RT Journal Article
SR Electronic
T1 Intragraft donor-specific anti-HLA antibodies in phenotypes of chronic lung allograft dysfunction
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1900847
DO 10.1183/13993003.00847-2019
VO 54
IS 5
A1 Annelore Sacreas
A1 Jean-Luc Taupin
A1 Marie-Paule Emonds
A1 Liesbeth Daniëls
A1 Dirk E. Van Raemdonck
A1 Robin Vos
A1 Geert M. Verleden
A1 Bart M. Vanaudenaerde
A1 Antoine Roux
A1 Stijn E. Verleden
A1 ,
YR 2019
UL http://erj.ersjournals.com/content/54/5/1900847.abstract
AB 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.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