BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease

Area of Science:

• Immunology
• Pulmonology
• Genetics

Background:

• Interstitial lung disease (ILD) is a complex disorder often linked to autoimmune conditions.
• The role of lung-specific autoimmune responses in ILD pathogenesis remains unclear.

Purpose of the Study:

• To investigate the link between autoimmunity targeting lung-specific proteins and ILD.
• To determine if BPIFB1 autoantibodies are associated with ILD in autoimmune polyglandular syndrome type 1 (APS1) and other ILD forms.

Main Methods:

• Screening of APS1 patients and other ILD cohorts for BPIFB1 autoantibodies.
• Analysis of an animal model (Aire⁻/⁻ mice) for ILD and autoantibodies.
• Investigation of thymic tolerance defects in autoantibody production.

Main Results:

• BPIFB1 autoantibodies were found in 100% of APS1 patients with ILD and in subsets of non-APS1 ILD patients.
• Autoantibodies to a similar lung antigen (BPIFB9) were present in an APS1 animal model and correlated with ILD.
• Thymic tolerance defects contributed to autoantibody production and ILD in the animal model.

Conclusions:

• Autoimmunity targeting the lung-specific antigen BPIFB1 may drive ILD in APS1 and other ILD subsets.
• Lung-specific autoimmunity plays a role in the development of ILD.
• BPIFB1 autoantibodies serve as potential biomarkers for ILD in specific patient groups.