Abstract
Characterising chronic lung diseases is challenging. New, less invasive diagnostics are needed to decipher disease pathologies and subphenotypes. Fc galactosylation is known to affect IgG function, and is altered in autoimmune disorders and under other pathological conditions. We tested how well Fc glycans in IgG from bronchoalveolar lavage fluid (BALF) and serum correlated, and if the Fc glycan profile could reveal pulmonary inflammation.
A shotgun proteomics approach was used to profile Fc glycans in serum and BALF of controls (n=12) and sarcoidosis phenotypes (Löfgren's syndrome (LS), n=11; and non-LS, n=12). Results were further validated in severe asthma (SA) (n=20) and published rheumatoid arthritis (RA) patient data (n=13) including clinical information.
Intra-individually, Fc-galactosylation status of IgG1 (R2=0.87) and IgG4 (R2=0.95) correlated well between matrixes. Following GlycoAge-index correction, the ratio between agalactosylated and digalactosylated Fc glycans of IgG4 could distinguish sarcoidosis and SA from healthy and RA subjects with a mean±se area under the curve (AUC) of 78±6%. The AUC increased to 83±6% using the more chronic lung disease types (non-LS and SA) and most strikingly, to 87±6% for the SA subgroup.
The results indicate that the Fc galactosylation status of IgG4 is a potential blood test marker for chronic lung inflammation.
Abstract
IgG4 Fc galactosylation correlates between serum and BALF (R2=0.95) and is a potential blood marker for chronic lung inflammation http://ow.ly/XaNd30k35wg
Footnotes
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Author contributions: J. Grunewald, R.A. Zubarev, T. Heyder, E. Wiklundh and S.L. Lundström designed the study; E. Wiklundh characterised the sarcoid, and A. James and S-E. Dahlén the asthma subjects; A. Eklund performed bronchoscopies and generated clinical data; J. Grunewald, S-E. Dahlén and R.A. Zubarev provided financial support and essential infrastructure; T. Heyder, E. Wiklundh and S.L. Lundström performed IgG purifications; S.L. Lundström performed mass spectrometric analysis; T. Heyder, E. Wiklundh, A. James and S.L. Lundström performed data analyses; and T. Heyder, E. Wiklundh and S.L. Lundström interpreted the data and drafted the manuscript. All authors read, edited and commented on the manuscript.
BIOAIR study group: Mina Gaga (University of Athens, Athens, Greece), Nikos M. Siafakas (University of Crete, Heraklion, Greece), Alberto Papi (University of Ferrara, Ferrara, Italy), Leonardo M. Fabbri (University of Modena, Modena, Italy), Guy Joos (University of Ghent, Ghent, Belgium), Klaus F. Rabe (The Christian Albrechts University, Kiel, Germany), Peter Sterk (Amsterdam Medical Centre, Amsterdam, The Netherlands), Elisabeth H. Bel (Amsterdam Medical Centre, Amsterdam, The Netherlands), Sebastian L. Johnston (The Imperial College of Science and Technology, London, UK), Pascal Chanez (University of Marseilles, Marseilles, France), Mark Gjormarkaj (Italian Research Council, Palermo, Italy), Peter H. Howarth (University of Southampton, Southampton, UK), Ewa Niżankowska-Mogilnicka (The Jagellonian University, Krakow, Poland) and Roelinde Middelveld (Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden).
Conflict of interest: S-E. Dahlén reports receiving personal fees from AstraZeneca, GlaxoSmithKline, Novartis, Merck, RSPR Pharma, Regeneron and Teva for service on scientific advisory boards, outside the submitted work.
Support statement: This study was supported by The Swedish Heart Lung Foundation; The Swedish Research Council; King Gustaf V's and Queen Victoria's Freemasons' Foundation; The Stockholm County Council; The Center for Inflammatory Diseases; the ChAMP (Centre for Allergy Research Highlights Asthma Markers of Phenotype) consortium, which is funded by the Swedish Foundation for Strategic Research, Karolinska Institutet, the AstraZeneca and Science for Life Laboratory Joint Research Collaboration, and the Vårdal Foundation; and Karolinska Institutet. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received February 19, 2018.
- Accepted April 27, 2018.
- Copyright ©ERS 2018
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.