Inhibition of De Novo Autoantibody Production Attenuates Chronic Antibody-Mediated Rejection of Kidney Allografts Despite Maintenance of High Donor-Specific Antibody Titers.

ABSTRACT: Acute and chronic antibody mediated rejection (ABMR) continues to decrease clinical kidney graft function and survival. Dysregulated donor-specific antibody (DSA) responses are induced in B6.CCR5^-/- recipients of complete MHC-mismatched A/J kidney allografts with NK cells playing a critical role in the acute ABMR. We tested the role of neutrophils in ABMR by transplanting A/J kidneys to CCR5^-/- mice with a deletion in the neutrophil serine protease cathepsin G. Whereas B6.CCR5^-/- recipients rejected all kidney allografts between days 18-25, 70% of allografts survived beyond day 60 in B6.CCR5^-/-cG^-/- recipients. At days 15-17 post-transplant DSA titers in B6.CCR5^-/-cG^-/- recipients were 24.3-fold higher than those

SUBMITTER: Mitsui Y 

PROVIDER: S-EPMC12262401 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature