Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epidermolysis bullosa acquisita (EBA) antigen is type VII collagen that is found within the anchoring fibrils of the basement membrane zone beneath stratified epithelia. Autoimmunity to the EBA antigen/type VII collagen has been associated with three diseases: EBA, bullous systemic lupus erythematosus (SLE) and a subset of linear IgA bullous diseases. Although some systemic diseases in which autoimmunity is thought to play a role (eg, inflammatory bowel disease, thyroiditis) have been reported in association with EBA, so far there have not been systemic diseases associated with autoimmunity to type VII collagen other than SLE. In the case of EBA and bullous SLE, it appears that many patients may have a genetic predisposition toward autoimmunity because they share a human leukocyte antigen (HLA) major histocompatibility (MHC) class II cell surface protein, HLA-DR2. The full clinical spectrum of EBA and perhaps other diseases in which there is an association with autoimmunity to type VII collagen is currently being defined.
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PMID:Autoimmunity to type VII collagen. 193 72

Epidermolysis bullosa acquisita (EBA) is one of a group of primary blistering diseases characterized by dermal/epidermal separation at the basement membrane (BM) of stratified squamous epithelium and IgG anti-BM autoantibodies (ABM). EBA ABMs can be distinguished from IgG ABMs in all other primary blistering diseases by their reactivity with the BM matrix protein, type VII collagen (C-VII). The clinical and histological features of EBA are highly variable and may be indistinguishable from those of other primary bullous diseases. The diagnosis can be confirmed by one of several methods that directly or indirectly demonstrate IgG ABMs to C-VII. IgG ABMs to C-VII are not specific for EBA. They have been described in SLE patients with and without a secondary blistering eruption, bullous eruption of SLE (BSLE). IgA ABMs to C-VII have been described in a subgroup of patients with linear IgA bullous dermatosis. Recent evidence suggests that autoimmunity to C-VII in EBA and BSLE is regulated by the same genes within the major histocompatibility complex (MHC) and contributes to the pathogenesis of acute inflammation and blisters in both disorders. The finding of ABMs to C-VII in SLE and BSLE, evidence that EBA and BSLE share an immunogenetic predisposition to C-VII autoimmunity, and an apparent association between susceptibility to SLE and EBA suggest a close relationship between SLE and autoimmunity to C-VII.
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PMID:Epidermolysis bullosa acquisita: a disease of autoimmunity to type VII collagen. 203 64

Epidermolysis bullosa acquisita (EBA) is a chronic blistering disease characterized by circulating and tissue bound IgG auto-antibodies to the basement membrane zone (BMZ) of stratified squamous epithelium. Recent studies have shown that antibodies recognize epitopes present in the noncollagenous carboxyl-terminal domain of type VII collagen, a BMZ matrix protein. Antibodies with identical specificity also have been detected in patients with the rare blistering disease, bullous systemic lupus erythematosus (bullous SLE), suggesting EBA and bullous SLE are immunologically related diseases. In this study we determined the major histo-compatibility antigen types of 29 EBA patients and 6 patients with bullous SLE. Analysis of the results showed HLA-DR2 was significantly increased in both black EBA patients, P = 0.013 (corrected, RR = 4.8) and white EBA patients, P = 0.0008 (corrected, RR = 13.1). Five of the six bullous SLE patients also were positive for the DR2 antigen, P = 0.009. These results show the expression of autoimmunity to type VII collagen is HLA class II allele associated and that EBA and bullous SLE are immunogenetically related diseases.
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PMID:Increased frequency of HLA-DR2 in patients with autoantibodies to epidermolysis bullosa acquisita antigen: evidence that the expression of autoimmunity to type VII collagen is HLA class II allele associated. 313 69

Autoantibodies to type VII collagen are associated with the blistering diseases epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. We showed previously that these autoantibodies recognize epitopes within the noncollagenous (NC1) region of type VII collagen. That region is composed of fibronectin type III homology units that may contribute to intermolecular cross-linking and basement membrane adhesion functions of type VII collagen. In this study, we defined the specific amino acid sequences recognized by these autoantibodies. By fusion protein analysis, sera from patients with epidermolysis bullosa acquisita and bullous lupus were found to react with two regions within the fourth (E-1) and eighth (E-2) fibronectin homology repeats, each consisting of approximately 100 amino acids. Affinity purification studies showed E-1 and E-2 to be independent and non-cross-reactive epitope regions. These regions were probed further by enzyme-linked immunosorbent assay analysis of overlapping octapeptide sets derived from the amino acid sequences of E-1 and E-2. The results showed two reactive, closely associated octapeptide sequences within each region, both lying in amphipathic portions of fibronectin type III homology repeats. These studies identify short peptide sequences within the NC1 domain of type VII collagen that are targeted independently by autoantibodies. These sequences may play a direct role in determining the properties of type VII collagen that influence adhesion between this molecule and other basement membrane proteins, and their alteration by antibody binding may be the immunopathogenic event underlying epidermolysis bullosa acquisita and bullous lupus.
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PMID:Immunodominant autoepitopes of type VII collagen are short, paired peptide sequences within the fibronectin type III homology region of the noncollagenous (NC1) domain. 753 Feb 71

Blistering in systemic lupus erythematosus has been divided into three groups. A specific subgroup of 'bullous systemic lupus erythematosus' has been defined by Gammon et al. on the basis of a number of criteria. From our experience of seven patients with bullous systemic lupus erythematosus, and after reviewing the literature, we suggest that the current classification is too narrow. Our patients displayed clinical and immunohistological (based on direct and indirect immunofluorescence and Western immunoblotting) heterogeneity. Sera from two patients bound to epidermal epitopes in sodium chloride-split skin, but immunoblotting was negative. In neither of these patients could the target antigen be type VII collagen, the only antigen identified as pathogenic in this disease. Patients with epidermal binding should not be excluded from a diagnosis of bullous systemic lupus erythematosus. SLE is a disease in which there is a genetic predisposition to form antibodies to type VII collagen, along with other autoantibodies, many of which may be implicated in blistering. We suggest that the criteria for the diagnosis of BSLE should be revised. We define this disease as an acquired subepidermal blistering disease in a patient with SLE, in which immune reactants are present at the basement membrane zone on either direct or indirect immunofluorescence.
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PMID:Bullous systemic lupus erythematosus: revised criteria for diagnosis. 766 71

Autoantibodies to type VII collagen are characteristic of the blistering diseases epidermolysis bullosa acquisita and bullous systemic lupus erythematosus (SLE). Blisters in those diseases are due to defective adhesion of the lamina densa subregion of the epithelial basement membrane to the underlying dermis. Previous studies indicating that type VII collagen contributes to lamina densa-dermal adhesion by cross-linking lamina densa and dermal matrix proteins suggests that autoantibodies may contribute to blisters by interfering with type VII collagen function. That hypothesis is supported by previous studies showing autoantibodies from a small number of epidermolysis bullosa acquisita patients recognize proteolytic fragments containing the 145-kD noncollagenous domain of type VII collagen. In this study, we examined reactivity of autoantibodies from a large number of epidermolysis bullosa acquisita and bullous SLE patients with fusion proteins representing most of the noncollagenous domain of type VII collagen and that those regions are homologous to type III repeats of fibronectin. These results suggest autoantibodies binding to fibronectin homology regions within the 145-kD noncollagenous domain may interfere with the adhesion function of type VII collagen and contribute to lamina densa-dermal dysadhesion in epidermolysis bullous acquisita and bullous SLE.
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PMID:Autoantibodies to type VII collagen recognize epitopes in a fibronectin-like region of the noncollagenous (NC1) domain. 768 54

Epidermolysis bullosa acquisita (EBA) is an acquired blistering skin disease characterized by the presence of IgG autoantibodies that recognize type VII (anchoring fibril) collagen. In this study, we have mapped the antigenic epitopes within the type VII collagen alpha chain by Western immunoblotting analysis with sera from 19 patients with EBA, using bacterial collagenase- or pepsin-resistant portions of type VII collagen and a panel of 12 recombinant fusion proteins corresponding to approximately 80% of the primary sequence of the alpha 1 (VII) collagen polypeptide. These studies identified four major immunodominant epitopes localized within the amino-terminal, noncollagenous (NC-1) domain. In addition to EBA, sera from three patients with bullous systemic lupus erythematosus (BSLE) were tested. The pattern of epitopes recognized by these sera were similar to those noted with EBA, suggesting that the same epitopes could serve as autoantigens in both blistering conditions. In contrast, sera from healthy controls or from patients with unrelated blistering skin diseases did not react with type VII collagen epitopes. Collectively, the results indicate that the immunodominant epitopes in EBA and BSLE lie within the noncollagenous regions of type VII collagen. The precise role of the circulating autoantibodies in the pathogenesis of these blistering diseases remains to be elucidated. Conceivably, however, such antibodies could disrupt the assembly of type VII collagen into anchoring fibrils and/or interfere with their interactions with other extracellular matrix molecules within the cutaneous basement membrane zone.
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PMID:Epitope mapping of type VII collagen. Identification of discrete peptide sequences recognized by sera from patients with acquired epidermolysis bullosa. 769 88

We describe a patient with the rare diagnosis of 'Bullous Systemic Lupus Erythematosus'. She is unusual in presenting with classical dermatitis herpetiformis, before the emergence of systemic features. In addition, on indirect immunofluorescence on sodium chloride split skin, there was epidermal binding. Immunoblotting was negative for type VII collagen.
Lupus 1993 Dec
PMID:Bullous systemic lupus erythematosus--a variable disease. 813 23

Bullous systemic lupus erythematosus (SLE) is a rare blistering disease with a distinctive combination of clinical, histologic and immunopathologic features that together constitute a unique bullous disease phenotype. There appear to be at least two immunologically distinct subtypes of bullous SLE characterized by the presence or absence of circulating and/or tissue-bound basement membrane zone autoantibodies that recognize type VII collagen. The two subtypes are not clearly distinguishable except by indirect immunofluorescence and/or direct immunoelectron microscopy. In patients without circulating antibodies, immunoelectron microscopy is required to distinguish between the two subtypes. Patients with autoantibodies to type VII collagen are similar but not identical to patients with epidermolysis bullosa acquisita--another bullous disease associated with autoantibodies to type VII collagen. Autoantibodies to type VII collagen in patients with bullous SLE is only one of several lines of evidence that indicate autoimmunity to that protein and susceptibility to SLE are associated phenomena. In addition, there is emerging evidence for an association between epidermolysis bullous acquisita and SLE. There is also evidence that autoantibodies to type VII collagen are pathogenic in bullous SLE (and epidermolysis bullosa acquisita) and that their production is regulated by the class II major histocompatibility complex DR beta 1 allele, 1501 and possibly other DR beta 1 alleles that share a similar sequence of amino acids in the second hyper-variable region.
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PMID:Bullous SLE: a phenotypically distinctive but immunologically heterogeneous bullous disorder. 842 89

We describe the clinical, histological and immunopathological features of four female patients with the bullous eruption of systemic lupus erythematosus (bullous SLE). Three patients had circulating anti-basement membrane zone (BMZ) antibodies, and Western blot analysis in two cases revealed binding to type VII collagen. Immunoelectron microscopy in one of these patients demonstrated deposition of antibody in the lamina densa and sublamina densa regions, thus sharing immunopathological features with epidermolysis bullosa acquisita (EBA). The vesiculobullous lesions developed 8 months to 6 years after the initial symptoms of SLE, and cleared promptly with dapsone treatment.
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PMID:Bullous eruption of systemic lupus erythematosus: a clinicopathological study of four cases. 847 19


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