Immunological studies on glycated human IgG

Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity

“…As has been shown here, detailed analysis of IgG glycoforms arising through a standard assay using a 2,6 sialic acid transferase established that a variety of AGEs, including 5-methylimidazol-4-one and aggregates, can be easily introduced if using unqualified processes. All of these side products would impede the use of this preparation in the clinic, because AGEs have the potential to be immunogenic (32,33,(39)(40)(41), and the formation of aggregates may result in the development of immune-related safety concerns, such as cytokine-release syndrome (7,42). In addition, these side products could diminish the sialic acid-dependent immunomodulatory activity.…”

A clinical correlation of anti-DNA-AGE autoantibodies in type 2 diabetes mellitus with disease duration

“…The aim of disease prediction is its prevention. Autoantibodies of various AGEs and amadori products have also been reported in the sera of diabetic patients and other diseases [4,13,34,[45][46][47]. In vitro experiments have demonstrated that immunoglobulins purified from diabetic sera are capable of binding to platelets [43] and endothelial cells [42] and involved in the pathogenesis of vascular diabetic complications.…”

Glycation of antibodies: Modification, methods and potential effects on biological functions

“…37,38 In comparison, a therapeutic mAb in circulation is typically at 0.2/mg/ml, with an overall glycation level at 10-25%. 5,8,33,37,[39][40][41][42] The average lysine residue glycation rate is similar among the therapeutic antibodies, endogenous human IgG and human serum albumin. 37 If the IgG does not contain a highly reactive glycation site, then the glycation will be spread across the whole molecule with low level glycation on all susceptible glycation sites under endogenous conditions.…”

“…This method has been used to measure poly-lysine 62 and glycated albumin. 63 NBT analysis was applied to glycated antibody by Ahmad, et al 39 in 2012. 37 Recently, Butko, et al 21 reported that several AGEs found in manufactured recombinant mAb were strongly related to a color change in the antibody solution, and that AGEs are partially responsible for the color of mAb products.…”

“…The AGEs are more immunogenic than normal antibody in animal models. 39 The presence of AGEs was found in rheumatoid arthritis (RA) patients as the result of inflammation. AGE-damaged antibody could trigger an immune response by generating anti-IgG autoantibodies in RA patients.…”