Profiling effector and regulatory T cell populations in the peripheral blood and lung tissue of lung transplant patients to identify markers of rejection and toleranc
Examining the role of B cell dependent immune aggregates in driving local inflammation and their association with CLAD progression
Multicolour antibody detection (blue = IgA, green = IgG, red = IgM)
Investigating humeral autoimmunity mechanisms, including the role of donor-specific antibodies and biomarkers predictive of CLAD
Longitudinal dynamics of a specific autoantibody of interest that is associated with future CLAD
Antibodies are precision weapons, naturally selected to target and eliminate foreign pathogens. Following lung transplantation, the recipient's immune system mounts an antibody response against donor MHC molecules – a consequence of HLA polymorphism – resulting in donor-specific antibodies (DSAs). While DSAs are the most notorious humoral challenge post-transplant, the role of autoantibodies targeting self-antigens in CLAD has only recently gained attention, reflecting a profound breakdown in self-tolerance.
Despite this, the diversity of autoantibodies, particularly those directed against lung-specific self-antigens, remains poorly understood. To address this, our lab developed a novel three-color antigen microarray capable of detecting hundreds of antibody specificities across multiple isotypes in both blood and airways. Using this platform, we identified novel lung-specific autoantibodies that form a minimally invasive combinatorial serum signature, detectable before or shortly after transplantation, and strongly predictive of future CLAD. This work, now patent-protected, is undergoing further validation as a prognostic biomarker for CLAD, with ongoing studies to assess its generalizability.
We also demonstrated that patients with both lung-specific autoantibodies and DSAs face a significantly higher risk of CLAD compared to those with either feature alone, suggesting a potential tissue-specific mechanistic pathway underlying CLAD. The central question remains whether these autoantibodies directly contribute to allograft injury or merely reflect an epiphenomenon of other injurious processes and associated tissue damage. To address this, we are pursuing methods to facilitate deeper phenotypic insights into specific autoantibodies and developing experimental systems to directly test the mechanistic roles of candidate autoantibodies identified through our analyses.
Publications:
Vosoughi et. al. Humoral immunity to lung antigens early post-transplant confers risk for chronic lung allograft dysfunction. Under Review, Journal of Heart and Lung Transplantation.
Conference Abstract: A Serum Autoantibody (AAB) Signature is Associated with Future CLAD. Vosoughi et al. JHLT 2024;43(4)pp. S32-S33 https://doi.org/10.1016/j.healun.2024.02.064