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Biochim Biophys Acta Mol Basis Dis. 2018 Jun;1864(6 Pt A):2034-2039. doi: 10.1016/j.bbadis.2018.03.018. Epub 2018 Mar 20.

Low galactosylation of IgG associates with higher risk for future diagnosis of rheumatoid arthritis during 10 years of follow-up.

Author information

1
Genos Glycoscience Research Laboratory, Zagreb, Croatia.
2
National Institute for Health and Welfare, Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
3
Genos Glycoscience Research Laboratory, Zagreb, Croatia; St. Catherine Specialty Hospital, Zabok, Zagreb, Croatia; JJ Strossmayer University of Osijek, School of Medicine, Osijek, Croatia; University of Split, School of Medicine, Split, Croatia; Eberly College of Science, The Pennsylvania State University, University Park, PA, USA; Children's Hospital Srebrnjak, Zagreb, Croatia.
4
National Institute for Health and Welfare, Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland; Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland; University of Tartu, Estonian Genome Center, Tartu, Estonia.
5
Genos Glycoscience Research Laboratory, Zagreb, Croatia; University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia. Electronic address: glauc@pharma.hr.

Abstract

Antibodies are known to have an important role in the development of rheumatoid arthritis (RA), one of the most prevalent chronic inflammatory diseases which primarily involves the joints. Most RA patients develop autoantibodies against immunoglobulin G (IgG) and changes in IgG glycosylation have been associated with RA. We undertook this study to determine whether altered IgG glycosylation precedes the disease diagnosis. We studied IgG glycosylation in RA in two prospective cohorts (N = 14,749) by measuring 28 IgG glycan traits in 179 subjects who developed RA within 10-years follow-up and 358 matched controls. Ultra-performance liquid chromatography method based on hydrophilic interactions (HILIC-UPLC) was used to analyse IgG glycans. Future RA diagnosis associated with traits related to lower galactosylation and sialylation of IgG when comparing the cases to the matched controls. In RA cases, these traits did not correlate with the time between being recruited to the study and being diagnosed with RA (median time 4.31 years). The difference in IgG glycosylation was relatively stable and present years before diagnosis. This indicates that long-acting factors affecting IgG glycome composition are among the underlying mechanisms of RA and that decreased galactosylation is a pre-existing risk factor involved in the disease development.

KEYWORDS:

Biomarker; Immunoglobulin G; N-glycans; Rheumatoid arthritis; Risk factor

PMID:
29572115
DOI:
10.1016/j.bbadis.2018.03.018
[Indexed for MEDLINE]
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