Association of HLA-DR7 with the Development of a Symptomatic Epstein-Barr Virus (EBV) Infection after Pediatric Renal Transplantation

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Introduction: So far, it is unclear why some patients exhibit pronounced acute clinical EBV-related symptoms during post-transplant EBV primary infection, whilst others remain asymptomatic despite a high, persistent EBV viral load, over months or years. A genetic predisposition is likely. Methods: In the framework of a prospective, multicenter trial among 106 pediatric kidney allograft recipients (aged 11.1 ± 5.9 years), we therefore analyzed the prevalence of HLA class I and II alleles and a potential association of HLA alleles with the development of a symptomatic EBV infection (flu-like symptoms or infectious mononucleosis (IM)) in the first year post-transplant. Results: Patients expressing HLA-DR7 bore a significantly increased risk of developing a symptomatic EBV infection (univariate regression analysis: OR 4.77; 95%-CI 1.60-14.2; p=0.005; multivariate analysis: Fig. 1). The prevalence of the HLA-DR7 allele amounted to 25%. Having a comparable EBV risk constellation, HLA-DR7-positive patients suffered significantly more often (9/26 (35%)) a symptomatic EBV infection than HLA-DR7-negative recipients (8/80 (10%); p=0.008). Asymptomatic patients with a high EBV viral load tended to express HLA-DR7 less frequently than symptomatic patients with a high EBV viral load (3/17 (18%) vs. 6/11 (55%), p=0.095).Figure: [EBV HLA]Conclusions: Pediatric renal transplant recipients expressing HLA-DR7 develop significantly more often a symptomatic EBV infection than HLA-DR7-negative patients, possibly as a consequence of a pronounced immune response which, in the long run, may protect against PTLD. Indeed, HLA-DR7 induces a T helper cell reaction through presentation of EBNA1 (1) and is known to be a protective factor against the development of PTLD (2).