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Donor-specific antibody characteristics, including persistence and complement-binding capacity, increase risk for

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Donor-specific antibody (DSA) characteristics like persistence, HLA-DQ specificity, and complement-binding capacity significantly impact chronic lung allograft dysfunction (CLAD) and survival in lung transplant recipients (LTRs). These factors can help predict adverse outcomes.

Keywords:
C1qchronic lung allograft dysfunctioncomplement fixing antibodiesdonor-specific antibodylung transplantation

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Area of Science:

  • Transplantation immunology
  • Allograft rejection
  • Immunogenetics

Background:

  • Chronic lung allograft dysfunction (CLAD) is a primary cause of mortality in lung transplant recipients (LTRs).
  • Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) are linked to increased CLAD risk.
  • The specific characteristics of DSA responses may influence CLAD development and patient survival.

Purpose of the Study:

  • To investigate the impact of DSA characteristics on CLAD development and survival outcomes in LTRs.
  • To determine if DSA specificity, persistence, and complement-binding capacity affect CLAD risk and prognosis.

Main Methods:

  • Retrospective analysis of a single-center cohort of 582 LTRs with prospectively collected serum samples (2010-2016).
  • Luminex-based single antigen bead assays were utilized to detect and characterize DSAs.
  • Outcomes including CLAD development, phenotype, and survival were assessed in relation to DSA characteristics.

Main Results:

  • Donor-specific antibodies (DSAs) were detected in 42% of LTRs; 9.1% were complement-binding (C1q+).
  • Persistent DSAs and HLA-DQ-specific DSAs were associated with a shorter time to CLAD (p=0.04 and p=0.03, respectively).
  • Complement-binding (C1q+) DSAs significantly reduced time to CLAD (p < 0.001) and CLAD-free survival (p=0.001).

Conclusions:

  • DSA characteristics such as persistence, HLA-DQ specificity, and C1q+ status are critical determinants of CLAD development and progression.
  • C1q+, HLA-DQ-specific, and multiple DSAs are associated with reduced CLAD-free survival.
  • Characterizing DSAs based on these features can improve risk stratification for adverse outcomes in lung transplant recipients.