The Immunoglobulin Class, the Subclass and the Ratio of k:λ Light Chain of Autoantibodies to human Insulin in Insulin Autoimmune Syndrome

Abstract

The immunoglobulin class, subclass and the k:lambda light chain ratio of insulin autoantibodies were determined in the sera of twenty-four patients with insulin autoimmune syndrome. All sera proved to be of the IgG immunoglobulin class but exhibited various IgG1:IgG2:IgG3:IgG4 ratios. The ratio of k:lambda light chain ranged from 1:0.13 to 1:0.75 with the exceptions of two sera that were characterized as IgG1(k) and IgG1(lambda).

Resolution of dysglycaemia after treatment of monoclonal gammopathy of endocrine significance

“… 27-31 They are most commonly of the IgG class without predominance of a particular subclass or light chain. 32 Further examination in this case confirmed the insulin-binding antibody to be IgG2 kappa, consistent with the paraprotein and increased serum concentration of IgG2. In the context of severe dysglycaemia requiring clinical intervention, discriminating the 2 entities had important management implications: although aberrant insulin kinetics are induced by a similar mechanism in both polyclonal IAS and monoclonal insulin binding, autoantibody production in IAS may be self-limiting, while in PCD, targeted PCDT is needed for antibody depletion.…”

Differential Immunogenetic Determinants of Polyclonal Insulin Autoimmune Syndrome (Hirata's Disease) and Monoclonal Insulin Autoimmune Syndrome

“…binding to human insulin (13) and the diversity of the ratio of K-to-\ light chain (26). HLA serological typing and DNA typing.…”

Identification of Monoclonal Insulin Autoantibodies in Insulin Autoimmune Syndrome Associated with HLA-DRB1*0401

“…In the immunoprecipitation analysis using antibodies against human immunoglobulin heavy chains and light chains, only antibodies against human IgG and ĸ showed significantly increased precipitation of [ 125 I] human insulin compared to control, which indicated that immunoglobulin class of insulin autoantibodies was exclusively IgG-ĸ in the patient (table 1) [10]. These results strongly suggested that the patient had monoclonal insulin autoantibodies.…”

“…Immunoprecipitation analysis demonstrated that immunoglobulin class of insulin autoantibodies was exclusively IgG-ĸ. It has been described that a single binding affinity of insulin autoantibodies and ĸ or λ chain predominance in insulin autoantibodies are important features of monoclonal insulin autoantibodies [9, 10]. The present results, therefore, indicate that the patient has monoclonal insulin autoantibodies, which is extremely rare in Japan [4, 9].…”