Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Am Soc Nephrol. 2011 Jun;22(6):1168-78. doi: 10.1681/ASN.2010111183. Epub 2011 May 12.
Although T and B cell alloimmunity contribute to transplant injury, autoimmunity directed at kidney-expressed, non-HLA antigens may also participate. Because the specificity, prevalence, and importance of antibodies to non-HLA antigens in late allograft injury are poorly characterized, we used a protein microarray to compare antibody repertoires in pre- and post-transplant sera from several cohorts of patients with and without transplant glomerulopathy. Transplantation routinely induced changes in antibody repertoires, but we did not identify any de novo non-HLA antibodies common to patients with transplant glomerulopathy. The screening studies identified three reactivities present before transplantation that persisted after transplant and strongly associated with transplant glomerulopathy. ELISA confirmed that reactivity against peroxisomal-trans-2-enoyl-coA-reductase strongly associated with the development of transplant glomerulopathy in independent validation sets. In addition to providing insight into effects of transplantation on non-HLA antibody repertoires, these results suggest that pretransplant serum antibodies to peroxisomal-trans-2-enoyl-coA-reductase may predict prognosis in kidney transplantation.
虽然 T 细胞和 B 细胞同种异体免疫会导致移植损伤，但针对肾脏表达的非 HLA 抗原的自身免疫也可能参与其中。由于针对晚期同种异体移植物损伤中非 HLA 抗原的抗体的特异性、流行率和重要性尚未得到很好的描述，我们使用蛋白质微阵列比较了几批有和没有移植性肾小球病的患者移植前和移植后血清中的抗体库。移植通常会引起抗体库的变化，但我们没有发现任何与移植性肾小球病患者共同的新的非 HLA 抗体。筛选研究确定了三种在移植前存在且在移植后持续存在并与移植性肾小球病强烈相关的反应性。ELISA 证实，针对过氧化物酶体-反-2-烯酰-CoA 还原酶的反应性与移植性肾小球病的发展密切相关，在独立验证组中得到了验证。这些结果不仅提供了对移植对非 HLA 抗体库影响的深入了解，还表明移植前血清中针对过氧化物酶体-反-2-烯酰-CoA-还原酶的抗体可能预测肾移植的预后。
