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.
Abstract
Discrepancies between serological and pathological/clinical findings in DSAs after lung transplantation are common. This article provides evidence that graft DSA assessment yields complementary information for lung transplant patients. http://bit.ly/2GIkae1
Footnotes
The Leuven Lung Transplant Group includes: Anke Van Herck, Janne Kaes, Tobias Heigl, Sofie Ordies, Laurens J. De Sadeleer, Arno Vanstapel, Arne P. Neyrinck, Veronique Schaevers, Lieven J. Dupont, Jonas Yserbyt, Laurent Godinas, Lieven Depypere, Anna E. Frick, Laurens J. Ceulemans, Eric K. Verbeken, Birgit Weynand, Paul De Leyn, Willy Coosemans, Hans Van Veer, Philippe Nafteux and Herbert Decaluwé.
Support statement: R. Vos is senior clinical research fellow of the Research Foundation Flanders (FWO), Belgium (12G8715N) and is supported by a research grant of UZ Leuven, Belgium (STG15/023). S.E. Verleden is a post-doctoral research fellow of the Research Foundation Flanders (FWO 12G8715N and 1500617N), Belgium and is supported by a research grant from the International Society for Heart and Lung Transplantation and the KU Leuven (C24/18/073)
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.
- Received April 29, 2019.
- Accepted July 31, 2019.
- Copyright ©ERS 2019