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Title
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Intragraft donor-specific anti-HLA antibodies in phenotypes of chronic lung allograft dysfunction
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Author
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Institution/Organisation
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Leuven Lung Transplant Grp
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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The European respiratory journal / European Respiratory Society [Lausanne] - Copenhagen, 1988, currens
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Publication
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Copenhagen
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2019
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ISSN
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0903-1936
[print]
1399-3003
[online]
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DOI
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10.1183/13993003.00847-2019
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Volume/pages
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54
:5
(2019)
, 10 p.
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Article Reference
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1900847
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ISI
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000496132300007
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Pubmed ID
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31439680
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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