期刊
TRANSPLANTATION
卷 95, 期 4, 页码 580-588出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e318277b2e2
关键词
C4d; Donor-specific anti-HLA antibodies; Microarrays; Gene expression
资金
- Albert Einstein College of Medicine
- Montefiore Medical Center
Background. We investigated the clinical and molecular significance of minimal peritubular capillary (PTC) and isolated glomerular C4d+ staining using microarrays. Methods. Two hundred fifty-five clinically indicated transplant biopsies were included in the analyses. C4d staining was performed on paraffin sections using a polyclonal rabbit anti-C4d antibody. Gene expression profiles in a subset of patients were studied using Affymetrix HuGene 1.0ST arrays. Results. Immunohistochemistry for C4d of 255 biopsies showed 51% C4d negative, 4% minimal PTC C4d+, 15% focal or diffuse PTC C4d+, and 31% isolated glomerular C4d+ biopsies. Patients with minimal and focal/diffuse PTC C4d+ staining had higher frequency of donor-specific anti-HLA antibodies (DSA) (67% and 82%) and antibody mediated rejection (AMR) (66% and 89%) when compared with C4d-negative biopsies (25% and 19%, respectively) (P<0.001). The glomerulitis, interstitial inflammation, and peritubular capillaritis scores were also significantly higher in minimal (0.88, 1.25, and 1.5) and focal/diffuse PTC C4d+ biopsies (0.65, 1.41, and 1.5), compared with C4d-negative biopsies (0.25, 079, and 0.34), respectively. There were no differences in the DSA frequency, AMR rate, or Banff scores between isolated glomerular C4d+ and C4d-negative patients. Although both minimal and focal/diffuse C4d+ biopsies showed increased expression of genes related to the immune response, interferon-gamma and rejection-induced, cytotoxic T cell and constitutive macrophage-associated pathogenesis-based transcripts, there was no activation of immune-response-related genes in isolated glomerular C4d+ biopsies. Conclusion. Minimal PTC C4d+ staining but not isolated glomerular C4d+ staining is associated with AMR, circulating DSAs and immune-response-related gene activation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据