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

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

Author information

1
Leuven Lung Transplant Group, Dept of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium.
2
Laboratoire d'Immunologie et Histocompatibilité, Saint-Louis Hospital, Paris, France.
3
Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross-Flanders, Mechelen, Belgium.
4
Dept of Immunology and Microbiology, KU Leuven, Leuven, Belgium.
5
Dept of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium.
6
Service de Transplantation Pulmonaire, Foch Hospital, Suresnes, France.
7
Leuven Lung Transplant Group, Dept of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium stijn.verleden@kuleuven.be.

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.

Conflict of interest statement

Conflict of interest: A. Sacreas has nothing to disclose. Conflict of interest: J-L. Taupin has nothing to disclose. Conflict of interest: M-P. Emonds has nothing to disclose. Conflict of interest: L. Daniëls has nothing to disclose. Conflict of interest: D.E. Van Raemdonck has nothing to disclose. Conflict of interest: R. Vos has nothing to disclose. Conflict of interest: G.M. Verleden has nothing to disclose. Conflict of interest: B.M. Vanaudenaerde has nothing to disclose. Conflict of interest: A. Roux reports personal fees and nonfinancial support from Biotest, personal fees from Thermo Fisher, nonfinancial support from CSL Berhing, outside the submitted work. Conflict of interest: S.E. Verleden has nothing to disclose.

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