C3d and the Septal Microvasculature as a Predictor of Chronic Lung Allograft Dysfunction

Pathology of pulmonary antibody-mediated rejection: 2012 update from the Pathology Council of the ISHLT

“…[30][31][32][33][34][35][36][37][38][39][40][41][42] In 2002, Magro and colleagues 30 introduced the term ''septal capillary injury syndrome'' to describe alterations in the alveolar spaces and interstitium, usually alveolar septal necrosis, observed in patients with decline in pulmonary function. Complement (C1q, C3, C4d and/or C5b-9) and immunoglobulin deposition of variable intensity were seen in the majority of biopsies.…”

“…31 A study reporting good correlation between C3d and C4d staining by immunoflourescence (IF) and immunohistochemistry (IHC) was also reported by this group. 32,34 In 2006, one study reported a retrospective evaluation of 108 transbronchial biopsy specimens obtained in the first 3 months after transplant from 43 lung transplant recipients stained for C3d and C4d by IHC and evaluated for morphologic features of AMR. 35 There was no correlation of C3d/C4d deposition with the presence of ''septal capillary necrosis,'' ACR, or the development of chronic rejection.…”

Revision of the 1996 Working Formulation for the Standardization of Nomenclature in the Diagnosis of Lung Rejection

“…24 Specifically, C4d deposition has been variably demonstrated as present or absent in the microvasculature of lung biopsies in patients with acute and chronic rejection. 25,26 Specific immunohistochemical sub-endothelial C4d deposition has been suggested as a marker for the involvement of HLA antibodies in lung allograft rejection. 19 However, the patchy nature and low sensitivity and specificity of the C4d staining suggested limited clinical use in protocol biopsies, but raised the possibility of specific C4d deposition serving as a marker of co-existent antibody-mediated rejection in patients with refractory acute cellular rejection.…”

Targeted complement inhibition and microvasculature in transplants: a therapeutic perspective

“…Complement deposition in the septal vasculature of lung transplants is highest in patients with chronic lung transplant rejection [85]. The close correlation between C3d and C4d complement deposition with chronic allograft dysfunction may indicate that humoral rejection is an important contributor to poor outcomes after lung transplantation [85,86].…”

“…Complement deposition in the septal vasculature of lung transplants is highest in patients with chronic lung transplant rejection [85]. The close correlation between C3d and C4d complement deposition with chronic allograft dysfunction may indicate that humoral rejection is an important contributor to poor outcomes after lung transplantation [85,86]. The role of complement driven angiogenesis has also been reported in an orthotopic mouse tracheal model of transplantation [2,40]; both C3 -/-transplant recipients and mice treated with CR2-Crry demonstrated improved recovery of the microvasculature and tissue oxygenation [2,40] (Fig.…”