Clinical Analysis and Proteomic Screening Biomarkers for Graft-Versus-Host Disease After Liver Transplant

Graft-versus-host disease is a serious, fatal complication following liver transplantation. The diagnosis is challenging, owing to nonspecific clinical features and invasive procedures. High-throughput proteomics could provide an effective approach to identifying potential serum biomarkers for graft-versus-host disease.

We retrospectively analyzed the clinical information of 3 patients with graft-versus-host disease treated at our center from 2016 to 2018. We compared serum samples from the 3 patients with the disease, patients with excellent posttransplant outcomes, and healthy controls using mass spectrometry-based proteomics in discovery study. Probable peptides were further identified by a tandem mass spectrometry system and verified by enzyme-linked immunosorbent assay.

Of 343 patients, 3 patients (0.875%) had graft-versus-host disease. Two of these patients died of sepsis and multiorgan failure despite intensive therapy. We observed no correlation between severity of clinical manifestation and prognosis; however, the patients with graft-versus-host disease had early onset and infection and showed worse outcome. Serum peptidome profiling showed 65 differentially expressed peaks among the 3 groups; the 2 peptides with the most significant changes (m/z values of 1950.29 and 2088.16) were further sequenced and identified as ATP citrate lyase and fibrinogen alpha chain. Western blot and enzyme-linked immunosorbent assay showed that both peptides gradually decreased among all groups.

Graft-versus-host disease is a complication of organ and tissue transplantation with a high mortality rate. Our identification of potential biomarkers for graft-versus-host disease associated with liver transplant may aid in diagnosis and help to reduce patient mortality in those cases.