SLE is the most common of lupus. SLE is an autoimmune disease in which the immune system attacks its tissues, causing widespread inflammation and tissue damage in the affected organs. A complex interaction of impaired apoptotic clearance, upregulation of innate and adaptive immune systems, complement activation, immune complexes, and tissue inflammation culminates in a self-sustained autoimmune process. It can affect the joints, skin, brain, lungs, kidneys, and blood vessels. Cutaneous manifestations occur in about 75% of patients with SLE in the course of the disease. Lupus has no cure, but medical interventions and lifestyle changes can help control it. While many organs and tissues may be heterogeneous SLE, the pattern of clinical manifestations and autoimmune phenomena is heterogeneous among patients and even changes over time in individual patients. For this reason, diagnosis is often difficult or delayed and relies on keen clinical expertise to combine clinical and immunological findings.
Fig.1 LES symptoms.
Glycosylation is one of the most common PTMs that contributes to many biological processes. This enzymatic PTM involves the covalent addition of sugar moieties to the protein. Two known types of Protein Glycosylation are as follows: O-glycosylation, which consists of Glycans linked to oxygen atoms of the amino acid serine (Ser) or threonine (Thr), and N-glycosylation, which is linked to the nitrogen atom of the amino acid asparagine (Asn). Carbohydrate structures also play a key role in the antigenicity of numerous clinically important antigens in adhesion and homing events during inflammatory processes; they comprise robust xenotransplantation antigens and may provide targets for tumor immunotherapy. Additionally, glycosylation is altered in many autoimmune diseases, such as SLE.
As early as 1992, aberrant glycosylation of Ig, such as increased IgG galactosylation, was reported in SLE. Recently, analyses based on ultra-performance liquid chromatography showed that decreased galactosylation, decreased Sialylation, decreased core fucosylation, and increased bisecting N-acetylglucosamine were observed in serum IgG of SLE patients compared with healthy controls. However, another study observed increased serum IgG fucosylation in SLE patients. Low IgG galactosylation was also reported in lupus mice models. Alpha-mannosidase II is an enzyme that modulates the trimming of mannose residues from hybrid N-linked Oligosaccharides. A α-mannosidase II-deficient mice presented a systemic autoimmune disease similar to human SLE, suggesting a potential pathogenic role of mannose in SLE. Decreased galactosylation, decreased sialylation, and increased bisecting glycan were positively associated with serum antinuclear antibody (ANA) and SLE organ involvement. Another study demonstrated that increased serum IgG fucosylation was associated with high SLE disease activity and low serum C3 levels. These associations make IgG glycosylation patterns a promising biomarker for SLE disease activity.
The goals of treatment in lupus are 1) maintain the lowest degree of activity using immunomodulators, immunosuppression as appropriate and avoiding known triggers, 2) prevent organ damage from active lupus, 3) reduce comorbidities secondary to lupus and its treatment, especially accelerated atherosclerosis, the major cause of death, and 4) address fatigue and pain, which often are not associated with active lupus. This translates into avoidance of known triggers of flares, the need for sun protection, maximization of immunomodulators (hydroxychloroquine and vitamin D, including monitoring for adherence), and control of active disease with immunosuppression or biologics when required.
CD BioGlyco is a biotechnology company with large experience in developing glycobiology-related products and services. To promote the development of immunomodulators in SLE, we have developed a powerful Carbohydrate-based Glycomedicine Development Platform to provide customers with comprehensive, high-quality, and affordable services. If you are interested in our services, please feel free to contact us for more detailed information.