[One step towards restoration of self-tolerance in human autoimmune diseases].
In developed countries the incidence of autoimmune insulin-dependent or type 1 diabetes as the one of all autoimmune diseases has steadily increased over the last decades. Conventional therapy of type 1 diabetes is essentially palliative namely, chronic delivery of exogenous insulin that is associated with major constraints (multiple daily parenteral administration, serious risks linked to hypoglycemic episodes) and incomplete effectiveness in preventing severe degenerative complications. This explains the growing attention on modern therapeutic strategies using biological agents such as CD3 monoclonal antibodies that allow 'reprogramming' the immune system to restore self-tolerance to pancreatic beta cell antigens. This strategy which proved successful in the experimental setting has recently been translated to the clinic with very encouraging results. CD3 antibodies may represent a new category of drugs affording a real cure for autoimmunity namely, inhibiting the pathogenic immune response while preserving the host reactivity to unrelated antigens.
Chatenoud
Lucienne
L
Inserm U580, Faculté René-Descartes Paris 5, Hôpital Necker- Enfants-Malades, 161, rue de Sèvres 75015, Paris, France. chatenoud@necker.fr
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D015551:Autoimmunity / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017637:Clonal Deletion; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D005968:Glutamate Decarboxylase / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D007231:Infant, Newborn; D007328:Insulin / Q000276:immunology / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016853:Muromonab-CD3 / Q000276:immunology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D017634:Self Tolerance / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013934:Thymectomy / Q000009:adverse effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies; D001324:Autoantigens; D017252:CD3 Complex; D018834:Chaperonin 60; D007074:Immunoglobulin G; D007328:Insulin; D016853:Muromonab-CD3; D005968:Glutamate Decarboxylase; C502540:teplizumab