Non-HLA Autoantibodies Associate With a Positive Flow-Crossmatch Pre- and Chronic Lung Allograft Dysfunction Post-...

Area of Science:

• Immunology
• Transplantation Science
• Clinical Medicine

Background:

• Antibodies to Human Leukocyte Antigens (HLA) are a primary cause of chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx).
• Emerging evidence suggests non-HLA autoantibodies may also contribute to CLAD, potentially impacting pre-transplant assessments and LTx outcomes.
• The flow cytometry crossmatch (FXM) assay is used to assess immunological risk, but the influence of autoantibodies on FXM results and their clinical significance in LTx recipients is unclear.

Purpose of the Study:

• To investigate the association between pre-transplant non-HLA autoantibodies, FXM positivity, and the development of CLAD in lung transplant recipients.
• To determine if the presence and strength of non-HLA autoantibodies correlate with FXM reactivity in the absence of HLA antibodies.
• To analyze the impact of non-HLA autoantibody positivity on CLAD status and freedom from CLAD post-LTx.

Main Methods:

• A retrospective, single-center cohort study involving 68 lung transplant recipients.
• Serum samples were tested for 39 autoantibody targets pre- and 12-months post-transplant.
• A separate cohort of 25 waitlisted recipients with HLA antibody-negative, FXM-positive sera was evaluated for non-HLA autoantibodies to assess FXM association.

Main Results:

• The median fluorescence intensity (MFI) of five autoantibody targets was associated with FXM positivity compared to HLA donor-specific and FXM-negative patients.
• Lung transplant recipients positive for ≥8 non-HLA autoantibodies showed a significantly increased risk of CLAD (HR=3.09, p<0.01) and decreased freedom from CLAD (p<0.01).
• Increased non-HLA autoantibody positivity pre-LTx was linked to higher CLAD risk and reduced freedom from CLAD, with autoantibody strength correlating with FXM positivity.

Conclusions:

• Pre-transplant positivity for non-HLA autoantibodies is associated with an increased risk of CLAD and reduced freedom from CLAD after lung transplantation.
• The strength of non-HLA autoantibodies correlates with FXM positivity, even when HLA antibodies are absent, suggesting a role in immunological risk assessment.
• Further research with larger cohorts is necessary to identify specific autoantibody targets responsible for CLAD and establish optimal reactivity cut-offs.