Rejection In Transplant Biopsies Research Articles

Microarray analysis of long non-coding RNA expression in human acute rejection biopsy samples following renal transplantation.

Rejection is still a major obstacle in long-term allograft survival of renal transplant recipients. Long non‑coding RNAs (lncRNAs) are an important class of pervasive RNAs involved in a variety of biological functions, and which are often found to be differentially expressed between healthy and pathological conditions. The aim of this study was to compare the expression profiles of lncRNAs between samples from acute rejection following kidney transplantation and control samples. Three patients were enrolled, diagnosed by renal biopsy with acute rejection upon kidney transplantation. We used lncRNA microarrays to study the lncRNA expression profiles in the kidney biopsies of these patients and in kidneys from healthy donors. Reverse transcription‑quantitative polymerase chain reaction (RT-qPCR) was used to validate the microarray results. In addition, potential functions of the identified lncRNAs were further explored by searching the UCSC, RNAdb, RefSeq and NRED databases. Five candidate lncRNAs displaying differential expression in acute rejection samples were validated by RT-qPCR. The results were in agreement with the microarray data. Among the identified lncRNAs, certain have been previously identified in relevant conditions, thereby supporting previous evidence, but certain may constitute novel biomarker candidates. This is the first report to date using lncRNA microarrays to identify unique expression signatures of acute rejection in transplant biopsies. Our data indicate that lncRNAs are potentially involved in the pathogenesis of acute rejection. Our results may have important implications in the identification of diagnostic biomarkers, as well as in the understanding and treatment of acute rejection following renal transplantation.

Positive C4d Immunostaining of Placental Villous Syncytiotrophoblasts Supports Host-Versus-Graft Rejection in Villitis of Unknown Etiology

ABSTRACT Chronic villitis of unknown etiology (VUE) occurs in 5% of placentas submitted to pathology and is characterized by lymphohistiocytic infiltration of chorionic villi. VUE is associated with fetal growth restriction, preterm birth, and recurrent pregnancy loss. Accumulating evidence indicates that VUE may represent a host-versus-graft reaction analogous to transplant rejection. Pathologists routinely screen for antibody-mediated rejection in transplant biopsies by immunostaining for C4d, which highlights the recognition of donor cells by the host immune system. Since the hemochorial placenta is bathed in maternal blood, we hypothesized that cases of VUE may show C4d deposition onto villous syncytiotrophoblasts (STB). Chronic villitis was diagnosed in 82 of 1986 (4%) singleton placentas submitted to our department from 2007 through 2011. Forty randomly selected cases were gestational age-matched with 40 negative controls. Patient charts were reviewed and representative placental sections were immunostained for C4d. A positive C4d result was defined as circumferential immunostaining of the STB around at least one villous, or strong staining of fetal endothelial cells in the chorionic plate or stem villi. Our data indicate that VUE usually occurs in the 3rd trimester (37 ± 0.5 weeks) and is associated with significantly reduced placental weight (P = 0.006). Positive C4d staining of STB was more common in VUE (35/40, 88%) compared with negative controls (2/40, 5%) (P < 0.0001). It was also more common in multiparous (35/66, 53%) than primiparous (2/14, 14%) women (P < 0.01). Although the precise mechanism remains to be determined, our data support the hypothesis that VUE may represent host-versus-graft rejection by the mother.

Pattern and Evolution of C4d Staining of Ischemic Myocardial Injury: Implications for the Interpretation of Post-Transplant Endomyocardial Biopsies

C4d immunohistochemical staining is a marker of recent classical pathway complement activation that is useful for evaluation of antibody-mediated rejection in transplant biopsies. C4d also stains areas of myocyte necrosis. We describe the pattern and intensity of myocyte, interstitial, and microvascular staining at different stages of ischemic injury/infarction in the non- transplant setting. Thirty autopsies with ischemic injury were reviewed. Nine acute myocardial infarction, 3 contraction band necrosis, 9 subendocardial ischemic, and 9 chronic ischemic injury/scarring cases were stained with polyclonal antibody for C4d. Results: Acute myocardial infarction and subendocardial ischemic injury cases showed strong staining of necrotic myocytes; larger infarcts showed more intense peripheral versus central staining. Subendocardial ischemic injury was easier to quantify versus HE5(2):64-70.]