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

Eur Respir J. 2019 Nov 7;54(5):1900847. doi: 10.1183/13993003.00847-2019. Print 2019 Nov.

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allografts / immunology
  • Allografts / physiopathology*
  • Antibodies / blood*
  • Bronchiolitis Obliterans / immunology
  • Chronic Disease
  • Female
  • HLA Antigens / immunology*
  • Humans
  • Lung Diseases / surgery*
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Phenotype
  • Postoperative Complications / genetics
  • Postoperative Complications / immunology*
  • Retrospective Studies
  • Tissue Donors
  • Young Adult

Substances

  • Antibodies
  • HLA Antigens