Use of molecular mismatch to guide induction therapy

Current immune risk criteria for selecting induction therapy lack precision. Here, we examined the relationship of human leukocyte antigen (HLA) and molecular matching with outcomes in patients treated with different induction regimens and immunosuppressive minimization protocols to inform their potential utility in guiding therapy.

Initial studies evaluating induction therapy suggest the role of HLA matching in immune risk-stratification. However, criteria based on antigen level matching and panel-reactive antibodies are imprecise and risk over-assigning patients to treatment with T-cell-depleting agents. Molecularly defined low-risk patients comprise 19-61% of study cohorts. Across heterogenous induction regimens and immunosuppressive minimization studies, these patients consistently demonstrated low immune event rates, providing the basis for prospective trials to test its utility in guiding the choice of induction regimens.

Granular assessment of immune compatibility using molecular mismatch methods coupled with rapid genotyping technologies may help improve the selection of immunosuppressive regimens but will require prospective confirmation.