Christiane Hampe, Ph.D.
Metabolism, Endocrinology and Nutrition
Research Associate Professor of Medicine
My research interests are the dissection of the role of autoantibodies to the 65kDa isoform of glutamate decarboxylase (GAD65) (GAD65Ab) in the pathogenesis of type 1 diabetes. GAD65Ab are found in 70-80% of newly diagnosed type 1 diabetes patients. While these autoantibodies are widely accepted as markers for the disease, preliminary data indicate that disease-specific GAD65Ab modulate T-cell responses. It is of great importance to understand the effect of GAD65Ab on processing and presentation of GAD65. The central hypothesis is that autoantibody modulation of T cell mediated autoimmunity plays a key role in the pathogenesis of type 1 diabetes.
It is well established that antibodies can modulate T cell responses either by enhanced antigen uptake (receptor-mediated endocytosis) or alteration of antigen processing, or both. Antibodies can both suppress and boost the presentation of certain peptides, hence the analysis of heterogeneous GAD65Abs, as present in patients’ sera, will be difficult. The rationale of the project is: 1) to generate monoclonal antibodies to defined regions of GAD65, and 2) to use those unique reagents to test how they deviate the T cell response already shown to be enhanced by GAD65Ab-positive sera. The antibodies will be humanized to allow their usage in human B cell transfection and APC presentation to human T cells.
Padoa CJ, Banga JP, Madec AM, Ziegler M, Schlosser M, Ortqvist E, Kockum I, Palmer J, Rolandsson O, Binder KA, Foote J, Luo D, Hampe CS: Recombinant Fabs of human monoclonal antibodies specific to the middle epitope of GAD65 inhibit type 1 diabetes-specific GAD65Abs. Diabetes 52:2689-2695, 2003.
Maldonado M, Hampe CS, Gaur LK, D’Amico S, Iyer D, Hammerle LP, Bolgiano D, Rodriguez L, Rajan A, Lernmark A, Balasubramanyam A: Ketosis-prone diabetes: dissection of a heterogeneous syndrome using an immunogenetic and beta-cell functional classification, prospective analysis, and clinical outcomes. J Clin Endocrinol Metab 88:5090-5098, 2003.
Luo D, Rogers CN, Hampe CS, Lernmark A: Molecular engineering of biotin-glutamic acid decarboxylase 65 fusion protein (Biotin-GAD65) for non-radioactive GAD65 antibody assay. J Biotechnol 103:249-255, 2003.
Elfving AM, Lindberg BA, Landin-Olsson M, Hampe CS, Lernmark A, Ivarsson SA: Islet cell autoantibodies in cord blood from children with blood group incompatibility or hyperbilirubinemia. Autoimmunity 36:111-115, 2003.
Niklasson B, Heller KE, Schonecker B, Bildsoe M, Daniels T, Hampe CS, Widlund P, Simonson WT, Schaefer JB, Rutledge E, Bekris L, Lindberg AM, Johansson S, Ortqvist E, Persson B, Lernmark A: Development of type 1 diabetes in wild bank voles associated with islet autoantibodies and the novel ljungan virus. Int J Exp Diabesity Res 4:35-44, 2003.
Chessler SD, Hampe CS, Ortqvist E, Simonson WT, Bekris L: Immune reactivity to GAD25 in type 1 diabetes mellitus. Autoimmunity 35:335-341, 2003.
Binder KA, Banga JP, Madec AM, Ortqvist E, Luo D, Hampe CS: Epitope analysis of GAD65Ab using fusion proteins and rFab. J Immunol Methods 295:101-109, 2004.
Gilliam LK, Binder KA, Banga JP, Madec AM, Ortqvist E, Kockum I, Luo D, Hampe CS: Multiplicity of the antibody response to GAD65 in Type I diabetes. Clin Exp Immunol 138:337-341, 2004
Maioli M, Alejandro E, Tonolo G, Gilliam LK, Bekris L, Hampe CS, Obinu DA, Manconi A, Puddu L, Lynch K, Lernmark A; Study Group for the Genetics of Diabetes in Sardinia: Epitope-restricted 65-kilodalton glutamic acid decarboxylase autoantibodies among new-onset Sardinian type 2 diabetes patients define phenotypes of autoimmune diabetes. J Clin Endocrinol Metab 89:5675-5682, 2004.
Luo D, Gilliam LK, Greenbaum C, Bekris L, Hampe CS, Daniels T, Richter W, Marcovina SM, Rolandsson O, Landin-Olsson M, Kockum I, Lernmark A: Conformation-dependent GAD65 autoantibodies in diabetes. Diabetologia 47:1581-1591, 2004.
Luo D, Rogers CN, Steed JT, Gilliam LK, Hampe CS, Lernmark A: Development of glutamic acid decarboxylase 65 (GAD65) autoantibody assay using biotin-GAD65 fusion protein. J Biotechnol 111:97-104, 2004.
Hampe CS, Wallen AR, Schlosser M, Ziegler M, Sweet IR: Quantitative evaluation of a monoclonal antibody and its fragment as potential markers for pancreatic beta cell mass. Exp Clin Endocrinol Diabetes 113:381-387, 2005.
Padoa CJ, Crowther NJ, Thomas JW, Hall TR, Bekris LM, Torn C, Landin-Olsson M, Ortqvist E, Palmer JP, Lernmark A, Hampe CS: Epitope analysis of insulin autoantibodies using recombinant Fab. Clin Exp Immunol 140:564-571, 2005.
Schlosser M, Banga JP, Madec AM, Binder KA, Strebelow M, Rjasanowski I, Wassmuth R, Gilliam LK, Luo D, Hampe CS: Dynamic changes of GAD65 autoantibody epitope specificities in individuals at risk of developing type 1 diabetes. Diabetologia 48:922-930, 2005.