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

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease which primarily involves joints and has an incidence of 0.5–1%, making it one of the most prevalent chronic inflammatory diseases.

Even though mechanisms of the disease development are yet to be completely identified, antibodies are known to be important players in that process and connected with the disease severity.

Autoantibodies against citrullinated peptides (ACPAs) and immunoglobulin G (IgG) are particularly important in the diagnostics of RA. An early diagnosis is central to the treatment of RA, as starting a therapy as soon as possible can prevent or halt joint damage in many patients.

Researchers 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 analyze 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).


Results of our study are in accordance with the previous studies that reported decreased galactosylation in RA. The decrease in galactosylation and sialylation in RA has been known for a long time and was observed in multiple independent studies.

The decrease in IgG galactosylation has been regularly associated with RA, while changes in sialylation were reported to be independent of galactosylation and the decrease in sialylation was far less reported.

It is known that both anti-inflammatory and pro-inflammatory activities of IgG are determined by which Fcγ receptor they preferentially bind to and that the receptor affinity depends on the composition of the glycan linked to the 297 asparagine.

IgG carrying G0 glycans has increased affinity to FcγRIII, an activating FcR, and the serum leptin mannose-binding protein. Moreover, besides the classical and lectin pathways of complement activation, IgG bearing G0 is able to activate an alternative complement pathway.

Such G0-bearing IgGs are thus uniquely capable of setting autoimmunity. To the contrary, higher sialylation of IgG decreases its affinity for FcγRIII and increases the expression of FcγRIIB, an inhibitory FcR.

In conclusion, in this study, we showed that IgG N-glycosylation correlates with RA years before RA diagnosis and indicates an active involvement of N-glycans in the disease pathology.

Moreover, these early changes of IgG N-glycome may thus be useful in constructing a sensitive and specific test for early RA diagnosis, needed to enable prompt treatment and prevent irreversible joint destruction as well as to evaluate disease progression, remission, and proper treatment.