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Anti‐LG3 Antibodies Aggravate Renal Ischemia–Reperfusion Injury and Long‐Term Renal Allograft Dysfunction
Author(s) -
Yang B.,
Dieudé M.,
Hamelin K.,
HénaultRondeau M.,
Patey N.,
Turgeon J.,
Lan S.,
Pomerleau L.,
Quesnel M.,
Peng J.,
Tremblay J.,
Shi Y.,
Chan J. S.,
Hébert M. J.,
Cardinal H.
Publication year - 2016
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13866
Subject(s) - medicine , reperfusion injury , ischemia , kidney , antibody , cardiology , immunology
Pretransplant autoantibodies to LG 3 and angiotensin II type 1 receptors ( AT 1R) are associated with acute rejection in kidney transplant recipients, whereas antivimentin autoantibodies participate in heart transplant rejection. Ischemia–reperfusion injury ( IRI ) can modify self‐antigenic targets. We hypothesized that ischemia–reperfusion creates permissive conditions for autoantibodies to interact with their antigenic targets and leads to enhanced renal damage and dysfunction. In 172 kidney transplant recipients, we found that pretransplant anti‐ LG 3 antibodies were associated with an increased risk of delayed graft function ( DGF ). Pretransplant anti‐ LG 3 antibodies are inversely associated with graft function at 1 year after transplantation in patients who experienced DGF , independent of rejection. Pretransplant anti‐ AT 1R and antivimentin were not associated with DGF or its functional outcome. In a model of renal IRI in mice, passive transfer of anti‐ LG 3 IgG led to enhanced dysfunction and microvascular injury compared with passive transfer with control IgG. Passive transfer of anti‐ LG 3 antibodies also favored intrarenal microvascular complement activation, microvascular rarefaction and fibrosis after IRI . Our results suggest that anti‐ LG 3 antibodies are novel aggravating factors for renal IRI . These results provide novel insights into the pathways that modulate the severity of renal injury at the time of transplantation and their impact on long‐term outcomes.