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)

Pemphigoid gestationis (PG; herpes gestationis) is a rare autoimmune disease associated with pregnancy, currently defined by the presence of complement deposition along the cutaneous basement membrane zone. It is known to be associated with HLA-DR3 and DR4, and an increase in anti-HLA antibodies in those with a history of PG has been reported. We have studied 39 patients with an immunofluorescence-confirmed diagnosis of PG for the presence and specificity of anti-HLA antibodies. Anti-HLA antibodies were found in all 39 patients. Specificity was against class I antigens in 98% (controls 10%; P < 0.001) and class II antigens in 25% (controls 8.5%; P < 0.001). Almost all anti-HLA antibodies were cytotoxic. The universal presence of anti-HLA antibodies in PG suggests that they may develop coincidently with antibasement membrane antibodies, and may reflect a common immunological event.
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PMID:Anti-HLA antibodies in pemphigoid gestationis (herpes gestationis). 828 21

Pemphigus vulgaris (PV) is an autoimmune disease caused by high concentrations of antibody to an epidermal cadherin. The disease is associated with two kinds of HLA-DR4, DQ8 haplotypes dominantly distributed among Jewish patients, and these plus DR6, DQ5 haplotypes in non-Jewish patients. Low levels of the PV antibody were found in 48% of a total of 120 asymptomatic parents, children, and siblings of 31 patients, thus exhibiting dominant inheritance. The inheritance of these low levels of antibody in asymptomatic relatives was linked to the major histocompatibility complex with a highly significant logarithm of the odds score of 9.07, almost always to a DR4 or DR6 haplotype of the patient. Disease appears to occur in susceptible individuals with low levels of antibody when a second factor, either environmental or genetic, induces high levels, sufficient to produce blisters.
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PMID:Linkage of pemphigus vulgaris antibody to the major histocompatibility complex in healthy relatives of patients. 842 12

Polymorphism is a hallmark of the molecules encoded within the MHC of humans and other mammals. Recently, evidence of polymorphism has also been shown to exist in the transcriptional regulatory regions of HLA-DQB genes. In this article, we report that polymorphism exists also in the promoter region of HLA-DRB genes. The sequence of the regulatory region of DRB genes from five homozygous DR B-cell lines, each of a distinct DR haplotype, revealed a number of differences, some of which are in the critical class II boxes that are generally conserved in class II promoters. The major differences occurred in a comparison of DR4 to the other DR haplotypes. These data suggest the existence of another important source of HLA class II polymorphism that may play a role in susceptibility to HLA-associated autoimmune disease.
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PMID:Polymorphism in the promoter region of HLA-DRB genes. 845 36

Human T-cell-mediated autoimmune diseases are genetically linked to particular alleles of MHC class II genes. Susceptibility to pemphigus vulgaris (PV), an autoimmune disease of the skin, is linked to a rare subtype of HLA-DR4 (DRB1*0402, 1 of 22 known DR4 subtypes). The PV-linked DR4 subtype differs from a rheumatoid arthritis-associated DR4 subtype (DRB1*0404) only at three residues (DR beta 67, 70, and 71). The disease is caused by autoantibodies against desmoglein 3 (DG), and T cells are thought to trigger the autoantibody production against this keratinocyte adhesion molecule. Based on the DRB1*0402 binding motif, seven candidate peptides of the DG autoantigen were identified. T cells from four PV patients with active disease responded to one of these DG peptides (residues 190-204); two patients also responded to DG-(206-220). T-cell clones specific for DG-(190-204) secreted high levels of interleukins 4 and 10, indicating that they may be important in triggering the production of DG-specific autoantibodies. The DG-(190-204) peptide was presented by the disease-linked DRB1*0402 molecule but not by other DR4 subtypes. Site-directed mutagenesis of DRB1*0402 demonstrated that selective presentation of DG-(190-204), which carries a positive charge at the P4 position, was due to the negatively charged residues of the P4 pocket (DR beta 70 and 71). DR beta 71 has a negative charge in DRB1*0402 but a positive charge in other DR4 subtypes, including the DR4 subtypes linked to rheumatoid arthritis. The charge of the P4 pocket in the DR4 peptide binding site therefore appears to be a critical determinant of MHC-linked susceptibility to PV and rheumatoid arthritis.
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PMID:Structural basis for major histocompatibility complex (MHC)-linked susceptibility to autoimmunity: charged residues of a single MHC binding pocket confer selective presentation of self-peptides in pemphigus vulgaris. 852 78

Rheumatoid arthritis (RA), one of the most common autoimmune disorders, is believed to be mediated via. T lymphocytes and genetic studies have shown that it is strongly associated with HLA-DR4. The DR4 subtypes DR4Dw4, DR4Dw14 and DR4Dw15 represent increased risk factors for RA, whereas DR4Dw10 is not associated with the disorder. Our study determines and compares the natural ligand motifs of these MHC class II molecules and identifies 60 natural ligands. At relative position 4 (P4), only the RA-associated DR4 molecules allow, or even prefer, negatively charged amino acids, but do not allow those which are positively charged (Arg, Lys). In the case of DR4Dw10 the preference for these amino acids is reversed. The results predict features of the putative RA-inducing peptide(s). A remarkable specificity, almost exclusively for negative charges (Asp, Glu), is found at P9 of the DR4Dw15 motif. This specificity can be ascribed to amino acid beta57 of the DR beta chain, and gives an important insight into the beta57-association of another autoimmune disease, insulin-dependent diabetes mellitus type I.
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PMID:Natural ligand motifs of closely related HLA-DR4 molecules predict features of rheumatoid arthritis associated peptides. 867 55

Idiopathic Addison's disease (IAD) is a chronic organ-specific autoimmune disease sometimes associated with other autoimmune endocrine diseases. The prevalence is 50-100/million with an incidence of 5-6 cases/million/year. A genetic predisposition to this disease has been reported in subjects with phenotype HLA-DR3, -DR4, -A1, -B8 or HLA-A28, -B8; a phenotype HLA-B8 has been described in subjects with adrenal autoantibodies (AA) not progressing toward an overt disease. There is strong evidence that AA can play a pathogenic role or at least can be considered good immunological markers in IAD. AA may damage adrenal function by a cytotoxic process directed at adrenal cell surface or other intracellular antigens. An antigenic activity has been recently attributed to P450c enzymes and in particular to P450c21. Clinical manifestations of IAD can be preceded by a long period of subclinical adrenocortical impairment, characterized only by the presence of AA with or without adrenocortical function findings. In our experience, where AA titers were 1:8 or higher, progression of adrenal disease was likely with time. A spontaneous remission can indeed occur with lower titers, especially in early stages of subclinical adrenal insufficiency. Finally, a reversal of previously significant AA positive titers in patients in more advanced stages of subclinical adrenal insufficiency seems to be induced by corticosteroid therapy.
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PMID:[Autoimmune Addison's disease. Current knowledge and prospects]. 878 37

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

Rheumatoid arthritis (RA) was one of the first systemic disorders to be considered an autoimmune disease. Two major aspects of RA suggest a fundamental immune-mediated derangement in the disease: (1) presence of often massive lymphocytic infiltrates and activated CD4(+) T cells within the inflamed hypertrophied synovium, and (2) production of large amounts of rheumatoid factor (RF) by B-cells and plasma cells in the involved synovium itself. The actual tissue damage to joints and extra-articular structures affected by the disease comes from the rheumatoid inflammatory pannus or granulomatous collections of cells called rheumatoid nodules. RF production has long been studied as a prime example of apparent autoantibody production in association with the basic underlying disease process. RA patients who belong to subtype HLA DR4, Dw4 (DR B1 or 0401, Dw14 (0404/0408), or Dw15 (0405/0410) are most likely to be seropositive for RF and to have severe progressive disease. RFs are felt to represent an autoantibody associated with RA, since they show principal specificity for structures on the C gamma 3 and C gamma 2 (Fc) domains of IgG. Recent work by our group has defined a number of solvent-exposed linear RF-reactive epitopes on C gamma 3 and C gamma 2 using a strategy of overlapping 7-mers of primary sequence. RFs also have been demonstrated to react with two different regions, SKDWSFY and LSQPKIVKWDR, on beta 2-microglobulin (beta 2m). Many of the RF-reactive sites on C gamma 2 and C gamma 3 as well as on beta 2m show common immunodominant valines, leucines, tryptophanes, arginines, lysines, and glutamines, thus comprising common reactive residues. In the future, this approach may provide more direct insight into the specificities of other autoantibodies.
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PMID:Autoimmune mechanisms involved in the pathogenesis of rheumatoid arthritis. 893 24

Autoimmune hepatitis is a disease of unknown cause. Apart from genetic markers such as HLA DR3 and HLA DR4, female predominance, hypergammaglobulinaemia and characteristic autoantibodies are diagnostic hallmarks. Several viruses have been discussed to induce autoimmune hepatitis, among them all major hepatotropic viruses, Epstein-Barr virus and herpes simplex virus. It seems that herpes viruses may be responsible in at least some cases of patients with autoimmune hepatitis type 2. Furthermore, hepatotropic viruses like hepatitis C and hepatitis D virus may cause autoimmune phenomena which are similar to those in idiopathic autoimmune hepatitis. LKM-1 antibodies in hepatitis C and LKM-3 antibodies in hepatitis D may cause diagnostic problems. LKM-1 antibodies in hepatitis C are directed either against cytochrome P450 2D6 or other yet unidentified microsomal antigens. As in hepatitis C the antimicrosomal autoantibody response in hepatitis D is more heterogeneous. These LKM-3 antibodies react with several epitopes on proteins of family 1 and 2 UDP-glucuronosyltransferases (UGT). Additional autoantibodies are seen in hepatitis D virus infection. Liver diseases are models to study autoimmune disease, drug-induced and virus-induced autoimmunity in humans.
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PMID:Hepatotropic viruses and autoimmunity 1997. 909 72

The role of peptides in determining immune responses for both allorecognition and antigen-specific recognition has been clearly documented. The importance of different regions of the major histocompatibility complex (MHC) class II molecule in contributing to recognition has been demonstrated by studies involving site-directed mutagenesis and exon shuffling. These studies have indicated that the N-terminal region of the MHC class II molecule has a role to play in contributing to the T-cell receptor (TCR)-MHC-peptide interaction. Variation in the importance of different regions of the MHC class II molecule may be dependent on different aspects of this interaction, such as restriction specificity and affinity of the responding T-cell clone, and the nature of the bound peptide. We demonstrate here that the degree of T-cell degeneracy may be allele dependent. Thus, a series of exon-shuffled molecules were generated by shuffling the first and second variable region of a particular DR beta 1 molecule with the third variable region of a different DR beta 1 molecule. A panel of transfectants, which expressed these hybrid molecules, was then generated and used as antigen-presenting cells (APCs). A panel of peptide-specific T-cell clones was generated using the native HLA-DR molecules as the restricting elements. For the majority of restricting alleles, HLA-DRB5*0101, HLA-DRB1*1101, and HLA-DRB1*0701, all three variable regions were required for recognition. The exception to this observation was HLA-DRB1*0401, which was degenerate. Such degeneracy may facilitate the breakdown of self-tolerance through the cross-reactive recognition of other alleles in DR4/DR"x" heterozygotes. Such an observation as this may contribute to our understanding of the etiopathology of rheumatoid arthritis, an autoimmune disease strongly associated with HLA-DRB1*0401.
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PMID:Allele-specific variation in the degeneracy of major histocompatibility complex (MHC) restriction. 915 54


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