ohta H, et al. Immune response to neutralizing epitope on human cytomegalovirus glycoprotein B in Japanese: correlation of serologic response with HLA-type. Microbiol Immunol (1997) 41:841–845.[Web of Science][Medline]
  26. Lukacsi A, Tarodi B, Endreffy E, et al. Human cytomegalovirus gB genotype 1 is dominant in congenital infections in south Hungary. J Med Virol (2001) 65:537–542.[CrossRef][Web of Science][Medline]
Received for publication: 1. 6.07
Accepted in revised form: 7. 2.08


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