Pregnancy-shaped donor-directed alloimmune recall in husband-to-wife kidney transplantation: an integrative mechanistic framework.

Spousal living donation expands access to kidney transplantation. Husband-to-wife kidney transplantation (HTW) may have a distinct immunologic context when the recipient has had pregnancies with the current donor, because maternal exposure involves the subset of paternal human leukocyte antigen (HLA) molecules and eplets inherited by the fetus rather than the donor's complete HLA repertoire. We conducted a mechanism-focused narrative review using reproducible PubMed/MEDLINE searches from database inception through 3 July 2026, supplemented by targeted checks of Embase and the Web of Science Core Collection, reference-list screening, and forward and backward citation tracking. Contemporary cohorts generally report acceptable aggregate patient and graft outcomes after modern immunologic screening. However, early donor-specific antibody (DSA) increases, microvascular inflammation (MVI), and antibody-mediated rejection (ABMR) are concentrated among recipients with high panel-reactive antibody or calculated panel-reactive antibody, current or historical DSA, positive flow cytometry crossmatch, or low-level or missed preformed DSA. We propose a hypothesis-generating, two-branch framework. Branch A comprises persistence or rebound of low-level or missed preformed DSA, whereas Branch B comprises reactivation of donor-reactive memory B cells with an anamnestic response; the branches may coexist and converge on DSA-associated endothelial injury, MVI, and ABMR. DSA first detected after transplantation may reflect previously unrecognized preformed antibody, rebound or re-emergence of historical DSA, a memory-mediated anamnestic response, or a primary response to the graft; timing alone cannot distinguish these possibilities. Evidence remains incomplete because no prospective HTW cohort has linked pregnancy-relevant paternal antigen exposure, pretransplant donor-reactive memory B cells, same-specificity posttransplant DSA, and contemporaneous Banff-classified biopsy findings. Shared pregnancy should be treated as a possible donor-related exposure, not a universal risk label; current evidence does not support excluding a husband donor or changing treatment solely on this basis.