Influence of Age and HLA Alleles on the CMV-Specific Cell-Mediated Immunity Among CMV-Seropositive Kidney Transplant Candidates

摘要

To the Editor. We have read with interest the article by Cantisan and co-workers (1) reporting an association between certain human leukocyte antigen class I (HLA-I) alleles (HLA-A1 and HLA-A2) and the presence of pretransplant reactivity in the QuantiFERON-CMV (QF-CMV) assay in cytomegalovirus (CMV)-seropositive solid organ transplant (SOT) candidates. As they acknowledged, this finding might be confounded by the fact that the QF-CMV assay measures CMV-specific interferon-gamma (IFN-gamma)-producing CD8+ T cells mainly targeting viral epitopes on pp65 and immediate-early 1 (IE-1) proteins, whose presentation is restricted through the above-referred alleles (1,2). We sought to determine whether this association remains when CMV-specific IFN-7-producing CD8+ T cell response is assessed by flow cytometry for intracellular staining (ICS) using 15-mer overlapping peptide libraries spanning the entire sequence of pp65 and IE-1 viral proteins as the stimulating antigen. The ICS method is considered the reference procedure for measuring CMV-specific T cell responses, and 15-mer overlapping peptides are potentially presented in a broader HLA-I allele background (2,3). CMV-specific IFN-7-producing CD4+ and CD8+ T cells were enumerated by ICS in 43 CMV-seropositive patients listed for kidney transplantation (details available as Supporting Information). The HLA-A1 and HLA-A2 alleles were present in 10 (24.4%) and 17 (39.5%) patients. The magnitude of CMV-specific CD8+ T cell responses in patients harboring HLA-A1 and/or HLA-A2 alleles was comparable to that observed in patients with HLA-I alleles of other specificities (median 6.59 vs. 4.20 cells/(xL; p-value = 0.309). Interestingly, harboring the HLA-B44 allele (present in 11 [25.6%] patients) was associated with robust CMV-specific CD8+ T cell responses (median 9.88 vs. 4.06 cells/p,L; p-value = 0.016) (Figure 1 A). In fact, it was the only factor found to be associated with the magnitude of such response in a linear regression model (p = 0.366; p-value = 0.020). In turn, older age was not correlated with CMV-specific CD8+ T cell counts (Spearman's rho = -0.223; p-value = 0.155).