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

IntroductionWhile cystic fibrosis (CF) lung disease is characterized by persistent inflammation and infections and chronic inflammatory diseases are often accompanied by autoimmunity, autoimmune reactivity in CF has not been studied in depth.MethodsIn this work we undertook an unbiased approach to e...

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Main Authors: Ruchi Yadav, Quan-Zhen Li, Hanwen Huang, S. Louis Bridges, J. Michelle Kahlenberg, Arlene A. Stecenko, Balázs Rada
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-09-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1151422/full
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author Ruchi Yadav
Quan-Zhen Li
Hanwen Huang
S. Louis Bridges
J. Michelle Kahlenberg
Arlene A. Stecenko
Balázs Rada
author_facet Ruchi Yadav
Quan-Zhen Li
Hanwen Huang
S. Louis Bridges
J. Michelle Kahlenberg
Arlene A. Stecenko
Balázs Rada
author_sort Ruchi Yadav
collection DOAJ
description IntroductionWhile cystic fibrosis (CF) lung disease is characterized by persistent inflammation and infections and chronic inflammatory diseases are often accompanied by autoimmunity, autoimmune reactivity in CF has not been studied in depth.MethodsIn this work we undertook an unbiased approach to explore the systemic autoantibody repertoire in CF using autoantibody microarrays.Results and discussionOur 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 people with CF 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 associate 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 associate with P. aeruginosa airway infection. In summary, we have identified several new autoantibodies and associations of autoantibody signatures with specific clinical features in CF.
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spelling doaj.art-0786abdff9e54abbba1b6e68cd82499e2023-09-11T11:35:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.11514221151422Cystic fibrosis autoantibody signatures associate with Staphylococcus aureus lung infection or cystic fibrosis-related diabetesRuchi Yadav0Quan-Zhen Li1Hanwen Huang2S. Louis Bridges3J. Michelle Kahlenberg4Arlene A. Stecenko5Balázs Rada6Department of Infectious Diseases, College of Veterinary Medicine, The University of Georgia, Athens, GA, United StatesDepartment of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Epidemiology & Biostatistics, College of Public Health, The University of Georgia, Athens, GA, United StatesDepartment of Medicine, Hospital for Special Surgery, Division of Rheumatology, Weill Cornell Medical College, New York, NY, United StatesDivision of Rheumatology, University of Michigan, School of Medicine, Ann Arbor, MI, United StatesDivision of Pulmonology, Asthma, Cystic Fibrosis and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United StatesDepartment of Infectious Diseases, College of Veterinary Medicine, The University of Georgia, Athens, GA, United StatesIntroductionWhile cystic fibrosis (CF) lung disease is characterized by persistent inflammation and infections and chronic inflammatory diseases are often accompanied by autoimmunity, autoimmune reactivity in CF has not been studied in depth.MethodsIn this work we undertook an unbiased approach to explore the systemic autoantibody repertoire in CF using autoantibody microarrays.Results and discussionOur 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 people with CF 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 associate 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 associate with P. aeruginosa airway infection. In summary, we have identified several new autoantibodies and associations of autoantibody signatures with specific clinical features in CF.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1151422/fullCFRDCF-related diabetescystic fibrosisautoimmunityautoantibody signatureStaphylococcus aureus
spellingShingle Ruchi Yadav
Quan-Zhen Li
Hanwen Huang
S. Louis Bridges
J. Michelle Kahlenberg
Arlene A. Stecenko
Balázs Rada
Cystic fibrosis autoantibody signatures associate with Staphylococcus aureus lung infection or cystic fibrosis-related diabetes
Frontiers in Immunology
CFRD
CF-related diabetes
cystic fibrosis
autoimmunity
autoantibody signature
Staphylococcus aureus
title Cystic fibrosis autoantibody signatures associate with Staphylococcus aureus lung infection or cystic fibrosis-related diabetes
title_full Cystic fibrosis autoantibody signatures associate with Staphylococcus aureus lung infection or cystic fibrosis-related diabetes
title_fullStr Cystic fibrosis autoantibody signatures associate with Staphylococcus aureus lung infection or cystic fibrosis-related diabetes
title_full_unstemmed Cystic fibrosis autoantibody signatures associate with Staphylococcus aureus lung infection or cystic fibrosis-related diabetes
title_short Cystic fibrosis autoantibody signatures associate with Staphylococcus aureus lung infection or cystic fibrosis-related diabetes
title_sort cystic fibrosis autoantibody signatures associate with staphylococcus aureus lung infection or cystic fibrosis related diabetes
topic CFRD
CF-related diabetes
cystic fibrosis
autoimmunity
autoantibody signature
Staphylococcus aureus
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1151422/full
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