This sugar structure maintains the conformational arrangements of the Fc domains, as well as the hinge regions that participate in the activation of the classical complement pathway and monocyte binding. common in certain ethnic groups. As an Vitamin A example, systemic lupus erythematosus (SLE) affects nearly three times as many African-American or Hispanic individuals than Caucasians. Genetics has been identified as a risk factor in certain autoimmune diseases, such as multiple sclerosis and SLE. In fact, it has been discovered that those diseases have been diagnosed in several members of the same families and precisely diagnosed in homologous twins [2]. Environmental factorsincluding infectious agents, pollution and human behavior, for example, the use of drugsfavor those diseases, as well [3]. On this matter, procainamide and hydralazine drugs can be used to modify deoxyribonucleic acid (DNA) methylation, leading to the expansion Rabbit Polyclonal to Shc (phospho-Tyr427) of autoreactive cluster of differentiation (CD)4+ T cells [4]. Regarding the infectious agent impact, several mechanisms have been described, suggesting a molecular mimicry between the infection agent and self-molecules, leading to the development of autoreactive T cells [5]. Furthermore, epidemiological studies have suggested that smoking is an independent risk factor for several autoimmune diseases such as SLE, rheumatoid arthritis (RA) and systemic sclerosis [6]. Finally, age is suspected to be important, for example, in female patients with RA due to a decrease in Vitamin A estrogen production. This hormone influences the induction of the -galactoside 2,6-sialyltransferases 1 (ST6Gal I) in plasmablasts. In these cells, the role of this enzyme is to add sialic acid (Sia) residues, notably on the Fc (Fragment, crystallizable) of type G immunoglobulins (IgG). Consequently, in a menopausal condition, the rate of IgG (and particularly IgG autoantibodies with a low Sia content on their Fc) increases and contributes to the development of a proinflammatory environment [7]. The Fc region Vitamin A is responsible for the implementation of physiological effects, including cell lysis, the degranulation of mast cells, basophils, eosinophils and opsonization [8]. The regulation of these effects is induced by variations of Fc glycosylation, such as sialylation and galactosylation as well with, for example, affinity changing of antibodies to Fc receptors on immune cells, or ligation of the first component of classical complement activation [9,10,11]. Recently, glycosylation was highlighted as a factor involved in the development of autoimmune diseases [12]. Glycosylation involves several enzymatic reactions occurring mainly in the endoplasmic reticulum and in the Golgi apparatus, leading to the formation of sophisticated glycans on lipids and proteins. This phenomenon affects cell interactions and the activities of the secreted proteins [13,14,15,16,17]. For example, the glycosylation of T helper (Th) cells modulates their sensitivity to a glycan-binding anti-inflammatory protein: galectin 1. The lack of sialylation on Th1 and Th17 cells makes them vulnerable to galectin-1 mediated cell death, whereas Th2 remains unaffected. Mice Vitamin A that are deficient in galectin-1 develop autoimmune inflammation [18]. A confirmation of this effect has been observed in autoimmune encephalomyelitis models. Galectin-1 binds to ganglioside M1 (GM1) in effector T cells and consequently, inhibits autoimmune manifestations [19]. Another galectin, galectin-9, attenuates Th1 responses and provides protection against the onset of autoimmune diabetes in vivo [20]. Moreover, sialylation modulates cellular functions by other lectins, such as sialic acid-binding immunoglobulin-like lectins (Siglecs), which are immune-modulatory receptors within the mammalian immune system. Among them, CD22 (Siglec-2) appears to be an important negative regulator of B-cell activity [21]. Finally, sialyl motifs, such as sialyl-Lewis X, modulate leukocyte trafficking to secondary lymphoid organs and inflammatory sites through selectins [22]. These observations highlight the important role of sialylation in autoimmune diseases and suggest that targeting sialylation would result in an interesting treatment strategy [23]. The aim of this review is to summarize the impact of sialylation on autoimmune diseases and propose novel therapeutic approaches based on its regulation. 2. The Hyposialylation of Autoantibodies and the Generation of Anti-Sialic Acid Antibodies Contribute to the Development of Autoimmune Diseases Vitamin A 2.1. The Hyposialylation of Autoantibodies Is Positively Correlated with the Severity of the Disease Chronic inflammatory demyelinating polyneuropathy (CIDP) is associated with acute inflammatory demyelinating polyradiculoneuropathy and is the most common form of Guillain-Barr syndrome, an inflammatory autoimmune disease of the peripheral nervous system. The level of IgG-Fc sialylation is inversely correlated with CIDP clinical severity [24]. In granulomatosis.