Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004364 (autoimmune disease)
 24,845 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new model of an autoimmune disease of the neuromuscular junction was obtained by injection of acetylcholine receptor purified from rat denervated muscles into Balb/c mice. Anti-rat, then anti-mouse acetylcholine receptor antibodies, appear in mouse serum during the immunization procedure. Electrophysiological investigations performed on immunized mice reveal a neuromuscular block similar to that found in myasthenia gravis. Not a single mouse with objective signs of muscular weakness was lacking anti-mouse acetylcholine receptor antibodies but no correlation was found between their level and the severity of the disease.
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PMID:Experimental myasthenia in Balb/c mice immunized with rat acetylcholine receptor from rat denervated muscle. 106

An increased frequency of antibodies to native DNA, thymocytes, and striated muscle was found in patients with myasthenia gravis (MG). The prevalence of such antibodies lends considerable support to the concept of MG as an autoimmune disorder and militates in favor of major abnormalities in the thymic dependent immune system. There was no correlation between serum-blocking activity to acetylcholine receptor protein and antibodies to thymocytes.
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PMID:Antibodies to nucleic acids in myasthenia gravis. 108 33

Synthetic peptides corresponding to selected sequences from the nicotinic acetylcholine receptor (AChR) were employed to identify possible antigenic determinants within the receptor which can modulate the anti-AChR response and experimental autoimmune myasthenia gravis (EAMG). Immunization of rabbits with peptides T alpha 73-89, T alpha 351-368, T delta 354-367 and H alpha 351-368, prior to AChR inoculation, affected the course of EAMG in six out of eight rabbits. These six protected rabbits survived three inoculations of AChR and survived for at least five months after the third injection with AChR, whereas control rabbits died following one or two injections of AChR. The survival of peptide-preimmunized rabbits injected with AChR seemed to correlate with the antibody specificities in immunoblots. Following AChR inoculation there was a shift in reactivity, from a subunit-restricted response, to reactivity with all subunits of the receptor. This shift was delayed in protected rabbits. This may indicate that the reactivity with the entire Torpedo receptor molecule represents a loss of tolerance to AChR which culminates in the autoimmune disease, EAMG.
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PMID:Modulation of anti-acetylcholine receptor antibody specificities and of experimental autoimmune myasthenia gravis by synthetic peptides. 128 97

CD5+ B cells comprise a subset of B lymphocytes that may play a pathogenetic role in the development of human autoimmune disease. We previously reported a high-frequency phenotype (greater than 30% CD5+ B cells) in the peripheral blood of 57% of myasthenia gravis (MG) patients and 13% of controls. We have now examined additional patients (n = 41) and controls (n = 27) and continue to find that 44% of MG patients have a high-frequency phenotype of CD5+ B cells compared with 7% of controls. Serial studies showed that the frequency of CD5+ B cells in peripheral blood remained fairly stable for controls and that it may decrease with immunosuppressive therapy of MG patients. In patients receiving anticholinesterase only or no therapy (n = 21), the age at onset of MG, presence or absence of detectable serum anti-acetylcholine receptor antibody, clinical extent of MG, and the duration of disease may affect the frequency of CD5+ B cells in the blood.
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PMID:Effect of clinical status and treatment on the frequency of CD5+ B cells in patients with myasthenia gravis. 137 46

The acetylcholine receptor (AChR) of muscle is the target of the pathogenic antibodies in the human autoimmune disease myasthenia gravis (MG). For studies on the autoreactive T cells presumed to be responsible, use of intact human autoantigen would be optimal, but it was thought to be prohibitively scarce. However, adsorption to the surface of immunomagnetic particles (Dynabeads) of intact AChR from whole muscle extracts or from affinity-purified preparations, using mouse anti-human AChR Mabs, largely overcomes this problem. Together with antigen presenting cells (APC), this bead-bound AChR has consistently and maximally stimulated an established MG T cell line (previously selected with recombinant human AChR alpha subunit) that recognises the 144-156 region of the human alpha sequence (Ong et al., 1991). For equivalent T cell stimulation, bead-bound AChR was at least 10(3) times more potent than soluble AChR or recombinant alpha subunit, and 10(6) times more potent than peptide 144-156, implying that antigen in this form is targetted very efficiently to APC and thus to T cells. Finally, we have obtained similar results with T cells specific for other antigens suggesting that this method may have wider applications.
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PMID:Stimulation of human T cells by sparse antigens captured on immunomagnetic particles. 138 45

The nicotinic acetylcholine receptor (AChR), a pentameric complex of alpha 2 beta gamma delta subunits, is the autoantigen in the human autoimmune disease myasthenia gravis (MG). Anti-AChR antibodies are found in approximately 90% of MG patients and using indirect methods (competitive binding to solubilized AChR), peptides, or synthetic peptides, the majority of these antibodies have been shown to bind to the AChR alpha subunit. In order to determine directly the AChR subunit specificities of MG antibodies, we employed as antigens a novel set of hybrid AChR composed of species cross-reacting and non-cross-reacting subunits stably expressed in fibroblasts. Sequence similarities of homologous subunits among species can vary widely, with mammalian subunits having 87%-96% identity and Torpedo-mammalian subunits having 54%-80% identity. These findings are reflected in antigenic specificities, with human anti-AChR antisera frequently recognizing mouse AChR but rarely recognizing Torpedo. By establishing separate cell lines stably expressing all-Torpedo, all-mouse, and different combinations of Torpedo and mouse subunits, we were able to provide the first direct evidence of a predominant anti-alpha subunit specificity in MG antisera. Functional hybrid AChR stably expressed in an intact cell membrane provide us with a system that best mimics the in vivo environment of the MG antibody in a binding assay. Such a system allows us to investigate a perplexing observation in the field: a poor correlation between the patient's clinical status and antibody titer. Those antibodies which can interfere with AChR function, such as ones with the ability to cross-link AChR and induce their accelerated internalization and degradation (antigenic modulation) might represent a subpopulation of MG antibodies important in disease induction or maintenance. In this report, we demonstrate that wild-type and hybrid AChR expressed in fibroblasts can be antigenically modulated by intermolecular cross-linking antibodies as AChR are in native muscle cells. Because we can monitor dynamic interactions between AChR and MG antibodies, this system may allow us to define crucial pathogenic epitopes in MG by expressing hybrid, chimeric, and mutant AChR.
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PMID:Use of Torpedo-mouse hybrid acetylcholine receptors reveals immunodominance of the alpha subunit in myasthenia gravis antisera. 138 57

Myasthenia gravis is considered to be an autoimmune disease in which several factors reciprocally influence the clinical type and course. We investigated the relative importance of the following factors: anti-acetylcholine receptor antibody (AChR Ab), HLA, age at onset, autoimmunity, thymic abnormality, duration of treatment, change in AChR Ab titer and immunosuppressive therapy. The pretreatment-AChR Ab titer and HLA were shown to significantly influence the clinical type. On the other hand, the age at onset significantly influenced the clinical course. The finding that with an onset at less than 5-year-old there was a tendency for a good prognosis suggests an association between the immaturity of the muscle and immune systems, and the clinical course.
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PMID:Factors influencing the clinical type and course of myasthenia gravis. 162 31

Previous studies have demonstrated that immunization of BALB/c mice with alpha(1----3) dextran (Dex) is accompanied by a reduction in the subsequent immune response to the acetylcholine receptor (AChR), depending on the timing of the Dex administration relative to AChR challenge. Here, we report that suppression of the anti-AChR response can be transferred by a monoclonal antibody, known as DX2, which is specific for Dex. Serum transfer experiments have also supported the notion that antibody is important for this effect. In addition, two new idiotypic markers have been defined that are expressed mainly by antibodies against Dex, including DX2. The anti-idiotypic reagents (Sh135 and EB5) are derived from the immune response to the AChR. A human monoclonal antibody which binds to Dex (SR 11) resembles the BALB/c antibodies that are involved in the suppression of the anti-AChR response. These findings emphasize the functional relevance of the AChR-Dex network not only for the BALB/c immune response to the AChR, but also for humans with the autoimmune disease, myasthenia gravis.
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PMID:Monoclonal antibody against alpha(1----3) dextran transfers suppression of the immune response to the acetylcholine receptor. 169 30

Helper T lymphocytes recognize fragments of foreign (or self) antigens in the peptide-binding clefts of major histocompatibility complex class II molecules; their activation is a crucial step in the induction of many immune and autoimmune responses. While studying the latter, we raised a T-cell line from the thymus of a myasthenia gravis patient against recombinant alpha subunit of the human acetylcholine receptor, the target of this autoimmune disease. The line responds to the 144-156 region of the human sequence and not to the same region of the electric fish homolog, which differs by only three residues. These CD4+ T cells recognize this epitope only in the context of HLA-DR4 class II molecules, of which the variants with Gly86 are absolutely required. Thus the naturally occurring alternatives Dw14.2 (Gly86) and Dw14.1 (Val86)--which differ only at this one position in the entire antigen-binding region--show an all-or-nothing difference in presenting activity. This dimorphism at position 86 is widespread, occurring in subtypes of DR1, DR2, DR3, DR5, and DR6 alleles as well as DR4. Since other DR4 subtypes with substitutions at positions 70-74 also fail to present this peptide, and glycine residues can be uniquely flexible, we suggest that this replacement at position 86 acts locally or at a distance by altering the conformation of the peptide-binding cleft. Such profound functional consequences for T-cell recognition as we report here may explain this example of conserved major histocompatibility complex diversity.
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PMID:Critical role for the Val/Gly86 HLA-DR beta dimorphism in autoantigen presentation to human T cells. 171

The mechanism of epileptic seizures so far remains unclear. Immunological disturbances may be one of the possible mechanisms. The assumption that primary epilepsy is an autoimmune disease lacks an experimental basis. In order to search any relationship between generalized epileptic seizures and autoimmune we examined and measured the serum anti-acetylcholine receptor antibody (A AchR Ab) and anti-synaptic premembrane antibody (A PrM Ab) in 12 patients with typical absences, 20 patients with generalized tonic-clonic seizures (GTC) and 6 patients with Lennox-Gastaut Syndrome. 2 (16.7%) out of 12 patients with absences showed positive both A AchR Ab and A PrM Ab, positive A AchR Ab in 1 patient. Among 20 patients with GTC both A AchR Ab and A PrM Ab were positive in 7 patients (35%), A PrM Ab was positive in 1 patient. Totally in 8 patients A PrM Ab was positive. However, the difference between the two Antibodies was not significant (1.1:1). The two kinds of antibody were positive in 5 (83%) out of 6 patients and A PrM Ab was positive, but A AchR Ab was doubtful in another one patient with Lennox-Gastaut syndrome. Therefore, all the patients with Lennox-Gastaut syndrome showed positive antibody. Our data suggested that different types of generalized epileptic-seizures showed different severity of autoimmune dysfunction. The meaning of this kind of immune dysfunction needs further investigation.
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PMID:[Auto-cholinergic synapse dysfunction in patients with generalized epileptic seizures. A preliminary report]. 188 27


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