Aguilera Isabel, Alvarez-Marquez Antonia, Gentil Miguel Angel, Fernandez-Alonso Jorge, Fijo Julia, Saez Carmen, Wichmann Ingeborg, Nuñez-Roldan Antonio
Immunology Service, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Nephrol Dial Transplant. 2008 Jul;23(7):2393-8. doi: 10.1093/ndt/gfm955. Epub 2008 Feb 28.
Chronic humoral rejection is a progressive form of graft injury, with defined diagnostic criteria, the crucial one being the evidence of circulating anti-donor antibodies. These antibodies are mainly directed against human leucocyte antigens (HLA), but other targets have also been described. We previously reported that antibodies against the Glutathione S-transferase T1 (GSTT1) enzyme appear in recipients without the GSTT1 gene who receive a graft from a GSTT1-positive donor. The primary aim of this study was to analyse the role of GSTT1 in cases of antibody-mediated rejection (AMR) in the absence of anti-HLA antibodies. A second objective was to describe the distribution of the GSTT1 enzyme in the human kidney.
Four renal biopsies from four renal transplanted patients with declined renal function and circulating anti-donor GSTT1 antibodies were studied for C4d deposits in sections of paraffin-embedded tissue samples. Anti-donor-specific HLA and MICA antibody detection was done with the Luminex platform and anti-GSTT1 antibodies were tested by indirect immunofluorescence on rat tissues and ELISA assay. DNA of the patients was extracted for GSTT1 genotyping.
Four patients with the GSTT1 donor/recipient mismatch developed anti-GSTT1 antibodies 32, 42, 48 and 60 months after the transplant. One patient also had donor-specific anti-HLA antibodies. Their biopsies showed pathologic lesions compatible with chronic antibody-mediated rejection (CAMR), along with positive C4d deposition in peritubular capillaries in three of them, being no valuable in the other case.
This is the first study reporting an association between the appearance of chronic antibody-mediated renal allograft rejection and the occurrence of de novo production of anti-GSTT1 antibodies, in the absence of anti-HLA donor-specific antibodies. This fact suggests a potential role of the GSTT1 system in anti-graft immune response.
慢性体液性排斥反应是移植物损伤的一种进行性形式，有明确的诊断标准，其中关键的一点是存在循环抗供体抗体。这些抗体主要针对人类白细胞抗原（HLA），但也有其他靶点被报道。我们之前报道过，在没有谷胱甘肽S-转移酶T1（GSTT1）基因的受者接受来自GSTT1阳性供体的移植物后，会出现针对GSTT1酶的抗体。本研究的主要目的是分析GSTT1在无抗HLA抗体情况下抗体介导的排斥反应（AMR）病例中的作用。第二个目的是描述GSTT1酶在人肾中的分布情况。
对4例肾功能下降且有循环抗供体GSTT1抗体的肾移植患者的肾活检组织进行石蜡包埋组织切片的C4d沉积研究。采用Luminex平台检测抗供体特异性HLA和MICA抗体，通过大鼠组织间接免疫荧光和ELISA检测抗GSTT1抗体。提取患者的DNA进行GSTT1基因分型。
4例GSTT1供体/受者不匹配的患者在移植后32、42、48和60个月出现了抗GSTT1抗体。1例患者还存在供体特异性抗HLA抗体。他们的活检显示出与慢性抗体介导的排斥反应（CAMR）相符的病理病变，其中3例患者的肾小管周围毛细血管C4d沉积呈阳性，另1例无明显阳性表现。
这是第一项报道在无抗HLA供体特异性抗体的情况下，慢性抗体介导的肾移植排斥反应的出现与抗GSTT1抗体的新生产生之间存在关联的研究。这一事实表明GSTT1系统在抗移植物免疫反应中可能发挥作用。
