Pulmonary alveolar proteinosis: An autoimmune disease lacking an HLA association

Abstract

Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of pulmonary surfactant in alveolar macrophages and alveoli, resulting in respiratory impairment and an increased risk of opportunistic infections. Autoimmune PAP is an autoimmune lung disease that is caused by autoantibodies directed against granulocyte-macrophage colony-stimulating factor (GM-CSF). A shared feature among many autoimmune diseases is a distinct genetic association to HLA alleles. In the present study, we HLA-typed patients with autoimmune PAP to determine if this disease had any HLA association. We analyzed amino acid and allele associations for HLA-A, B, C, DRB1, DQB1, DPB1, DRB3, DRB4 and DRB5 in 41 autoimmune PAP patients compared to 1000 ethnic-matched controls and did not find any HLA association with autoimmune PAP. Collectively, these data may suggest the absence of a genetic association to the HLA in the development of autoimmune PAP.

Fig 1. HEAP limits of detection by patient number.

Identification of significant p-values with known disease associated epitopes by number of patients in the sample. Y-axis shows–Log(p-value) from the epitope analysis, X-axis shows the number of patient samples included in each analysis. For highly significant HLA associations, HEAP can consistently identify association with as few as 20 patients.