Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deposits of IgG localized to collagen bundles/extracellular matrix components occurred in skin biopsies from patients with primary fibromyalgia (PF). None of these patients demonstrated a positive lupus band test. Control skin biopsies from healthy controls were negative but showed intense reactivity for IgG after collagenase treatment. PF-skin attached both homologous and heterologous serum IgG in indirect immunofluorescence, which may point to a qualitative alteration of dermal matrix components in PF. Skin from patients with systemic lupus erythematosus and rheumatoid arthritis showed a lower dermal fluorescence intensity than in PF patients. The cause of the presence of IgG in dermal tissue from PF patients is unclear. It may be caused by a non-specific attachment of IgG to the extracellular matrix related, for example, to tissue hypoxia and/or increased capillary leakage due to an increased number of mast cells in the PF-skin.
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PMID:Attachment of IgG to dermal extracellular matrix in patients with fibromyalgia. 215 58

Preparations of human glomerular basement membrane (GBM) were digested with collagenase, and a Goodpasture (GP) antigen rich pool from gel filtration column runs was identified by antibody inhibition radioimmunoassay. The components of the GP antigen pool were separated on polyacrylamide gels, and transferred to nitrocellulose sheets by the 'western' blotting technique. The blots were separately reacted with thirteen GP sera as primary antibody, followed by peroxidase labelled goat anti-human IgG and revealed 45-50K (two bands) and 25-28K (one-three bands) components. No corresponding reactivity was observed using convalescent GP sera or other control sera (normal human serum, rapidly progressive glomerulonephritis with or without pulmonary haemorrhage, and lupus erythematosus) as primary antibody.
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PMID:Detection of Goodpasture antigen in fractions prepared from collagenase digests of human glomerular basement membrane. 631 59

Peripheral blood mononuclear cells from patients with rheumatoid arthritis (n = 27), systemic lupus erythematosus (n = 24), juvenile rheumatoid arthritis (n = 30), osteoarthritis (n = 20), apparently healthy adults (n = 12), and nonarthritic children (n = 8) were exposed to several putative connective tissue antigens to determine if the monokine, mononuclear cell factor, was released. Release of this factor was detected by bioassay in which enhancement of collagenase production from human synovial cells or dermal fibroblasts was measured. The antigens, all of homologous tissue origin, included cyanogen bromide-derived peptides of type I, II, and III collagens, type I and II helical collagens, and cartilage proteoglycan. Of the subjects examined, 44% of the rheumatoid group, 42% of the systemic lupus group, 33% of the juvenile rheumatoid group but only 10% of the osteoarthritic group and 5% of the control group released monokine after exposure of peripheral blood mononuclear cells to at least one of these connective tissue antigens. Patients with rheumatoid arthritis most frequently responded to type II peptides (but not to type II helical collagen) although the frequencies of responses to type I peptides, type I helical collagen and proteoglycan were also elevated over levels observed in the control population. Positive responses in these patients typically occurred to only one antigen, were transient, often occurred close to the onset of arthritis, and appeared to be unrelated to disease activity. The profiles of responses in patients with juvenile rheumatoid arthritis and systemic lupus shared many features in common and were distinct from those of adult rheumatoid arthritis. Patients with systemic lupus or juvenile rheumatoid arthritis responded to all of the antigens tested. Positive responses often occurred simultaneously to several antigens. Responses to type II helical collagen were most common while sensitization to type II peptides was infrequently detected. Positive responses were transient, unrelated to overall disease activity, type of juvenile arthritis, or duration of disease in lupus patients. Stimulation of mononuclear cell factor release by connective tissue molecules and their degradation products may make an important contribution to the chronic inflammation commonly seen in these diseases.
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PMID:Connective tissue antigens stimulate collagenase production in arthritic diseases. 632 85

To clarify the pathogenesis of lupus nephritis, we developed an assay that defines a glomerular binding activity (GBA) in both murine and human lupus sera highly correlated with nephritis. In the current study, we used a cross-adsorption strategy to establish that the GBA in MRL lpr serum binds to the glomerular basement membrane (GBM). We subsequently observed that this binding to the GBM was competitively inhibited by either exogenous DNA or histone, abrogated by pretreatment of the GBM with DNAse, and restored after DNase treatment with DNA/histone in a synergistic fashion. GBM binding was also completely inhibited by pretreatment of GBM with collagenase but not heparatinase. The effect of collagenase was not reversed by the subsequent addition of DNA, but was restored by the sequential re-addition of type IV collagen and DNA. By using purified basement membrane components, we found that MRL lpr serum bound avidly to DNA coated on type I collagen but less well (or not at all) to DNA coated on type IV collagen, laminin, or fibronectin. Histone pretreatment of type IV collagen before DNA addition, however, synergistically enhanced binding in a fashion similar to that seen with native GBM. Thus, the GBA in MRL lpr serum seems to be comprised of autoantibodies that bind to histones and/or DNA that adhere to type IV collagen within the GBM. These data support the planted Ag hypothesis as the principal pathogenic mechanism in lupus nephritis and suggest that multiple autoantibodies may contribute to this disorder.
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PMID:Glomerular binding activity in MRL lpr serum consists of antibodies that bind to a DNA/histone/type IV collagen complex. 786 8

Irreversible congenital heart block (CHB) and the transient rash of neonatal lupus are strongly associated with maternal antibodies to SSA/Ro and SSB/La proteins; however, the precise mechanism by which these antibodies mediate organ-specific injury is not yet defined. Culturing of keratinocytes has provided critical insights. Accordingly, successful culturing of human fetal cardiac myocytes at high yield would constitute a powerful tool to directly examine conditions that promote expression of the target autoantigens. To accomplish this aim, fetal cardiac myocytes from 18- to 22-wk abortuses were established in culture using a novel technique in which cells were isolated after perfusion of the aorta with collagenase in a Langendorff apparatus. After preplating to decrease fibroblast contamination, cardiocytes were grown in flasks and slide chambers. Staining with monoclonal anti-sarcomeric alpha-actinin revealed the expected striations typical of cardiac myocytes in 70-90% of the cells after 4 d in culture. Furthermore, the cells were observed to beat at rates varying between 25-75 beats per minute (bpm) after the addition of 1.8 mM CaCl2. An average yield of 45-60 x 10(6) cells was obtained from a 3- to 5-g heart. Cellular localization of SSA/Ro and SSB/La by indirect immunofluorescence and demonstration of mRNA expression by reverse transcriptase polymerase chain reaction supports the feasibility of cultured cardiac myocytes for the study of congenital heart block. In contrast to the increased expression of SSA/Ro reported for keratinocytes, incubation of cultured human cardiac myocytes with either 17beta-estradiol or progesterone did not alter mRNA expression or cellular localization of 48 kD SSB/La, 52 kD SSA/Ro, or 60 kD SSA/Ro. In summary, we describe a novel method to successfully culture human fetal cardiac myocytes that should provide a valuable resource for investigation of the molecular mechanism(s) contributing to the development of congenital heart block. Differential constitutive and estradiol-induced expression of 52 and 60 kD SSA/Ro in human cardiac myocytes compared with keratinocytes may be a factor contributing to the marked discordance of clinically detectable injury in these two target tissues.
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PMID:mRNA and protein expression of SSA/Ro and SSB/La in human fetal cardiac myocytes cultured using a novel application of the Langendorff procedure. 1002

Phenytoin (diphenylhydantoin or Dilantin) is a highly effective and widely prescribed anticonvulsant agent used in the treatment of grand mal and psychomotor epilepsy. In dermatology, phenytoin has been used to treat ulcers, epidermolysis bullosa, and inflammatory conditions. Its mechanism appears to involve its ability to inhibit collagenase. Its topical use for the promotion of wound healing seems promising but requires further trials. The side effects of phenytoin continue to create significant morbidity. Common side effects include gingival hyperplasia, coarsening of the facies, and hirsutism. Rarer cutaneous side effects include drug-induced lupus, purple-hand syndrome, pigmentary alterations, and IgA bullous dermatosis. It can cause generalized cutaneous eruptions that include a maculopapular exanthem, Stevens-Johnson syndrome, generalized exfoliative dermatitis, toxic epidermal necrolysis, vasculitis, and fixed-drug eruptions. Phenytoin is linked to a hypersensitivity syndrome manifested by fever, rash, and lymphadenopathy. Patients receiving phenytoin may develop pseudolymphoma or, rarely, malignant lymphoma and mycosis-fungoides-like lesions. Phenytoin can effect clotting function. Phenytoin can alter vitamin and mineral levels. Prenatal exposure to phenytoin may result in a spectrum of structural, developmental, and behavioral changes known as the fetal hydantoin syndrome. After 60 years of use, phenytoin uses and mechanisms of action have yet to be fully defined; the drug remains a useful tool and an important subject for additional research.
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PMID:Phenytoin in cutaneous medicine: its uses, mechanisms and side effects. 1295 53

MRL/Mp mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop polyarthritis, sialoadenitis and dacryoadenitis, resembling rheumatoid arthritis (RA), and also corneal involvement such as keratopathy and scleritis, which is a major complication in RA patients. In this study, we found that the expression levels of IL-1beta and MMP-1 mRNAs in cornea were high in both MRL/lpr and MRL/Mp-+/+ strains of mice at an age younger than when they develop any inflammatory lesions. This was not true of other inbred strains, even those bearing the lpr gene, and also not of (NZB x NZW) F1 lupus mice. There was no significant difference in the expression of IL-1alpha and TGFbeta in cornea in these strains. Using crosses between MRL/lpr and C3H/HeJ-lpr/lpr (C3H/lpr) mice, at least the expression of IL-1beta was found to be under the control of the MRL genetic background, likely with a recessive mode of inheritance. Considering that IL-1beta in cornea was detected particularly in the epithelial layer, the high expression of IL-1beta in cornea is most likely involved in the genetic predisposition for corneal involvement and possibly also for arthritis in an MRL strain of mice.
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PMID:High expression of interleukin-1beta in the corneal epithelium of MRL/lpr mice is under the control of their genetic background. 1508 86

Interactions between members of the TNF ligand superfamily with their cognate TNF receptors play a crucial role in maintaining immune homeostasis in normal individuals, while dysregulation of certain TNF-ligands and receptors contributes to the pathogenesis of autoimmunity. Identification of novel members of the TNF ligand and receptor families will promote our understanding of the pathogenesis of systemic autoimmune diseases, thus facilitating the development of novel therapeutic approaches. TNF-like weak inducer of apoptosis (TWEAK), a recently identified member of the TNF ligand family, induces PGE2, MMP-1, IL-6, IL-8, RANTES, and IP-10 in fibroblasts and synoviocytes, and upregulates ICAM-1, E-selectin, IL-8, and MCP-1 in endothelial cells. The receptor for TWEAK, Fn14, is expressed in various organs including the kidney; it is intriguing that some of these chemokines induced by TWEAK are crucial in the pathogenesis of lupus nephritis. Furthermore, others have described upregulated TWEAK expression on the surface of T cells in human lupus. In this paper we review the possible roles of TWEAK/TWEAK receptor interactions in the pathogenesis of inflammatory and systemic autoimmune diseases, with particular focus on systemic lupus erythematosus. TWEAK blockade may be helpful therapeutically in restoration of tolerance, but is more likely to modify inflammatory damage in target organs.
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PMID:The role of TWEAK/Fn14 in the pathogenesis of inflammation and systemic autoimmunity. 1535 86

Anti-glomerular basement membrane (anti-GBM) disease is an aggressive form of glomerulonephritis, usually mediated by immunoglobulin G (IgG) autoantibodies to the noncollagenous (NC1) domain of alpha 3(IV) collagen. Less is known about the target antigen(s) in patients with atypical anti-GBM disease involving IgA autoantibodies. We report a new case of IgA anti-GBM disease in a patient with a history of proliferative lupus nephritis who presented with increasing creatinine levels, proteinuria, and hematuria, but no clinical or serological evidence of lupus recurrence. Renal biopsy showed focal and segmental necrotizing glomerulonephritis with strong linear capillary loop IgA staining by means of immunofluorescence. Serological test results were negative for IgG or IgA autoantibodies against the alpha 3NC1 domain. By means of immunoblotting, IgA from patient serum bound to 38- to 48-kd antigens collagenase-solubilized from human GBM, but not to purified NC1 domains of GBM collagen IV. The target of patient's IgA autoantibodies thus was identified as a novel GBM antigen, distinct from the alpha 3NC1 domain or other known targets of anti-GBM IgA autoantibodies. Clinical resolution was attained by means of conventional treatment with steroids and cyclophosphamide. The diversity of antigens recognized by anti-GBM IgA autoantibodies highlights the importance of renal biopsy for the reliable diagnosis of this rare condition because conventional serological immunoassays likely would yield false-negative results.
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PMID:Antigenic heterogeneity of IgA anti-GBM disease: new renal targets of IgA autoantibodies. 1875 76

Anti-apolipoprotein A-1 (anti-apoA-1 IgG) and anti-double stranded DNA (anti-dsDNA IgG) autoantibodies have been described as mediators of atherogenesis in mice and humans. In the present study, we aim to investigate the association between atherosclerotic parameters, autoantibodies and plaque vulnerability in the context of systemic lupus erythematosus (SLE). We therefore bred a lupus prone-mouse model (Nba2.Yaa mice) with Apoe-/- mice resulting in Apoe-/-Nba2.Yaa mice spontaneously producing anti-apoA-1 IgG antibodies. Although Apoe-/-Nba2.Yaa and Apoe-/- mice subject to a high cholesterol diet displayed similar atherosclerosis lesions size in aortic roots and abdominal aorta, the levels of macrophage and neutrophil infiltration, collagen, MMP-8 and MMP-9 and pro-MMP-9 expression in Apoe-/-Nba2.Yaa mice indicated features of atherosclerotic plaque vulnerability. Even though Apoe-/-Nba2.Yaa mice and Apoe-/- mice had similar lipid levels, Apoe-/-Nba2.Yaa mice showed higher anti-apoA-1 and anti-dsDNA IgG levels. Apoe-/-Nba2.Yaa mice displayed a reduction of the size of the kidney, splenomegaly and lymph nodes (LN) hypertrophy. In addition, anti-apoA-1 and anti-dsDNA IgG increased also in relation with mRNA levels of GATA3, IL-4, Bcl-6 and CD20 in the spleen and aortic arch of Apoe-/-Nba2.Yaa mice. Our data show that although atherosclerosis-lupus-prone Apoe-/-Nba2.Yaa mice did not exhibit exacerbated atherosclerotic lesion size, they did show features of atherosclerotic plaque destabilization in correlation with the increase of pro-atherogenic autoantibodies.
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PMID:Atherosclerotic plaque vulnerability is increased in mouse model of lupus. 3311 Jan 93


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