Intragraft donor-specific anti-HLA antibodies in phenotypes of chronic lung allograft dysfunction

Circulating anti-human leukocyte antigen (HLA) serum donor-specific antibodies (sDSAs) increase the risk of chronic lung allograft dysfunction (CLAD) and mortality. Discrepancies between serological and pathological/clinical findings are common. Therefore, we aimed to assess the presence of tissue-bound graft DSAs (gDSAs) in CLAD explant tissue compared with sDSAs.

Tissue cores, obtained from explant lungs of unused donors (n=10) and patients with bronchiolitis obliterans syndrome (BOS; n=18) and restrictive allograft syndrome (RAS; n=18), were scanned with micro-computed tomography before elution of antibodies. Total IgG levels were measured via ELISA. Anti-HLA class I and II IgG gDSAs were identified using Luminex single antigen beads and compared with DSAs found in serum samples.

Overall, mean fluorescence intensity was higher in RAS eluates compared with BOS and controls (p<0.0001). In BOS, two patients were sDSA⁺/gDSA⁺ and two patients were sDSA^-/gDSA⁺. In RAS, four patients were sDSA⁺/gDSA⁺, one patient was sDSA⁺/gDSA^- and five patients were sDSA^-/gDSA⁺. Serum and graft results combined, DSAs were more prevalent in RAS compared with BOS (56% versus 22%; p=0.04). There was spatial variability in gDSA detection in one BOS patient and three RAS patients, who were all sDSA^-. Total graft IgG levels were higher in RAS than BOS (p<0.0001) and in gDSA⁺ versus gDSA^- (p=0.0008), but not in sDSA⁺ versus sDSA^- (p=0.33). In RAS, total IgG levels correlated with fibrosis (r= -0.39; p=0.02).

This study underlines the potential of gDSA assessment as complementary information to sDSA findings. The relevance and applications of gDSAs need further investigation.