Reactivity of agalactosyl IgG with rheumatoid factor

Immunoglobulin G galactosylation and sialylation are associated with pregnancy-induced improvement of rheumatoid arthritis and the postpartum flare: results from a large prospective cohort study

“…Since RF preferentially binds to agalactosyl IgG, this would result in more pronounced RF-agalactosyl IgG interaction and hence more inflammation [16,17]. Secondly, the pathogenicity of agalactosyl IgG is thought to be associated with its ability to activate the complement pathway via binding to mannose-binding lectin (MBL) [18].…”

Adenoviral delivery of IL-1 receptor antagonist abrogates disease activity during the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice

“…This mouse model shows marked synovial and periarticular inflammation with articular erosion caused by granulation tissues invasion [26]. In addition, this mouse model shows elevated levels of antibodies, such as, inflammatory T helper type (Th) 1 driven IgG2a and Th2 driven IgG1 antibodies to collagen type II (CII), thus suggesting that the mechanism involved is consistent with the development of autoimmunity in human [27][28][29]. In this regard, IL-1Ra −/− mice closely resemble RA patients, and thus those mice promises to be more useful than other animal arthritis models.…”

The pivotal nature of sugars in normal physiology and disease

“…Interestingly, the G0-dependent binding, characteristic of these RFs, was associated with their mono-reactivity and, in particular, their functional affinity [149], suggesting the possibility that certain high affinity RFs may in the presence of high levels of agal-IgG be rendered pathogenic. Other studies have shown that the RF reactivity is higher with agalactosylated IgG than with heated-intact or intact IgG [143], and that it can also be affected by the levels of Fuc and bisGlcNAc [153]. -IgG-RFs; Critical to RA pathology is the fact that IgG-G0 can also affect IgG RF affinity and binding; Auto-Ab activity of IgG RF increases with decreasing levels of Gal [152], and RA synovial IgG-RF preferentially binds to chemically agalactosylated-Fc and Fab-2 moieties [141].…”

“…This is an important paradigm, which may explain the increased levels of ICs and their atypical glycosylation status in RA [138,149]. It may also shed more light on how these ICs may induce/perpetuate the pathological processes in RA [40,86,130,143,152,153]; in particular in the synovial joint, which is the site for both increased production of hypogalactosylated IgG and RFs [141,154].…”