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Abstract

Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA.

Two mechanisms of the enhanced antibody-dependent cellular cytotoxicity (ADCC) efficacy of non-fucosylated therapeutic antibodies in human blood

“…Human sera from 12 healthy individuals were employed; the individual sera themselves were confirmed not to show any detectable cytotoxic activity against human B cells in this experiment. Although the 12 individual sera displayed slight differences in terms of IgG1 concentration (5.3 to 7.5 mg/mL) and the relative amount of non-fucosylated Fc oligosaccharides (1.2 to 6.5%), consistent with previous reports [30,31], the intensity of inhibitory activity of individual serum against the ADCC of fucosylated anti-CD20 did not significantly correlate with these differences.…”

Tertiary Lymphoid Structures: Autoimmunity Goes Local

“…A strong correlation with rheumatoid factor or IgA-containing immune complexes was reported ( 325 ). Based on IgG galactosylation, the pSS patients can be classified into two groups: one with comparable galactosylation status as in RA patients with the presence of RF, and the other similar to healthy individuals, and RF seronegative ( 326 ).…”

“…IgG glycosylation can also be controlled at an extracellular level. IgG sialylation has been reported in the bloodstream, through secreted ST6Gal1 ( 326 ). S-glycosyltransferases have also been shown to alter the IgG molecule at sites of inflammation with local platelets serving as nucleotide-sugar donors ( 346 ).…”

Mass Spectrometric Determination of IgG Subclass-Specific Glycosylation Profiles in Siblings Discordant for Myositis Syndromes

“…At the protein level, the effector molecules of the immune system – the antibodies –undergo structural changes in autoimmune rheumatic disorders such as rheumatoid arthritis (RA) 18, 19 , Sjøgrens’s syndrome 20 , psoriatic arthritis, and systemic lupus erythematosus (SLE) 21 . These changes are mainly related to the glycoform distribution of the complex type N -linked glycan attached at Asn 297, the conserved glycosylation site on the antibody constant region.…”