Capillary Dilation and Rarefaction Are Correlated with Intracapillary Inflammation in Antibody-Mediated Rejection

Abstract

Antibody-mediated rejection (ABMR) remains one of the major causes of graft loss after renal transplantation. It is dominated by endothelial damage in microcirculation. Clarifying the mechanism of microcirculating damage is obviously a key step to understand the pathogenesis of ABMR. Here we characterized capillary variation in ABMR and its possible mechanisms. Compared with T cell-mediated rejection and stable grafts, there was a significant dilation and rarefaction in peritubular capillaries (PTCs) of the ABMR group; Image-Pro Plus revealed a significantly larger intra-PTC area. Interestingly, the dilation of PTCs was strongly correlated with the intra-PTC cell counting. Moreover, peritubular capillary inflammation is correlated with in situ T-bet expression, and there was a good correlation between the intra-PTC expression of T-bet and the PTC diameter. HIF-1α up-regulation could be observed in ABMR but it was not necessary for capillary dilation. In general, ABMR is characterized with early capillary dilation and rarefaction; our data confirmed that the dilation is strongly correlated with intracapillary inflammation, which in turn is correlated with in situ T-bet expression. T-bet plays an important role in the development of microcirculating injury, and thus it is a potential target for the treatment of ABMR.

Comparison of Liver Graft Regeneration Between ABO-Compatible and ABO-Incompatible Living Donor Liver Transplantation: A Propensity Score Matching Analysis

“…During ABOi transplantation, acute AMR has been reported frequently in heart, kidney, and pancreatic allografts, manifesting in organ dysfunction and a pathological microvasculature [ 41 , 42 ]. During LT, AMR development is rare due to the ability of the liver to modulate immunological reactions and thus compensate for injury.…”

2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology: Introduction of Antibody-Mediated Rejection

“…The “signature” acute AMR microvascular pathology lesions include endothelial cell hypertrophy/enlargement, capillary dilatation, leukocyte sludging and/or leukocyte margination, and edema. In severe cases, microvascular disruption and interstitial hemorrhage occurs . Linear to granular, portal vein and capillary, inlet venule, and focal sinusoidal and central vein endothelial cell C4d deposition is usually present and required under current criteria.…”

“…Pediatric populations are informative since most original diseases do not recur, making putative chronic AMR recognition easier, especially when candidate lesions differ substantially from typical TCMR, viral hepatitis, and vascular or biliary complications. Persistent/recurrent kidney allograft AMR eventually leads to peritubular capillary basement membrane lamination; capillary rarefaction and replacement fibrosis occur in kidney and heart allografts ().…”

“…Acute AMR manifests consistently across kidney, heart, and pancreas allografts as organ dysfunction and microvascular pathology , recognized as intraluminal pooling and/or margination of various leukocyte subsets (monocytes, macrophages, lymphocytes, neutrophils, and eosinophils) in dilated/irregularly shaped capillaries . Liver allografts exhibit a well‐documented AMR resistance (reviewed in ), accounting for the low incidence of acute AMR.…”

Histopathologic Features that Predict Transplant Glomerulopathy Progression in a Chinese Cohort

“…Tubular HLA-DR staining was evaluated by visually assessing the approximate proportion of tubules. Tubule cell expression of HLA-DR was thought to be positive when stained cells represent ≥10% of the biopsy [10].…”