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Somatically mutated high-affinity autoantibodies are a hallmark of some autoimmune diseases, including systemic lupus erythematosus. It has long been presumed that germinal centers (GCs) are critical in autoantibody production, because they are the only sites currently believed to sustain a high rate of somatic hypermutation. Contrary to this idea, we found that splenic autoreactive B cells in autoimmune MRL.[Fas.sup.lpr] mice proliferated and underwent active somatic hypermutation at the T zone--red pulp border rather than in GCs. Our results implicate this region as an important site for hypermutation and the loss of S cell self-tolerance., The activation of autoreactive B cells is pivotal for the development of systemic autoimmune diseases, because these lymphocytes secrete pathogenic autoantibodies and promote the activation of pathogenic autoreactive T cells [...]

Rasmussen's encephalitis is a progressive childhood disease of unknown cause characterized by severe epilepsy, hemiplegia, dementia, and inflammation of the brain. During efforts to raise antibodies to recombinant glutamate receptors (GluRs), behaviors typical of seizures and histopathologic features mimicking Rasmussen's encephalitis were found in two rabbits immunized with GluR3 protein. A correlation was found between the presence of Rasmussen's encephalitis and serum antibodies to GluR3 detected by protein immunoblot analysis and by immunoreactivity to transfected cells expressing GluR3. Repeated plasma exchanges in one seriously ill child transiently reduced serum titers of GluR3 antibodies, decreased seizure frequency, and improved neurologic function. Thus, GluR3 is an autoantigen in Rasmussen's encephalitis, and an autoimmune process may underlie this disease., Rasmussen's encephalitis is a rare, progressive, catastrophic disease of unknown pathogenesis that begins in the first decade of life, affecting previously normal children[1]. The disease affects the cortex of a [...]

A DNA-nicking activity was detected in the sera of patients with various autoimmune pathologies and was shown to be a property of autoantibodies. The DNA hydrolyzing activity, which was purified by affinity and high-performance liquid chromatography, corresponded in size to immunoglobulin M (IgM) and IgG and had a positive response to antibodies to human IgG. The DNA hydrolyzing autoantibodies were stable to acid shock and yielded a DNA degradation pattern that was different from that of deoxyribonuclease (DNase) I and blood DNase., Patients with autoimmune diseases produce autoantibodies to nucleoprotein complexes (1), to DNA, and to enzymes that participate in nucleic acid metabolism (2). In autoimmune diseases, there can be spontaneous induction [...]

Autoreactive Epitope Defined as the Anticodon Region of Alanine Transfer RNA NATIVE NUCLEIC ACIDS DO NOT stimulate significant antibody production when injected into experimental animals, but such antibodies can be [...]

Catalytic Hydrolysis of Vasoactive Intestinal Peptide by Human Autoantibody ANTIBODIES, LIKE ENZYMES, ARE CAPABLE OF CATALYSIS. The diversity and specificity of the immune response hold the promise that antibodies can [...]

Inhibition of Self-Binding Antibodies (Autobodies) by a V.sub.H.-Derived Peptide ANTIBODIES, MEMBERS OF THE IMMUNOGLOBULIN (Ig) supergene family, are evolutionary related and functionally connected to form the basis of the immune [...]