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

Author ORCID

Rada Balazs 0000-0002-9742-4955

Publication Date

8-30-2023

Abstract

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.

Keywords

Cystic fibrosis, Autoimmunity, autoantibody signature, Staphylococcus aureus, CF-related diabetes

Related Publication URL

https://doi.org/10.3389/fimmu.2023.1151422

Repository

Dryad

Repository Identifier

114762

Funder

National Heart Lung and Blood Institute

National Institute of Allergy and Infectious Diseases

Funder ROR

https://ror.org/012pb6c26

https://ror.org/043z4tv69

Grant Number

R01HL136707

R21AI154343

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