Nanostring gene expression profiling in a mouse model of antibody-mediated rejection of kidney allografts

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 in wild-type C57BL/6 allograft recipients. Allografts from B6.CCR5-/-cG-/- recipients on days 45 and 60 had typical characteristics of chronic graft injury including interstitial collagen deposition and peri-glomerular fibrosis that was accompanied by a fibrogenic transcript signature and late post-transplant production of autoantibodies to many targets, including structural proteins including collagen IV and fibronectin.