Anti-LG3 Antibodies Aggravate Renal Ischemia-Reperfusion Injury and Long-Term Renal Allograft Dysfunction

被引：36

作者：

Yang, B. ^{[1
,2
,3
]}

Dieude, M. ^{[1
,2
,3
]}

Hamelin, K. ^{[1
,2
,3
]}

Henault-Rondeau, M. ^{[1
,2
,3
]}

Patey, N. ^{[1
,2
,3
,4
]}

Turgeon, J. ^{[1
,2
,3
]}

Lan, S. ^{[1
,2
,3
]}

Pomerleau, L. ^{[1
]}

Quesnel, M. ^{[1
]}

Peng, J. ^{[1
]}

Tremblay, J. ^{[1
]}

Shi, Y. ^{[1
,3
]}

Chan, J. S. ^{[1
,3
]}

Hebert, M. J. ^{[1
,2
,3
]}

Cardinal, H. ^{[1
,2
,3
]}

机构：

[1] Ctr Hosp Univ Montreal CRCHUM, Res Ctr, Montreal, PQ, Canada

[2] Canadian Natl Transplant Res Program, Edmonton, AB T6G 2E1, Canada

[3] Univ Montreal, Montreal, PQ, Canada

[4] Univ Montreal, Dept Pathol, CHU Ste Justine, Montreal, PQ, Canada

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2016年 / 16卷 / 12期

基金：

加拿大健康研究院;

关键词：

DELAYED GRAFT FUNCTION; ACUTE KIDNEY INJURY; II TYPE-1 RECEPTOR; ISCHEMIA/REPERFUSION INJURY; ACTIVATING ANTIBODIES; TRANSPLANT RECIPIENTS; SYSTEMIC-SCLEROSIS; ACUTE REJECTION; CARDIAC DEATH; NATURAL IGM;

D O I：

10.1111/ajt.13866

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

Pretransplant autoantibodies to LG3 and angiotensin II type 1 receptors (AT1R) 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-LG3 antibodies were associated with an increased risk of delayed graft function (DGF). Pretransplant anti-LG3 antibodies are inversely associated with graft function at 1 year after transplantation in patients who experienced DGF, independent of rejection. Pretransplant anti-AT1R and antivimentin were not associated with DGF or its functional outcome. In a model of renal IRI in mice, passive transfer of anti-LG3 IgG led to enhanced dysfunction and microvascular injury compared with passive transfer with control IgG. Passive transfer of anti-LG3 antibodies also favored intrarenal microvascular complement activation, microvascular rarefaction and fibrosis after IRI. Our results suggest that anti-LG3 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.

引用

页码：3416 / 3429

页数：14

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