Delayed graft function (DGF) is associated with decreased kidney graft survival. We have shown that pre-transplant anti-LG3 autoantibodies were associated with increased risk of DGF and early graft dysfunction in kidney transplant recipients (KTR) and decreased renal function in a murine model of ischemia reperfusion injury (IRI). Now we ask whether pre-transplant titers of anti-LG3 and other transplant-relevant autoantibodies are associated with 1-year graft function in KTR with DGF, and whether anti-LG3 IgGs can enhance renal microvascular rarefaction and fibrosis.We performed a single center, retrospective cohort study in consecutive KTR transplanted between June 1^st 2008 and 2013 without rejection. DGF was defined as the need for dialysis in the first week or failure of sCr to decrease by ˃10% on the first 3 days post-transplant. Anti-LG3, anti-vimentin and anti-angiotensin II type 1 receptors (anti-ATII₁R) were measured immediately prior to transplantation using ELISA. 1 year eGFR was estimated with the 4-variable MDRD equation. Unilateral renal artery clamping for 30 minutes plus contra-lateral nephrectomy were performed in C57Bl/6 mice. Intra-venous injections of anti-LG3 IgGs or control IgGs were performed every other day starting 2 days pre-surgery.Among 130 participants, 39 experienced DGF. There was no association between the titers of three autoantibodies. Elevated pre-transplant anti-LG3 titers (β: -13 ml/min/1.73m², 95% CI: -25, -1 for 3^rd versus 1^st tertile) were associated with reduced 1 year eGFR in patients with DGF (adjusted for donor age) but not in those with immediate graft function, while anti-vimentin and anti-ATII₁R were not. Mice passively transferred with anti-LG3 IgGs had higher BUN levels at day 2 post-IRI (p=0.04), decreased CD31 staining (p<0.001) and increased alpha-SMA staining (p<0.001) on immunohistochemistry at day 7 post-IRI. Together these results demonstrate that anti-LG3 antibodies but not anti-ATII₁R or anti-vimentin are associated with decreased 1-year graft function in patients with DGF. This may be explained by anti-LG3 induced renal microvascular rarefaction and fibrosis in the context of IRI.

CITATION INFORMATION: Yang B, Hamelin K, HÉnault-Rondeau M, Patey N, Turgeon J, Lan S, Pomerleau L, Peng J, Tremblay J, DieudÉ M, HÉbert M.-J, Cardinal H. Anti-LG3 Antibodies Enhance Renal Microvascular Rarefaction, Fibrosis and Dysfunction Associated with Ischemia-Reperfusion Injury. Am J Transplant. 2016;16 (suppl 3).

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