Immunomodulation with human recombinant autoantigens.
The loss of beta cells in type 1 diabetes is the consequence of a T cell-dependent autoimmune attack. Autoantibodies against GAD65 (Mr 65.000 isoform of glutamic acid decarboxylase), IA-2 (insulinoma-associated protein IA-2) or insulin, alone or in combination, predict disease. Preclinical studies in spontaneously diabetic rodents suggest that immunomodulation with autoantigens might alter the course of autoimmune diabetes. Oral insulin reduces the development of diabetes in risk subjects with high insulin autoantibody levels. Giving alum-formulated GAD65 to patients classified with latent autoimmune diabetes of the adult (LADA) is safe and suggests possible immunomodulating effects of GAD65. Future immunomodulation trials might better ascertain subjects based on HLA genetic risk factors, the level of insulin that is still produced or by combining autoantigens with, for example, anti-CD3 antibodies, to induce antigen-specific tolerance and thereby a long-lasting protection for beta cells.
Lernmark
Ake
A
The University of Washington, Department of Medicine, Seattle, WA 981905, USA. ake@u.washington.edu
Agardh
Carl-David
CD
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology*; D007167:Immunotherapy; D007328:Insulin / Q000276:immunology / Q000627:therapeutic use; D007527:Isoenzymes / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D011994:Recombinant Proteins / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D007155:Immunologic Factors; D007328:Insulin; D007527:Isoenzymes; D008565:Membrane Proteins; D011994:Recombinant Proteins; C516862:PTPRN protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2