C3d and C4d deposition early after lung transplantation

Background: Complement staining as a predictor of antibody-mediated rejection (AMR) after lung transplantation continues to be debated. Methods: In a cohort of 33 lung transplant recipients (LTRs) we assessed early post-transplant (<= 3 months) graft deposition of the complement factors C3d and C4d and correlated staining with clinical outcome. A retrospective analysis of allograft C3d and C4d deposition was performed by an experienced histopathologist blinded to clinical outcomes. Biopsies were graded 0 to 3 based on extent of septal capillary complement staining. Results: Significant C3d and C4d staining (i.e., Grade >= 2 on more than one occasion) was observed in 20 and 11 LTRs, respectively. Complement staining was increased in LTRs with severe primary graft dysfunction or airway infection, but was not associated with acute cellular or chronic rejection, or with morphologic features of AMR. In a sub-group analysis we-identified 9 LTRs who developed early bronchiolitis obliterans syndrome (BOS) in the absence of acute cellular rejection or cytomegalovirus reactivation, but they had significant lung allograft C3d/C4d deposition along with corroborative light-microscopic features suggestive of AMR. Conclusions: Complement activation, as judged by lung allograft deposition of C3d/C4d, is common early post-lung transplant and may be triggered by primary graft dysfunction and/or airway infection, and may play a role in the development of early BOS.