Donor-specific antibody characteristics, including persistence and complement-binding capacity, increase risk for chronic lung allograft dysfunction

Autor: Marilyn Marrari, Qingyong Xu, Joseph M. Pilewski, John F. McDyer, Eric P. Nolley, Pablo G. Sanchez, Massimo Mangiola, Adriana Zeevi, Cody A. Moore, Carlo J. Iasella, Christopher R. Ensor, Matthew R. Morrell
Rok vydání: 2020
Předmět:
Male
Pulmonary and Respiratory Medicine
medicine.medical_specialty
medicine.medical_treatment
030232 urology & nephrology
Bronchiolitis obliterans
Human leukocyte antigen
030230 surgery
Gastroenterology
Persistence (computer science)
03 medical and health sciences
0302 clinical medicine
HLA Antigens
Isoantibodies
Internal medicine
medicine
Humans
Transplantation
Homologous
Lung transplantation
Bronchiolitis Obliterans
Lung
Retrospective Studies
Transplantation
biology
business.industry
Complement C1q
Donor specific antibodies
Graft Survival
Middle Aged
medicine.disease
Tissue Donors
Transplant Recipients
medicine.anatomical_structure
Chronic Disease
Cohort
biology.protein
Female
Surgery
Primary Graft Dysfunction
Antibody
Cardiology and Cardiovascular Medicine
business
Follow-Up Studies
Lung Transplantation
Zdroj: The Journal of Heart and Lung Transplantation. 39:1417-1425
ISSN: 1053-2498
Popis: 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.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.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 (p0.001), 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).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.
Databáze: OpenAIRE
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