ABSTRACT
Most reports of autoimmune response during infection with the parasite Trypanosoma cruzi have dealt with the cardiomyopathic form of Chagas' disease, but little is known about the mechanisms of tissue damage involved in the gastrointestinal form, which was studied here. Chronically infected patients with a severe gastrointestinal form of Chagas' disease present increased antibody production and proliferative responses to peripheral myelin components, such as myelin basic protein (MBP), which is homologous to the P1 protein fraction of peripheral myelin. T lymphocytes preferentially recognize a region on the MBP molecule (1-30), which suggests that the MBP is a potential target on the peripheral nerve for autoimmune reactions in patients with gastrointestinal lesions resulting from Chagas' disease.
Subject(s)
Chagas Disease/immunology , Enteric Nervous System/immunology , Gastrointestinal Diseases/immunology , Myelin Sheath/immunology , Adult , Animals , Autoantibodies/immunology , Autoantigens/immunology , Autoimmunity/immunology , Brain/immunology , Brain/pathology , Brain/physiopathology , Chagas Disease/physiopathology , Enteric Nervous System/pathology , Enteric Nervous System/physiopathology , Female , Gastrointestinal Diseases/microbiology , Gastrointestinal Diseases/physiopathology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/innervation , Gastrointestinal Tract/physiopathology , Humans , Lymphocyte Activation/immunology , Male , Middle Aged , Myelin Basic Protein/immunology , Myelin Proteins/immunology , Myelin Sheath/pathology , Neurons/immunology , Neurons/pathology , Peripheral Nerves/immunology , Peripheral Nerves/pathology , Peripheral Nerves/physiopathology , Polyradiculoneuropathy/immunology , Polyradiculoneuropathy/microbiology , Polyradiculoneuropathy/physiopathology , T-Lymphocytes/immunology , Trypanosoma cruzi/physiologyABSTRACT
Multiple sclerosis (MS) is a chronic inflammatory disease of the white matter of the central nervous system (CNS) characterized by focal areas of demyelination. Interferon-beta (IFN-beta) provides an effective treatment that lessens the frequency and severity of exacerbations in relapsing-remitting multiple sclerosis (RRMS), but the mechanisms by which IFN-beta is efficient remain uncertain. The data presented here demonstrate that IFN-beta impairs the proliferative response to myelin basic protein (MBP) and myelin, as well as increasing the expression of the CTLA4 intracellular molecule. Moreover, this treatment increases the expression of surface Fas molecules and of the soluble form of these molecules. Our hypothesis is that the increase in Fas and CTLA4 molecules in MS patients may lead to lymphocyte apoptosis, which suggests possible mechanisms underlying the therapeutic response to IFN-beta.
