Elevated IgG4 serum levels in patients with cystic fibrosis.

Abdelwahab Omri,Axelle Clerc,Stéphane Durupt,Isabelle Durieu,Raphaële Nové-Josserand,Colette Chapuis-Cellier,Quitterie Reynaud,Jean Christophe Lega

doi:10.1371/journal.pone.0181888

Abstract

ObjectiveSerum immunoglobulin (Ig) G4 elevation has been associated with several pathological conditions other than IgG4-related disease (IgG4-RD). In cystic fibrosis (CF), an elevation of specific IgG4 has been associated with colonization and infection by Pseudomonas aeruginosa. IgG4 elevation may be a marker of chronic infection or inflammatory stimulation. The aim of this study was to explore the prevalence of elevated IgG4 levels in CF and its correlation with the major clinical and microbiological features found in CF patients.MethodsIn a cross-sectional study, we analyzed data from a large cohort of adult CF patients attending the CF center of Lyon University Hospital. An elevated IgG4 level was defined as being above the cut-off value of 135 mg/dL.ResultsOne hundred and sixty-five CF patients were analyzed. An IgG4 elevation was detected in 43 patients (26%). Compared with the control group (≤ 135 mg/dL), high IgG4 patients exhibited a greater prevalence of Staphylococcus aureus colonization and higher IgG, IgG1, IgG2 and IgE levels. No significant differences were observed in terms of pulmonary function, colonization with Pseudomonas aeruginosa, or the annual rate of bronchial exacerbations.ConclusionAn elevated IgG4 serum level was frequently detected in adult CF patients and did not appear to be associated with poor lung function. We suggest that IgG4 elevation is a marker of the activation of tolerance. Its clinical significance remains to be demonstrated.

Highlights

Cystic fibrosis (CF) is the most common severe autosomal recessive genetic disease in Europe
An elevated IgG4 serum level was frequently detected in adult CF patients and did not appear to be associated with poor lung function
We suggest that IgG4 elevation is a marker of the activation of tolerance

Summary

Introduction

Cystic fibrosis (CF) is the most common severe autosomal recessive genetic disease in Europe. The disease is caused by a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator protein, a chloride ion channel whose abnormal function leads to the hyperviscosity of exocrine secretions and obstructive damage to many organs, including the lung, pancreas, hepatobiliary tracts, and vas deferens [1]. Immunoglobulin (Ig) G4 is a unique antibody in both structure and function. This molecule accounts for less than 5% of the total IgG in healthy persons and is the least abundant IgG subclass. Unlike other IgG subclasses, IgG4 is unable to fix complement or precipitate antigens [2,3]. Despite its traditional role as an antiinflammatory immunoglobulin, IgG4 is presumed to play a central role in certain immunemediated conditions

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