Graft Inflammation and Histologic Indicators of Kidney Chronic Allograft Failure: Low-Expressing Interleukin-10 Genotypes Cannot Be Ignored

被引:15
作者
Khan, Faisal [1 ,2 ]
Sar, Aylin [2 ,3 ,4 ]
Gonul, Ipek [2 ,3 ,4 ]
Benediktsson, Hallgrimur [2 ,3 ]
Doulla, Jagdeep
Yilmaz, Serdar [3 ,4 ]
Berka, Noureddine [2 ]
机构
[1] Calgary Lab Serv, Tissue Typing Lab, Calgary, AB T2L 2K8, Canada
[2] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada
[3] Foothills Med Ctr, Calgary, AB, Canada
[4] Univ Calgary, Div Transplantat, Calgary, AB, Canada
关键词
Kidney transplantation; Chronic allograft failure; Cytokine gene polymorphism; Interleukin-10; Interstitial fibrosis; Tubular atrophy; CYTOKINE GENE POLYMORPHISMS; REJECTION; NEPHROPATHY; TRANSPLANTATION; PATHOGENESIS; ASSOCIATION; PROMOTER; RECEPTOR; DISEASE; DAMAGE;
D O I
10.1097/TP.0b013e3181ea391e
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Infiltration of inflammatory cells into the renal allograft interstitium is the biologic hallmark of alloimmune responses that leads to tubulointerstitial injury and subsequent interstitial fibrosis and chronic allograft failure. The proliferation, stimulation, and infiltration of these inflammatory cells are governed by various proinflammatory and regulatory cytokines. We assessed whether the differences in the genes encoding cytokines (producing low, moderate, or high expression profiles) may affect the infiltration of inflammatory cells into the renal allograft and the histologic changes characteristics of chronic allograft failure. Methods. A total of 218 kidney transplant recipients were genotyped for 15 single-nucleotide polymorphisms located in the gene promoter or exonic regions of 10 different cytokines or their receptors. Six-to 12-month posttransplant surveillance biopsies were scored using 11 individual histologic parameters and the combined grade of interstitial fibrosis and tubular atrophy (IF/TA). B-cell, T-cell, and macrophage infiltrates were quantified by immunostaining. Results. The low-expressing interleukin (IL)-10 gene promoter genotypes were found significantly associated with high IF/TA grade (IL-10 - 819 TT; P = 0.035; odds ratio = 3.27; 95% confidence interval 1.1-9.8). At individual histologic indices, recipients carrying low-expressing IL-10 genotypes showed 2.5-fold higher scores for interstitial fibrosis, inflammation, and tubular atrophy. High infiltration of T cells and macrophages but not B cells into the renal allograft interstitium was found strongly associated with the carriage of low-expressing IL-10 genotypes. Conclusions. The results suggest that renal transplant recipients genetically predisposed to low expression of the regulatory cytokine IL-10 are more susceptible to high grades of IF/TA scores, graft inflammation, and high influx of inflammatory cells into the graft interstitium.
引用
收藏
页码:630 / 638
页数:9
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