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

Antibodies to HLA are a major cause of chronic lung allograft dysfunction (CLAD) following lung transplantation (LTx), however mounting evidence indicates non-HLA autoantibodies may also play a role. LTx recipients may have increased autoantibodies related to their native disease, and these may impact both pre-transplant assays and LTx outcomes. The flow cytometry crossmatch (FXM) assay is often used peri-LTx to define immunological risk; however, the presence of autoantibodies in LTx recipients may associate with positivity in the FXM, and the clinical impact of this is unknown. In a retrospective, single-center cohort, we investigate the association of pre-transplant non-HLA autoantibodies on the FXM and subsequent CLAD. The serum of 68 LTx recipients was retrospectively tested for 39 autoantibody targets pre- and 12-months post-transplant. A further cohort of waitlisted LTx recipients (n = 25) with HLA antibody-negative FXM-positive sera was evaluated for the presence of these same 39 autoantibodies to determine the association of autoantibodies and FXM reactivity. CLAD status and freedom from CLAD were defined and analysed for all recipients. MFI strengths in five autoantibody targets associated with FXM positivity when compared to the HLA donor-specific and FXM negative patients. LTx recipients who were positive to ≥ 8 non-HLA autoantibodies had an increased risk of CLAD (HR = 3.09 p < 0.01) and a decreased freedom from CLAD (p < 0.01). Recipients with increased positivity to non-HLA autoantibodies pre-LTx demonstrate increased risk of CLAD and decreased freedom from CLAD. Furthermore, the strength of these autoantibodies is associated with FXM positivity in the absence of HLA antibodies. Further research with larger cohorts is required to better understand which autoantibody targets are responsible for CLAD outcomes, and to define best cut-offs to define reactivity.