Abstract
Background and Aims
Twenty years of transplantation of composite vascularised allografts have revealed the high immunogenicity of the constituent parts, especially the skin.Several researchers have proposed the use of vascular stalk flaps, which allow to performe skin biopsy and diagnose rejection without biopsy of the transplanted solid organ.Pre-existing anti-HLA antibodies represent a serious immunological barrier to successful kidney transplantation.We are not aware of any studies on the diagnosis of antibody-associated acute kidney allograft rejection from deceased donors in recipients with pre-existing antibodies, based on morphological examination of a sentinel skin flap on a vascular stalk.
The Aim: To determine the morphological features of humoral rejection in renal transplant recipients with pre-existing anti-HLA antibodies based on sentinel skin flap biopsy.
Method
Three skin-kidney allografts recipients underwent skin flap biopsy on 2nd day after transplantation. A kidney allograft biopsy was performed on day 7, 30, 60, 90.The results of morphological studies are presented using the Banff classification of renal allograft and skin allograft pathology. All recipients were female; 35, 44, and 57 years old. Two patients were re-transplanted and the main cause of CKD was chronic glomerulonephritis. The third patient, with congenital abnormality of the urinary tract, received her first graft.Pre-existing anti-HLA antibody levels before transplantation were 50%, 60%, 80%, respectively.
Results
All recipients showed signs of humoral rejection of the skin flap with thrombosis of the feeding vascular bundle, phlebitis, predominantly intimal arteritis with median necrosis, detachment and areactive necrosis of epidermis and epithelium of skin appendages. Clinical rejection, similar to the algorithm proposed by Etra J.W. et al. to assess preclinical skin rejection in an animal model (2019), was interpreted as G2 in two cases and G3 in one case. The Banff classification of the skin flap offers a qualitative assessment of certain biopsy parameters, while the kidney graft has qualitative-quantitative criteria for assessing rejection.
When comparing the two classifications, a quantitative gradation of pathological changes in the skin flap according to the parameter of intimal arteritis (v) and immunoreactivity of the C4d marker similar to renal rejection was possible. In histological examination of skin flap biopsies, the degree of vasculitis was assessed in a large feeding artery: in all three cases this parameter was equal to v3. C4d expression was analyzed in the endothelium of microcirculatory blood vessels of the dermis and hypodermis: C4d1 in one case and C4d3 in the other two. The analysis of renal allograft biopsies revealed signs of humoral rejection (v1) only at day 30 in two recipients whose C4d expression in the skin and hypodermis was strong (C4d3).
Conclusion
Antibody-mediated rejection of a vascularized sentinel skin flap in recipients with combined skin-kidney transplantation is characterized by vasculitis affecting a core vascular bundle in the form of endarteritis with necrosis of media,phlebitis and associated thrombosis.Further studies are required to determine the feasibility of using a vascular stalked skin flap in the diagnosis of humoral rejection after renal transplantation.
Role of the IL-33/ST2 pathway in renal allograft rejection
