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. 2020 Dec 3;10(1):21150.
doi: 10.1038/s41598-020-78259-5.

Impact of HLA class I allele-level mismatch on viral infection within 100 days after cord blood transplantation

Tomoki Iemura  1 , Yasuyuki Arai  2   3 , Junya Kanda  1 , Toshio Kitawaki  1 , Masakatsu Hishizawa  1 , Tadakazu Kondo  1 , Kouhei Yamashita  1 , Akifumi Takaori-Kondo  1
Affiliations

Impact of HLA class I allele-level mismatch on viral infection within 100 days after cord blood transplantation

Tomoki Iemura et al. Sci Rep. .

Abstract

Viral infection is more frequently reported in cord blood transplantation (CBT) than in transplantation of other stem cell sources, but its precise mechanism related to antiviral host defenses has not been elucidated yet. To evaluate the effect of human leukocyte antigen (HLA) class I allele-level incompatibility on viral infection in CBT, we conducted a single-center retrospective study. Total 94 patients were included, and viral infections were detected in 32 patients (34%) within 100 days after CBT. HLA-C mismatches in graft-versus-host direction showed a significantly higher incidence of viral infection (hazard ratio (HR), 3.67; p = 0.01), while mismatches in HLA-A, -B, or -DRB1 were not significant. Overall HLA class I mismatch was also a significant risk factor and the predictor of post-CBT viral infection (≥ 3 mismatches, HR 2.38, p = 0.02), probably due to the insufficient cytotoxic T cell recognition and dendritic cell priming. Patients with viral infection had significantly worse overall survival (52.7% vs. 72.1%; p = 0.02), and higher non-relapse mortality (29.3% vs. 9.8%; p = 0.01) at 5 years. Our findings suggest that appropriate graft selection as well as prophylaxis and early intervention for viral infection in such high-risk patients with ≥ 3 HLA class I allele-level mismatches, including HLA-C, may improve CBT outcomes.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
The cumulative incidence of viral infection within 100 days of CBT according to each HLA allelic disparity. (A) The cumulative incidence curve of overall viral infections is demonstrated with the median day of occurrence and its range. (B–E) Comparisons of the cumulative incidence as per mismatches for GVH direction in HLA- (B) A, (C) -B, (D) -DRB1, and (E) -C alleles. Hazard ratio (with 95% CI) and p values are demonstrated.
Figure 2
Figure 2
Comparison of the incidence of viral infection according to the combined HLA allelic disparity. (A) The cumulative incidence was compared between the patients with ≥ 3 and < 3 mismatches in HLA class I (HLA-A, -B, and -C). HR was adjusted for HLA-DRB1 and other confounding factors. (B) The incidence was compared between ≥ 3 and < 3 mismatches in HLA-A, -B, and -DR. HR adjusted by HLA-C and other confounders are displayed.
Figure 3
Figure 3
The impact of HLA mismatches on CMV reactivation. The incidence of CMV reactivation is displayed according to the disparity in (A) HLA-C allele and (B) total disparity in HLA class I (HLA-A, -B, and -C).
Figure 4
Figure 4
The impact of viral infection on overall outcome following CBT. Association of viral infection within 100 days of CBT and overall outcomes were analyzed. (A) OS was compared treating viral infection as a time-dependent covariate and demonstrated with Simon–Makuch plot. (B) NRM was compared and displayed using Fine-Gray method treating the relapse as competing risk.
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