Almeshari K, Pall A, Chaballout A, Elgamal H, Almana H, Alzayer F, Abaalkhail N, Altalhi M
Department of Kidney and Pancreas Transplantation, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Clin Transpl. 2011:395-400.
Development of de novo donor-specific anti-HLA antibody (DSA) with antibody-mediated rejection (AMR) is the most important cause of renal allograft loss. Therefore, DSA monitoring might identify grafts susceptible to chronic humoral injury. However, implementing universal monitoring is logistically difficult, costly, and not yet supported by management guidelines, especially in patients with stable graft function. To gain further insight into humoral alloimmunity in transplant patients, we conducted a single center, retrospective study of AMR due to de novo DSA. We excluded patients without full characterization of the HLA specificities by single antigen solid phase immunoassay, and those where the clinical relevance of the DSA could not be determined. The clinical scenarios preceding AMR, HLA mismatches and alloantibody specificities, the histopathological phenotypes, and graft outcome were studied. We identified 44 renal transplant recipients with indication and protocol biopsies (44 biopsies for cause and 2 protocol biopsies), revealing 46 episodes of AMR and DSA (2 episodes in two patients). Most were late (more than 6 months after transplant). Suboptimal immunosuppression was an important prelude, usually due to non-adherence. DSA to DQ was prevalent and most biopsies were C4d positive. In all, 20 graft losses were attributed to AMR. From this study, we propose DSA monitoring in the patients with the following: (1) an episode of late (> 6 months) rejection; (2) history of non-adherence to immunosuppression; (3) immunosuppression minimization; (4) a class II loci (DR and DQ) mismatch transplant; or, (5) history of previous transplants. Close surveillance and protocol biopsies in those who develop de novo DSA is suggested.
新发供者特异性抗人白细胞抗原抗体（DSA）伴抗体介导的排斥反应（AMR）是肾移植失败的最重要原因。因此，DSA监测可能会识别出易受慢性体液损伤的移植物。然而，进行普遍监测在后勤保障方面存在困难、成本高昂，且尚未得到管理指南的支持，尤其是对于移植肾功能稳定的患者。为了更深入了解移植患者的体液同种免疫，我们进行了一项单中心、关于新发DSA所致AMR的回顾性研究。我们排除了那些未通过单抗原固相免疫测定对HLA特异性进行全面鉴定的患者，以及那些无法确定DSA临床相关性的患者。研究了AMR之前的临床情况、HLA错配和同种抗体特异性、组织病理学表型以及移植物结局。我们确定了44例接受指征性活检和方案性活检的肾移植受者（44次因病因进行的活检和2次方案性活检），发现了46例AMR和DSA发作（两名患者各有2次发作）。大多数发作较晚（移植后6个月以上）。免疫抑制不足是一个重要的前奏，通常是由于不依从。针对DQ的DSA很普遍，大多数活检C4d呈阳性。总共有20例移植物丢失归因于AMR。通过这项研究，我们建议对以下患者进行DSA监测：（1）发生晚期（>6个月）排斥反应的患者；（2）有免疫抑制治疗不依从史的患者；（3）免疫抑制最小化的患者；（4）具有II类基因座（DR和DQ）错配移植的患者；或（5）有既往移植史的患者。建议对新发DSA的患者进行密切监测和方案性活检。
