ABSTRACT
We previously demonstrated the induction of IFN-gamma in polyneuropathy patients associated with monoclonal gammopathy, but not in patients with presumably non-immunological types of neuropathy. We herein examined mechanism involving release of neutralizing autoantibodies (Aabs) to IFN-gamma in sera from those patients. In contrast to polyneuropathy patients with monoclonal gammopathy, patients with polyneuropathy of presumably non-immunological types showed increased production of neutralizing Aabs specific for IFN-gamma. These results demonstrate a role for autoimmunity in cytokine regulation. However, their association to the clinical manifestations of the disease requires further investigations, which are necessary for future consideration in therapeutic strategies.
Subject(s)
Autoantibodies/blood , Interferon-gamma/immunology , Monoclonal Gammopathy of Undetermined Significance/immunology , Peripheral Nervous System Diseases/immunology , Adult , Aged , Aged, 80 and over , Antibody Specificity , Female , Humans , Male , Middle Aged , Monoclonal Gammopathy of Undetermined Significance/complications , Neutralization Tests , Peripheral Nervous System Diseases/complicationsABSTRACT
Guillain-Barré syndrome (GBS) is an immune-mediated demyelinating disease of peripheral nerves that is often preceded by an infection and is usually self-restricted. The Th1 cytokine interferon-gamma (IFN-gamma) is thought to be disease-promoting in organ-specific autoimmune diseases. We report the spontaneous induction of IFN-gamma and a mechanism involving the generation of neutralizing autoantibodies (Aabs) to IFN-gamma that may regulate the disease. Numbers of cells spontaneously secreting IFN-gamma in peripheral blood were augmented in GBS, in particular at the peak of clinical disease, and decreased during recovery. This decrease was associated with elevated serum concentrations of IgG Aabs to IFN-gamma. These Aabs specifically bound to IFN-gamma and neutralized its effects in a biological assay. Aabs to IFN-gamma are proposed to be another important regulatory mechanism in IFN-gamma-driven GBS.
Subject(s)
Autoantibodies/immunology , Interferon-gamma/immunology , Polyradiculoneuropathy/immunology , Adult , Aged , Antibody Specificity , Autoantibodies/blood , Autoantibodies/metabolism , Histocompatibility Antigens Class II/biosynthesis , Histocompatibility Antigens Class II/blood , Humans , Interferon-gamma/biosynthesis , Interferon-gamma/blood , Middle Aged , Neutralization Tests , Polyradiculoneuropathy/blood , Polyradiculoneuropathy/metabolismABSTRACT
BACKGROUND: We have recently described the induction of anti-cytokine autoantibodies during bacterial infections and autoimmune diseases as a mechanism for cytokine regulation. METHODS: Herein, we study the occurrence of autoantibodies to pro- and anti-inflammatory cytokines in cerebrospinal fluid and plasma from patients with multiple sclerosis, aseptic meningitis and stroke. RESULTS: Increased levels of autoantibodies to interferon gamma, tumour necrosis factor alpha, interleukin 4 and interleukin 10 were detected in both compartments of multiple sclerosis and aseptic meningitis patients. Interestingly, in cerebrospinal fluid from stroke patients, only autoantibodies to interleukin 4 and interleukin 10, but not interferon alpha or tumour necrosis factor alpha were detected. No significant autoantibody levels were registered in plasma from stroke patients against all four cytokines compared with healthy control subjects. The latter revealed very low autoantibody levels in plasma and no detectable autoantibodies in cerebrospinal fluid. CONCLUSIONS: Our data show for the first time the occurrence of cytokine autoantibodies in these diseases, but their biological significance is unclear.
