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Systems serology in cystic fibrosis: Anti-Pseudomonas IgG1 responses and reduced lung function.
Lu, Shiping; Chen, Kong; Song, Kejing; Pilewski, Joseph M; Gunn, Bronwyn M; Poch, Katie R; Rysavy, Noel M; Vestal, Brian E; Saavedra, Milene T; Kolls, Jay K.
Afiliação
  • Lu S; Department of Immunology and Microbiology, Tulane University, New Orleans, LA, USA; Center for Translational Research in Infection and Inflammation, School of Medicine, Tulane University, New Orleans, LA, USA.
  • Chen K; Division of Pulmonary, Allergy and Critical Care Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • Song K; Center for Translational Research in Infection and Inflammation, School of Medicine, Tulane University, New Orleans, LA, USA.
  • Pilewski JM; Division of Pulmonary, Allergy and Critical Care Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • Gunn BM; Paul G. Allen School of Global Health, Washington State University, Pullman, WA, USA.
  • Poch KR; National Jewish Health, Denver, CO, USA.
  • Rysavy NM; National Jewish Health, Denver, CO, USA.
  • Vestal BE; Center for Genes, Environment and Health, National Jewish Health, Denver, CO, USA.
  • Saavedra MT; National Jewish Health, Denver, CO, USA.
  • Kolls JK; Center for Translational Research in Infection and Inflammation, School of Medicine, Tulane University, New Orleans, LA, USA. Electronic address: jkolls1@tulane.edu.
Cell Rep Med ; 4(10): 101210, 2023 10 17.
Article em En | MEDLINE | ID: mdl-37852181
Nearly one-half of patients with cystic fibrosis (CF) carry the homozygous F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene but exhibit variable lung function phenotypes. How adaptive immunity influences their lung function remains unclear, particularly the serological antibody responses to antigens from mucoid Pseudomonas in sera from patients with CF with varying lung function. Sera from patients with CF with reduced lung function show higher anti-outer membrane protein I (OprI) immunoglobulin G1 (IgG1) titers and greater antibody-mediated complement deposition. Induction of anti-OprI antibody isotypes with complement activity enhances lung inflammation in preclinical mouse models. This enhanced inflammation is absent in immunized Rag2-/- mice and is transferrable to unimmunized mice through sera. In a CF cohort undergoing treatment with elexacaftor-tezacaftor-ivacaftor, the declination in anti-OprI IgG1 titers is associated with lung function improvement and reduced hospitalizations. These findings suggest that antibody responses to specific Pseudomonas aeruginosa (PA) antigens worsen lung function in patients with CF.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fibrose Cística Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fibrose Cística Idioma: En Ano de publicação: 2023 Tipo de documento: Article