Challenges in pig-to-human kidney xenotransplantation – Authors' reply

In our long-term decedent studies, we are using immunosuppression intended to provide long-term xenograft survival combined with porcine thymus transplant, which is intended to diminish specific anti-pig T-cell responses and reduce the need for intense immunosuppression long term.3 In their Correspondence, Chih-Yu Yang and colleagues comment on gene homology (and use of the Banff Human Organ Transplant panel adapted for porcine–human cross-species analysis for transcriptomics studies) and the rationale of using fold change. In our study, the differential expression analysis was carried out using the DESeq function (DESeq2 package) and a Wald test to compare gene expression between conditions of interest, after accounting for cross-species hybridisation. Differentially expressed genes were identified from the linear fitting after computing fold change for the contrast of interest and ranking genes with significant changes in expression level by false discovery rate p value, according to previous studies.4,5 The results presented in the volcano plots showed how much a gene's expression changed in the comparison between the xenografts with the controls of interest including the preimplantation biopsy from the contralateral kidney from the Gal-KO pigs.