Jackson AM, Kanaparthi S, Burrell BE, et al. - Researchers investigated the impact of donor specific HLA antibody (DSA) following liver transplantation assuming a correlation of DSA IgG subclass characteristics, compared with total DSA IgG, with specific histopathological phenotype(s) of subclinical graft injury. This study thereby comprised 129 stable, arguably “clinically ideal”, pediatric liver recipients at the time of a screening biopsy to enter an immunosuppression withdrawal trial. A positive test for class II DSA was obtained in 65 (50%) individuals. They observed greater HLA mismatch, a histopathological phenotype characterized by the presence of interface activity (with variable degrees of fibrosis), and a transcriptional profile of attenuated T cell mediated rejection in strong correlation with a prominent IgG4 DSA profile. Specifically, those with IgG4 class II DSA MFI sum > 2,000 displayed an odds ratio (OR) of 20.79 and IgG4 subclass composition > 5% displayed an OR of 8.99 (95% CI 2.70-29.9) when compared with those without class II DSA. These data thereby suggest a possible utility of IgG4 DSA as a biomarker to recognize a subset of clinically and biochemically stable liver transplant recipients with histological and transcriptional features suggestive of an active, suboptimally controlled allo-immune response.