TY - JOUR
T1 - Donor-specific antibody characteristics, including persistence and complement-binding capacity, increase risk for chronic lung allograft dysfunction
AU - Iasella, Carlo J.
AU - Ensor, Christopher R.
AU - Marrari, Marilyn
AU - Mangiola, Massimo
AU - Xu, Qingyong
AU - Nolley, Eric
AU - Moore, Cody A.
AU - Morrell, Matthew R.
AU - Pilewski, Joseph M.
AU - Sanchez, Pablo G.
AU - McDyer, John F.
AU - Zeevi, Adriana
N1 - Publisher Copyright:
© 2020 International Society for Heart and Lung Transplantation
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the major complication limiting long-term survival in lung transplant recipients (LTRs), with those developing donor-specific anti–human leukocyte antigen (HLA) antibodies (DSAs) previously found to have increased risk for CLAD. However, as DSA responses vary in timing of development, specificity, breadth, persistence, and complement-binding capacity, we hypothesized that these characteristics would impact CLAD and survival outcomes. METHODS: We retrospectively analyzed DSA characteristics and outcomes in a single-center cohort of 582 LTRs who had serum samples collected prospectively from 2010 to 2016. Luminex-based single antigen bead assays were performed to assess DSA. RESULTS: DSAs were detected in 247 LTRs (42%), of which 124 (21.3%) were de novo DSAs and 53 (9.1%) were complement-binding (C1q+). CLAD developed in 208 LTRs (35.7%) during the follow-up period, with 67.8% determined as bronchiolitis obliterans syndrome phenotype and 32.2% as restrictive allograft syndrome phenotype. We found a shorter time to CLAD in LTRs with persistent DSAs (p = 0.04) and HLA-DQ–specific DSAs (p = 0.03). LTRs who developed C1q+ DSAs had significantly shorter time to CLAD (p < 0.001), with 100% of C1q+ DSAs being persistent and no differences between CLAD phenotypes. CLAD-free survival was significantly reduced in LTRs who developed C1q+ DSAs (p = 0.001), HLA-DQ–specific DSAs (p = 0.03), and multiple DSAs (p = 0.02). CONCLUSIONS: Together, our findings demonstrate that DSA characteristics of persistence, HLA-DQ specificity, and C1q+ DSAs are associated with shorter time to CLAD. Additionally, C1q+, HLA-DQ–specific, and multiple DSAs are associated with decreased CLAD-free survival. These characteristics may improve DSA risk stratification for deleterious outcomes in LTRs.
AB - BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the major complication limiting long-term survival in lung transplant recipients (LTRs), with those developing donor-specific anti–human leukocyte antigen (HLA) antibodies (DSAs) previously found to have increased risk for CLAD. However, as DSA responses vary in timing of development, specificity, breadth, persistence, and complement-binding capacity, we hypothesized that these characteristics would impact CLAD and survival outcomes. METHODS: We retrospectively analyzed DSA characteristics and outcomes in a single-center cohort of 582 LTRs who had serum samples collected prospectively from 2010 to 2016. Luminex-based single antigen bead assays were performed to assess DSA. RESULTS: DSAs were detected in 247 LTRs (42%), of which 124 (21.3%) were de novo DSAs and 53 (9.1%) were complement-binding (C1q+). CLAD developed in 208 LTRs (35.7%) during the follow-up period, with 67.8% determined as bronchiolitis obliterans syndrome phenotype and 32.2% as restrictive allograft syndrome phenotype. We found a shorter time to CLAD in LTRs with persistent DSAs (p = 0.04) and HLA-DQ–specific DSAs (p = 0.03). LTRs who developed C1q+ DSAs had significantly shorter time to CLAD (p < 0.001), with 100% of C1q+ DSAs being persistent and no differences between CLAD phenotypes. CLAD-free survival was significantly reduced in LTRs who developed C1q+ DSAs (p = 0.001), HLA-DQ–specific DSAs (p = 0.03), and multiple DSAs (p = 0.02). CONCLUSIONS: Together, our findings demonstrate that DSA characteristics of persistence, HLA-DQ specificity, and C1q+ DSAs are associated with shorter time to CLAD. Additionally, C1q+, HLA-DQ–specific, and multiple DSAs are associated with decreased CLAD-free survival. These characteristics may improve DSA risk stratification for deleterious outcomes in LTRs.
KW - C1q
KW - chronic lung allograft dysfunction
KW - complement fixing antibodies
KW - donor-specific antibody
KW - lung transplantation
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U2 - 10.1016/j.healun.2020.09.003
DO - 10.1016/j.healun.2020.09.003
M3 - Article
C2 - 32981841
AN - SCOPUS:85091518301
SN - 1053-2498
VL - 39
SP - 1417
EP - 1425
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 12
ER -