Endocrine Abstracts (2013) 32 P353 | DOI: 10.1530/endoabs.32.P353

Autoantibodies to the insulin- and IGF1-receptor in human sera

Tim Welsink1,2, Christian Schwiebert1,3, Waldemar Minich1 & Lutz Schomburg1

1Institute for Experimental Endocrinology, Charité Universitätsmedizin Berlin, Berlin, Germany; 2ICI immunochemical intelligence GmbH, Berlin, Germany; 3InVivo BioTech Services GmbH, Hennigsdorf, Germany.

Introduction: Autoantibodies (aAB) are characteristic of autoimmune diseases, but may also be found in apparently healthy individuals and precede pathological symptoms. We have recently reported on autoantibodies against the IGF1-receptor (IGF1R-aAB) in control subjects and patients with Graves’ disease (1). The isolated aAB were able to immunoprecipitate the recombinant autoantigen and antagonized IGF1 signaling in vitro. Given the structural similarities between IGF1R and insulin receptor (IR), we decided to establish a diagnostic test for IR-aAB similar to our IGF1R-aAB assay. IR-aAB are of endocrine importance as they are capable of causing insulin resistance type B.

Objective: To compare the prevalence and potential cross-reactivity of IGF1R-aAB and IR-aAB.

Methods: Recombinant variants of both receptors were stably expressed in HEK293 cells and used to establish diagnostic autoantibody assays as described (1). A total of 400 samples were obtained from a commercial supplier and analyzed for IGF1R-aAB and IR-aAB presence. Cross-reactivity of positive sera was tested with recombinant IGF1R and IR.

Results: A comparable number of sera turned out to be positive for IGF1R-aAB and IR-aAB, respectively, with a prevalence of ~5% each. A fraction of positive samples turned out to react with both the IGF1R and the IR indicating either the presence of multiple specific-aAB isoforms or one type of cross-reacting aAB in a given serum. Clonality and cross-reactivity of the aAB identified are currently under investigation.

Conclusion: Our studies demonstrate an unexpected high prevalence of aAB against IGF1R and IR in human sera. In light of case reports on insulin resistance type B, these findings may be of clinical relevance for the present diabetes epidemy, but further studies are needed to test this hypothesis.

1. Minich WB, et al. Journal of Clinical Endocrinology and Metabolism, 2013 (in press, PMID: 23264397).

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