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Abstract
The therapeutic use of exogenous insulin of animal origin for the treatment of diabetes mellitus has been associated with the development of insulin antibodies, which raises concerns regarding the safety and efficacy of this formulation. With the advent of recombinant DNA technology and the generation of insulin with human-like sequences, the production of insulin antibodies has been reduced but not eliminated. As part of the analysis of immunogenicity induced by therapeutic proteins and to evaluate the immunogenic profile of three commercial formulations of human exogenous insulin (regular, neutral protamine Hagedorn (NPH), and glargine) we evaluated the presence of insulin antibodies in 29 serum samples from volunteers with type 2 diabetes, and we characterized their cross-reactivity, IgG subclass profile, and ability to form immune complexes. To this end, volunteers were classified into three groups according to their current insulin therapy: a) Regular and NPH insulin (n=10); b) NPH (n=9), and c) glargine (n=10). For the detection, characterization, and evaluation of the IgG subclasses we used an indirect ELISA test, and for the detection of immune complexes formed by insulin antibodies and exogenous insulin, capture ELISA. Our results evidenced that: i) Each insulin formulation was recognized differentially by the insulin antibodies suggesting a greater immunogenic potential for NPH insulin and a lower one for glargine insulin; ii) the IgG subclasses profile of insulin antibodies in humans was different for each formulation; the IgG3 subclass for NPH insulin was predominant in volunteers treated with regular and NPH insulin; iii) the presence of insulin antibodies was not associated with alterations in the metabolic parameters analyzed, and iv) immune complexes composed of exogenous insulin antibodies were not detected in the sera of diabetic volunteers. The results obtained in this study allowed us to conclude that there are differences between the immunogenic profile of the insulin formulations tested, which has significant value in the analysis of their immunogenicity with regard to their safety and efficacy. © 2018. Acad. Colomb. Cienc. Ex. Fis. Nat.References
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