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)

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system (CNS). Studies have shown that the encephalitogen responsible for EAE is the basic protein (BP) found inCNS myelin and is, perhaps, the only encephalitogenic component of the CNS. Purified lipophilin, a hydrophobic lipoprotein of myelin, was tested for its ability to induce EAE in guinea pigs. Animals challenged with myelin lipophilin (in CFA) developed clinical and histological signs of EAE which were indistinguishable from those developed by animals challenged with myelin BP (in CFA). Both lipophilin and BP induced and elicited delayed type hypersensitivity in animals challenged with either antigen and the development of delayed type hypersensitivity correlated with eventual onset of clinical signs of disease. The absence of BP from the lipophilin preparation used in this study was documented by several purification procedures and chemical modification of tryptophan in lipophilin, destroyed its ability to induce EAE. These results demonstrate that myelin lipophilin is encephalitogenic and induces a cell-mediated immune disease of the CNS similar, if not identical, to BP-induced EAE. Tryptophan, which is known to be an essential residue in the BP-determinant for disease in guinea pigs, is required for the encephalitogenic activity of lipophilin.
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PMID:Myelin lipophilin-induced experimental allergic encephalomyelitis in guinea pigs. 615 58

In experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139-151, we have previously shown that the disease is mediated by Th1 cells, which recognize tryptophan 144 as the primary TCR contact point. Here we describe an altered peptide ligand (APL), generated by a single amino acid substitution (tryptophan to glutamine) at position 144 (Q144), which inhibits the development of EAE induced with the native PLP 139-151 peptide (W144). We show that the APL induces T cells that are cross-reactive with the native peptide and that these cells produce Th2 (IL-4 and IL-10) and Th0 (IFN gamma and IL-10) cytokines. Adoptive transfer of T cell lines generated with the APL confer protection from EAE. These data show that changing a single amino acid in an antigenic peptide can significantly influence T cell differentiation and suggest that immune deviation may be one of the mechanisms by which APLs can inhibit an autoimmune disease.
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PMID:An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis. 758 31

Autoimmune diseases may be induced by physical and/or chemical environmental factors. A review of the available literature on mercuric chloride, iodine, silicone, anilides, L-tryptophan, vinyl chloride, and canavanine suggests three general mechanisms by which they may induce disease. First, oxidative damage probably is a frequent process involved in disease induction and pathogenesis. Second, certain compounds also may generate antigen-specific immune responses that could then cross-react with self-tissues. Other xenobiotics might bind to self-tissues and increase self-tissue immunogenicity. Third, physical and chemical agents may also modulate the immune system. Finally, in response to controversies surrounding the influence of human activities on global climate changes, the immunosuppressive effects of ozone and ultraviolet radiation are discussed.
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PMID:Autoimmunity and selected environmental factors of disease induction. 834 47

The cause of toxic oil syndrome (TOS) has not yet been definitively determined, but some genetic susceptibility factors (certain HLA antigens and female sex) have been identified in 236 patients. Similarities with genetic factors for scleroderma and hydralazine-induced lupus (i.e. in TOS female sex and HLA-A24, Pcorrected = 0.00001 and DR4, Pcorrected = 0.04, respectively) may provide a clue to the responsible xenobiotic and its pathogenesis, and may also help in understanding the basis of the related eosinophilia-myalgia syndrome associated with tryptophan ingestion. In this paper it is also established that a human class I antigen (HLA-A24) and, independently, an HLA class II haplotype (DR4-DQ8, Pcorrected = 0.04) and arginine 52 in the alpha-DQ chains (Pcorrected = 0.03) are associated with TOS susceptibility, similarly to insulin-dependent diabetes. This further supports the classification of TOS as an autoimmune disease. Also, the increased frequency of a particular set of low-frequency HLA class I antigens in chronic TOS patients (i.e. B27, B37, B38 and B49) and the probable decrease in the frequency of HLA-B homozygotes in surviving patients (Pcorrected = 0.008) may provide an objective model to explain the maintenance of the HLA polymorphism: less frequent HLA alleles may be more advantageous in the event of unexpected human contact with unusual xenobiotics (not only microbes); however, other mechanisms working together to preserve and generate HLA polymorphism may coexist.
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PMID:Frequencies of HLA-A24 and HLA-DR4-DQ8 are increased and that of HLA-B blank is decreased in chronic toxic oil syndrome. 880 34

While it has been demonstrated that such low-molecular-weight cyclic silicones as octamethylcyclotetrasiloxane (D4) exhibit adjuvant activity, the mechanism of immunological response to silicone is still not clear. This study therefore used fluorescence and circular dichroism (CD) spectroscopy to investigate the denaturation and conformational change of two proteins, fibronectin (Fn) and fibrinogen (Fbg), induced by D4 in vitro. Incubating D4 with Fbg or Fn at D4-to-protein ratios of > 100 or for > 10 h yielded white and mould-like precipitates of the proteins, indicating massive denaturation and aggregation. The fact that the decrease in fluorescence intensity of D4-treated Fn and Fbg was accompanied by a red shift in the maximum wavelength also indicated that denaturation of the proteins had taken place. These changes in fluorescence might result from exposure of tryptophan residuals in the proteins to polar water molecules inasmuch as the denaturation would lead to changes in the tertiary structures of the proteins and rearrangement of the tryptophan residues. The loss of the tertiary structure leads to protein denaturation and, consequently, precipitation. The difference in CD spectra between control Fbg (or Fn) and D4-treated Fbg (or Fn) indicated conformational changes of the proteins when incubated with D4. Thus it has been demonstrated that D4 can induce denaturation and conformational changes in Fbg and Fn and it can be expected that protein molecules that have undergone denaturation or conformational change induced by D4 may act as antigens and stimulate the immune system to generate antibodies, ultimately resulting in autoimmune disease.
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PMID:Protein denaturation induced by cyclic silicone. 961 6

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction caused by antibodies against the nicotinic acetylcholine receptor (AChR-Ab). We report a 16-year-old girl with severe MG who showed a poor response to plasma exchange and tryptophan-linked polyvinylalcohol gel immunoadsorption. Further improvement of muscle strength and decline of AChR-Ab could be achieved after initiation of protein-A immunoadsorption (PA-IA). Maintenance therapy with PA-IA and intravenous pulses of cyclophosphamide resulted in a stabilisation of the disease, with a complete remission during the follow-up period of six months. We suggest that PA-IA may be valuable and safe in the management of patients with severe MG, and maintenance therapy with PA-IA and cyclophosphamide may prevent serious and potentially life-threatening relapses of the disease.
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PMID:Treatment of severe myasthenia gravis with protein A immunoadsorption and cyclophosphamide. 1017 93

A large number of drugs and an increasing number of environmental agents reportedly result in the appearance of a number of autoantibodies and in many instances in the appearance of a range of autoimmune clinical syndromes. The major disorders so recognized have marked resemblances to the autoimmune disease systemic lupus erythematosus. The commonly used term is drug-induced lupus; a better term is drug-related lupus. There is considerable interest at the present time in an increasing number of environmental agents. There have been two epidemics in recent years--one in Spain to a contaminant of rapeseed oil and one in the United States to a contaminant of l-tryptophan that caused an eosinophilic myositis. It is important for physicians and others involved in health care to recognize the potential associations of these diseases of unknown cause or causes.
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PMID:Are there environmental forms of systemic autoimmune diseases? 1050 35

Environmental and other xenobiotic agents can cause autoimmunity. Examples include drug-induced lupus, toxic oil syndrome, and contaminated l-tryptophan ingestion. Numerous mechanisms, based on (italic)in vitro(/italic) evidence and animal models, have been proposed to explain how xenobiotics induce or accelerate autoimmunity. The majority of these can be divided into three general categories. The first is those inhibiting the processes involved in establishing tolerance by deletion. Inhibiting deletion can result in the release of newly generated autoreactive cells into the periphery. The second mechanism is the modification of gene expression in the cells participating in the immune response, permitting lymphocytes to respond to signals normally insufficient to initiate a response or allowing the antigen-presenting cells to abnormally stimulate a response. Abnormal gene expression can thus disrupt tolerance maintained by suppression or anergy, permitting activation of autoreactive cells. The third is the modification of self-molecules such that they are recognized by the immune system as foreign. Examples illustrating these concepts are presented, and related mechanisms that have the potential to similarly affect the immune system are noted. Some mechanisms appear to be common to a variety of agents, and different mechanisms appear to produce similar diseases. However, evidence that any of these mechanisms are actually responsible for xenobiotic-induced human autoimmune disease is still largely lacking, and the potential for numerous and as yet unidentified mechanisms also exists.
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PMID:Environmentally induced autoimmune diseases: potential mechanisms. 1050 39

The pattern of contaminants in pharmaceutical and feed grade L-tryptophan (Trp) was investigated in a market survey of 22 lots of 6 different manufacturers. To date, 5 case associated contaminants in Showa Denko tryptophan (SD-Trp) known to cause the autoimmune disease eosinophilia-myalgia syndrome (EMS) have been structurally elucidated: 3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrroloindole-2-carboxylic acid (PIC), an indoline compound, is one of the most abundant degradation compounds of unbound Trp during oxidative treatment. 2-(3-indolylmethyl)-L-tryptophan (IMT) and 2-(2-hydroxyindoline)-tryptophan (HIT) are both 2-substituted Trp-derivatives. IMT was synthesized by the reaction of Trp and indole-3-methanol or indole-3-acetaldehyde, respectively. From this finding it is proposed that Trp-metabolites can decompose under formation of transitional, mesomerism-stabilized cations that react with excess Trp to yield 2-substituted Trp derivatives. The decomposition of Trp-metabolites could be induced by elevated or low pH-values that occur during the downstream processing of the Trp fermentation broth. IMT was detected in pharmaceutical-grade and feed-grade Trp in amounts of < 20-1,400 mg/kg. 1,1'-Ethylidenebis-(L-tryptophan) (EBT) is formed from acetaldehyde and Trp under acidic conditions and serves as a marker for EMS-suspicious Trp. 3-(Phenylamino)alanine (PAA) is the only not Trp derived case associated contaminant. Low amounts of PAA (20 mg/kg) could be detected in feed-grade Trp of one manufacturer. Non-EMS correlated 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acids of Trp and formaldehyde, acetaldehyde and indole-3-acetaldehyde could be detected in the examined Trp raw materials (< 10-13,500 mg/kg). In order to guarantee the safety of Trp containing drugs the amount of EBT (< 10 mg/kg Trp) and the sum of UV220 nm detectable contaminants (< 400 mg/kg Trp) are limited by the European authorities.
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PMID:Synthesis, formation, and occurrence of contaminants in biotechnologically manufactured L-tryptophan. 1072 Oct 90

Systemic lupus erythematosus (SLE), a progressive autoimmune disorder, is associated with chronic stimulation of various components of the immune system. Since cell-mediated immunity is also activated, we were interested to test for abnormalities in tryptophan metabolism in SLE which may result from activation of indoleamine 2,3-dioxygenase by cytokines released during the immune response. We measured serum tryptophan and kynurenine concentrations in 52 patients with SLE as well as serum neopterin as an indicator for the degree of immune activation. Compared to controls, we found significantly decreased tryptophan and increased kynurenine concentrations in SLE. The extent of tryptophan catabolism correlates with neopterin concentrations or with the disease activity index. Tryptophan depletion may be associated with neurologic/psychiatric disturbances in patients suffering from SLE.
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PMID:Degradation of tryptophan in patients with systemic lupus erythematosus. 1072 Nov 2


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