PURPOSE:Antibody-mediated rejection (AMR) may be associated with allograft dysfunction and loss in lung transplant recipients (LTR). Detection and management of AMR is hampered by the lack of standardized diagnostic criteria. The purpose of the study was to examine markers indicative of AMR including graft dysfunction, donor specific antibodies (DSA), histology and C4d staining to determine the optimal combination to use for the diagnosis of AMR.
METHODS:This was a retrospective analysis of 17 LTR at our center who underwent transbronchial biopsies (TBBX) for clinical, radiographic and/or spirometric deterioration, and who had complete immunopathologic data available. A sensitive single antigen microarray technique was utilized to detect DSA on serum before transplant and at time of TBBX. Biopsies were reviewed for histologic abnormalities and C4d staining on frozen sections.
RESULTS:No significant differences in demographics, immunosuppression, change in FEV1, CMV status, ischemic time, reperfusion injury or time to TBBX were found between patients with or without DSA. DSA was positive (+) in 5/17 LTR; of these, three (1 case HLA-A2; 2 cases HLA-DR53) also showed diffuse C4d staining along septal walls with a spectrum of histologic findings consistent with AMR: intra-alveolar fibrin, fibrin thrombi, septal wall fibrin and/or neutrophils. The other two with DSA+ (both with HLA-DQ7) were C4d negative; both had obliterative bronchiolitis while one also had histology suggestive of AMR. The remaining 12 LTR had no detectable DSA, or C4d. Of these, ten had infection only and 2 had infection and acute cellular rejection (ACR).
CONCLUSION:Clinical deterioration related to AMR was observed in LTR with positive DSA. A decline in clinical status in DSA-, C4d- patients was due to etiologies other then AMR (infection and/or ACR). The combination of DSA, histology and C4d analysis provides a promising approach for detecting the presence of AMR.
CLINICAL IMPLICATIONS:Prospective studies are warranted to determine when and how best to utilize these markers to create a standardized set of criteria for the detection and diagnosis of AMR.
DISCLOSURE:Deborah Levine, None.