Background: The diagnosis of pulmonary antibody–mediated rejection (AMR) remains challenging with lack of specific defining features. This study evaluated the diagnostic and prognostic significance of intragraft anti human leukocyte antigen (HLA) donor–specific antibodies (gDSA) in pulmonary AMR. Methods: This multicenter prospective study enrolled adult lung transplant recipients (LTR) with serum anti-HLA DSA (sDSA) >1,000 Luminex mean fluorescence intensity (MFI). Transbronchial biopsies (TBBx) were obtained for both standard histologic analysis and cryopreservation to detect anti-HLA class I and II gDSA, using Luminex single-antigen beads assay. Clinical follow-up was conducted over 24 months. An expert pathologist reviewed all TBBx using a predefined checklist. A blinded adjudication panel categorized clinical diagnoses as possible, probable, or definite AMR and non-AMR conditions. The primary objective was to assess gDSA sensitivity and specificity for AMR diagnosis. Additionally, we compared graft outcomes between gDSA+ vs gDSA− patients. Results: Seventy-seven LTR from 5 centers were included from August 2019 to July 2022. Twenty-nine patients were classified as probable or definite clinical/subclinical AMR. Among the cohort, 13 had positive gDSA. gDSA sensitivity, specificity, and positive predictive value for AMR diagnosis were 34.4%, 93.7%, and 76.9%, respectively. gDSA diagnostic performance for AMR was better than sDSA ≥12,500 MFI (sensitivity 37.9%, specificity 85.4%, and positive predictive value 61.1%). Event-free survival analysis (10% forced expiratory volume in 1 second decline or graft loss) showed no significant differences by gDSA positivity. Limited biopsy sampling and spatial heterogeneity may have biased sensitivity and prognostic performances of the technique. Conclusions: gDSA might offer a specific complementary support for the clinical diagnosis of AMR following lung transplantation.
Diagnostic significance of intragraft donor-specific anti-HLA antibodies in pulmonary antibody-mediated rejection
Pezzuto, Federica;Calabrese, Fiorella
2025
Abstract
Background: The diagnosis of pulmonary antibody–mediated rejection (AMR) remains challenging with lack of specific defining features. This study evaluated the diagnostic and prognostic significance of intragraft anti human leukocyte antigen (HLA) donor–specific antibodies (gDSA) in pulmonary AMR. Methods: This multicenter prospective study enrolled adult lung transplant recipients (LTR) with serum anti-HLA DSA (sDSA) >1,000 Luminex mean fluorescence intensity (MFI). Transbronchial biopsies (TBBx) were obtained for both standard histologic analysis and cryopreservation to detect anti-HLA class I and II gDSA, using Luminex single-antigen beads assay. Clinical follow-up was conducted over 24 months. An expert pathologist reviewed all TBBx using a predefined checklist. A blinded adjudication panel categorized clinical diagnoses as possible, probable, or definite AMR and non-AMR conditions. The primary objective was to assess gDSA sensitivity and specificity for AMR diagnosis. Additionally, we compared graft outcomes between gDSA+ vs gDSA− patients. Results: Seventy-seven LTR from 5 centers were included from August 2019 to July 2022. Twenty-nine patients were classified as probable or definite clinical/subclinical AMR. Among the cohort, 13 had positive gDSA. gDSA sensitivity, specificity, and positive predictive value for AMR diagnosis were 34.4%, 93.7%, and 76.9%, respectively. gDSA diagnostic performance for AMR was better than sDSA ≥12,500 MFI (sensitivity 37.9%, specificity 85.4%, and positive predictive value 61.1%). Event-free survival analysis (10% forced expiratory volume in 1 second decline or graft loss) showed no significant differences by gDSA positivity. Limited biopsy sampling and spatial heterogeneity may have biased sensitivity and prognostic performances of the technique. Conclusions: gDSA might offer a specific complementary support for the clinical diagnosis of AMR following lung transplantation.
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