Cystic fibrosis autoantibody signatures associate with Staphylococcus aureus lung infection or cystic fibrosis-related diabetes

While cystic fibrosis (CF) lung disease is characterized by persistent
inflammation and infections, and chronic inflammatory diseases are often
accompanied by autoimmunity, autooimmune reactivity in CF has not been
studied in depth. In this work, we undertook an unbiased approach to
explore the systemic autoantibody repertoire in CF. Our results show
higher levels of several new autoantibodies in the blood of people with CF
(PwCF) compared to control subjects. Some of these are IgA autoantibodies
targeting neutrophil components or autoantigens linked to
neutrophil-mediated tissue damage in CF. We also found that PwCF with
higher systemic IgM autoantibody levels have lower prevalence of S. aureus
infection. On the other hand, IgM autoantibody levels in S.
aureus-infected PwCF correlate with lung disease severity. Diabetic PwCF
have significantly higher levels of IgA autoantibodies in their
circulation compared to nondiabetic PwCF, and several of their IgM
autoantibodies are associated with worse lung disease. In contrast, in
nondiabetic PwCF blood levels of IgA autoantibodies correlate with lung
disease. We have also identified other autoantibodies in CF that are
associated with P. aeruginosa airway infection. In summary, we have
identified several new autoantibodies and associations of autoantibody
signatures with specific clinical features in CF.