In an ITN supported study recently published in the American Journal of Transplantation a new potential indicator of clinical outcome in renal transplant recipients has been identified (results here). The signature was identified from samples collected under the ITN study, “ITN registry of tolerant kidney transplant recipients” led by Kenneth Newell, MD (results reported here). The findings from this study, titled “Donor-specific indirect pathway analysis reveals a B-cell-independent signature which reflects outcomes in kidney transplant” indicate a role for indirect pathway signaling in predicting outcome.
The direct pathway in transplantation refers to an immune response to donor MHC antigen presentation from the graft, whereas indirect pathway signaling refers to processing and presentation of donor antigens via self-MHCs. The investigators (Haynes et al.) used a trans-vivo delayed-type hypersensitivity (tvDTH) assay to measure the relationship between indirect pathway signaling and clinical outcomes in renal transplant recipients. The tvDTH assay uses the level of swelling in mouse footpads in response to human PBMCs as an indicator of cell-mediated immune activity.
PBMCs from patients representing a progressive spectrum of clinical outcomes (tolerant, on varying levels of immunosuppression, and chronic rejectors; n=45) were measured using the tvDTH assay for immune activity. They found that indirect pathway signaling correlated with clinical outcome in a progressive manner, where indirect pathway regulatory responses increased with improved clinical outcomes, and indirect pathway effector responses decreased. Given these results, the authors put forth a hypothetical model where regulatory responses are more pronounced in patients on less immunosuppression, and the tvDTH assay may represent an in vitro method for identifying patients who are able to be partially withdrawn from immunosuppression.