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)

The expression of the heterodimeric complex of the calcium-binding proteins MRP-8 and MRP-14 was investigated in various inflammatory dermatoses using immunohistochemical staining with the monoclonal antibody 27E10. In addition to the inflammatory infiltrate, a positive staining was repeatedly found in the involved epidermis from patients with lichen planus, lupus erythematosus and psoriasis vulgaris, but not in normal skin epidermis and/or in epidermis from leucocytoclastic vasculitis patients. The keratinocytic expression of the 27E10 antigen was dissimilar to that of the MHC class-II molecules and the adhesion molecule ICAM-1. These data indicate that the 27E10 antigen is a distinct activation marker of inflammatory keratinocytes and may have proinflammatory properties.
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PMID:Epidermal expression of the calcium binding surface antigen 27E10 in inflammatory skin diseases. 128 18

Immunologic cytotoxicity is an important endpoint of the immune response to tumors, viral infected cells, grafted tissues, and exogenous microorganisms, and is also an important mechanism of disease, especially in autoimmunity. There are multiple mechanisms of immunologic cytotoxicity, but each has three major stages: leukocyte/target attachment, specific recognition, and target lysis following effector activation. Adhesion molecules present on leukocytes and potential targets appear to be involved in all three stages of cytotoxicity. A major factor in all types of cellular cytotoxicity is the interaction of LFA-1 on leukocytes and CAM-1 on targets. Modulation of ICAM-1 levels on target by the cytokines TFN-g, IL-1, and TNF-a is a major point of control of the susceptibility of targets to cytotoxicity by many different cytotoxic mechanisms. It also appears that modulation of the avidity of LFA/ICAM-1 binding is another important control point in modulating immunologic cytotoxicity. Cytokines also have important effects on immunologic cytotoxicity in ways other than adhesion molecule induction: effector priming to better respond to specific recognition signals, effector mobilization into tissue, and expansion of cytotoxic effector populations. ICAM-1 on the surface of epidermal keratinocytes and melanocytes is likely to greatly influence cytotoxic damage of these cells in diseases as photosensitive lupus erythematosus, lichen planus, erythema multiforme, and vitiligo. It has been found that the epidermal staining pattern for ICAM-1 in each of these diseases in distinctive and different in each disease. It is proposed that disease-specific induction of ICAM-1 by factors such as UVR and herpes-virus is an important determinant in triggering these skin diseases and in determining the pattern of disease.
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PMID:Cytokine modulation of adhesion molecules in the regulation of immunologic cytotoxicity of epidermal targets. 225 27

We found distinct patterns of intercellular adhesion molecule-1 (ICAM-1) expression in three diseases characterized by interface dermatitis with mononuclear infiltrates and keratinocyte cytotoxicity: lichen planus (LP), subacute cutaneous lupus erythematosus (SCLE), and erythema multiforme (EM). In LP, basal keratinocytes show strong ICAM-1 expression associated with a dermal infiltrate, but ICAM-1 expression in the rest of the epidermis is minimal. In SCLE, there is diffuse epidermal ICAM-1 expression, sometimes with accentuation on the cell surface of basal cells. In EM, there is strong basal cell expression of ICAM-1 with evident cell surface accentuation, and also pockets of suprabasal expression with cell surface accentuation. These patterns are associated with different factors that trigger cytokine release in different locations. Both tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) produce greater relative ICAM-1 expression in basal keratinocytes than in more differentiated keratinocytes. In LP, the pure basal keratinocyte expression of ICAM-1 appears to be caused by cytokines, predominantly IFN-gamma, released by dermal lymphocytes. The pattern of ICAM-1 in SCLE corresponds to the pattern induced by ultraviolet radiation (UVR): diffuse epidermal ICAM-1 expression, sometimes with basal accentuation. Some individuals are "responders" to TNF-alpha or UVR, showing high levels of ICAM-1 expression following UVR or TNF-alpha stimulation in vitro or UVR stimulation in vivo. We propose that the pattern of ICAM-1 induction in SCLE is dependent on UVR-induced TNF-alpha release. EM is associated with apparent latent Herpes simplex virus, and Herpes simplex virus (HSV)-infected keratinocytes show enhanced ICAM-1 expression. We propose that in EM suprabasal ICAM-1 expression may be induced directly by HSV infection or indirectly through TNF-alpha release induced by HSV reactivation. Induction of ICAM-1 within the epidermis is stratified and individually variable. Basal keratinocytes show maximal induction of ICAM-1 expression due to innate sensitivity to TNF and IFN-gamma stimulation, and to location adjacent to dermal sources of cytokines. Suprabasal ICAM-1 can be induced by UVR and epidermal TNF-alpha release, and by factors such as viral infection. Different triggers of cytokine release and adhesion molecule induction may influence the different patterns of inflammation seen in diverse inflammatory skin diseases.
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PMID:In three types of interface dermatitis, different patterns of expression of intercellular adhesion molecule-1 (ICAM-1) indicate different triggers of disease. 761 1

Lupus erythematosus (LE) was first described as a clinical dermatological entity in 1851. The possibility of serious systemic manifestations became recognized by 1872 as the result of the work of M. Kaposi. Since then, it took a long time before LE was recognized to be an immunological disease. Recognition of antinuclear antibodies and their deposition at the basal membrane region in skin resulted in two concepts of LE pathogenesis. In one, antibody complexing and complement activation with generation of the membrane attack complex (C5-C9) is thought to be the origin of the chronic inflammatory reaction. In the other, antibody deposition enables antibody dependent cellular cytotoxicity, leading to hydropic degeneration of the basal epidermal layer and subsequent chronic inflammation. Norris postulated in 1993, that the epidermis acts as a pro-inflammatory organ, in which an UVB-induced increase in cytokine production is followed by increased expression of adhesion molecules on keratinocytes as well as dermal endothelial cells. Translocation of certain antigens (i.e. Ro & La) to which circulating auto-antibodies exist in LE, enables recognition by adhesion molecule directed skin-invading T cells with subsequent cytotoxic effector activity. A persistent chronic inflammatory reaction then ensues. A similar development in knowledge may be seen in the history of immunodermatology. Originally, lupus erythematosus could not be recognized as an immune disease, since concepts of immunology were virtually non-existent when LE was first described. Immunology, In the first half of this century, was mainly antibody-oriented and thus came the concept of (S)LE as an antibody-mediated disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The skin immune system: lupus erythematosus as a paradigm. 772 32

The expression of adhesion molecule Leukocyte Function Antigen-1 (LFA-1) on peripheral blood leukocytes was evaluated (using a monoclonal antibody anti CD11a/LFA-1) in 52 spondylarthropathies (SA) (35 HLA B27 positive), 12 healthy patients, 24 active rheumatoid arthritis (RA) and 12 systemic lupus (SLE) patients. LFA-1 expression on lymphocytes was similar in the different groups of patients, but LFA-1 expression on granulocytes was higher in SA than in controls (p < 0.05) or in RA or SLE. Fluorescence intensity of anti LFA-1 staining on SA granulocytes correlated with serum IgA levels. There was no difference between HLA B27 positive/negative, biologically inflammatory (CRP > 21 mg/l)/non inflammatory SA patients. This study seems to confirm the granulocyte and IgA involvement in immunopathogenesis of spondylarthropathies.
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PMID:[Leukocyte expression of the LFA-1 adhesion molecule in spondylarthropathies]. 800 Mar 97

This review discusses the mechanisms involved in different photosensitive lupus syndromes: acute cutaneous lupus erythematosus, chronic cutaneous (discoid) lupus erythematosus, subacute cutaneous lupus erythematosus, and neonatal lupus erythematosus. It is proposed that there are three principal determinants of photosensitivity in lupus: 1) susceptibility to UVR-induced release of epidermal and dermal cytokines; 2) susceptibility to UVR-induced release or translocation of sequestered antigens in the epidermis or dermis; and 3) different specific immunologic effector mechanisms, activated by cytokines and directed against discrete epidermal targets. Several characteristics of photosensitive lupus are discussed in detail: autoantibody specificities, autoantigen translocation, induction of epidermal intercellular adhesion molecule-a (ICAM-1), vascular activation, cytokine release and T-cell activation, and clinical phototesting. The role of antibodies to the extractable nuclear antigens Ro and La and the relationship to subacute cutaneous lupus erythematosus (SCLE) and neonatal lupus erythematosus is discussed in detail, and a model of SCLE is proposed.
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PMID:Pathomechanisms of photosensitive lupus erythematosus. 809 10

Though vasculitic diseases have been claimed to be associated with anti-endothelial cells antibodies (AECA), there is a widespread awareness of the limitations of the tests currently in use. Our objective was therefore to establish clones, in the hope that some of them would express disease-specific membrane autoantigens. Two EC lines and 7 clones were established by fusing human umbilical vein EC with epithelial A549/8 cells, and cloning by limiting dilution. An additional clone was derived from the EA.hy 926 cell line. All clones carried EC markers, such as thrombomoduline (TM) and platelet-EC adhesion molecule 1 but differed from each other, depending on whether they expressed HLA class II antigen, LFA-1, thrombospondin receptor or von Willebrand factor (vWf) antigen. Clones were also characterized by their ability to release tissue plasminogen activator, interleukin 6, TM and vWf. This panel is meant to distinguish reactivities of AECA.
Lupus 1996 Apr
PMID:Establishment and characterization of permanent human endothelial cell clones. 874 22

beta 2-glycoprotein I (beta 2-GP-I) the plasma cofactor for anti-phospholipid antibodies adheres on the endothelial surfaces and can be recognized by anti-beta 2-GP-I antibodies naturally occurring in patients with the anti-phospholipid syndrome. As for the cofactor binding to cardiolipin- or gamma irradiated-plates, the endothelial binding is mediated by the so-called phospholipid binding site, a cationic structure able to react with anionic molecules. Endothelial monolayers appear to represent a substrate able to bind beta 2-GP-I and to present it in a suitable manner in order to allow the binding of anti-beta 2-GP-I beta 2 antibodies. The complex between beta 2-GP-I and the respective antibodies induce an endothelial cell activation as demonstrated by the up-regulation of adhesion molecule expression, the secretion of proinflammatory cytokines and the modulation of arachidonic acid metabolism. Taken together these findings strongly sustain a pivotal role for beta 2-GP-I in allowing antibody deposition on the endothelium and in affecting endothelial cell functions potentially responsible for a procoagulant state.
Lupus 1996 Oct
PMID:Modulation of endothelial cell function by antiphospholipid antibodies. 890 79

The purpose of this paper is to establish whether there is increased lymphocyte adhesion molecule density in systemic lupus erythematosus (SLE), which could alter the migration pathways and activation thresholds of lymphocytes and thus contribute to the pathogenesis of the disease. We analysed the CD11a, CD29 and CD2 bound antibody molecule (bam) density on the CD4+ and CD8+ CAMhigh (primed) lymphocytes of 28 SLE patients (8 active and 20 inactive by BILAG), using reproducible flow cytometric measurements, standardized with fluorescent beads and antibodies of known fluorescein: protein ratios. In a second patient cohort (17 patients), we investigated whether CD29 density on CD8+ cells correlated with measures of humoral (serum IgG) or cellular (urine neopterin) activation. In the first cohort, 36% of patients had elevated CD29 (beta 1 integrin) density on CD8+ cells. In the second cohort, CD29 density on CD8+ cells was found to be closely associated with total plasma IgG (r = 0.71, P = 0.001), but not with urine neopterin, disease activity (BILAG) or drug treatment. We conclude that CD29 on CD8+ cells is associated with B cell activation in SLE.
Lupus 1997
PMID:Correlation between CD29 density on CD8+ lymphocytes and serum IgG in systemic lupus erythematosus. 917 23

One of the characteristic features of the lupus syndrome in humans and mice is the organ-specific accumulation of leukocytes within a variety of different tissues; however, the etiology of this phenomenon remains unclear. The work presented here determined the role of intercellular adhesion molecule (ICAM)-1 in the development of pulmonary leukocyte accumulation by generating MRL/MpJ-Faslpr mice that are genetically deficient in this critical adhesion molecule. Interestingly, these MRL/MpJ-Faslpr ICAM-1 knockout mice exhibit prolonged survival times compared to littermates expressing ICAM-1. We have determined that lack of ICAM-1 completely abrogates the development of pulmonary inflammation but does not prevent the development of autoantibodies, lymphadenopathy, and glomerulonephritis. Furthermore, the lack of pulmonary inflammation was found to be due to decreased migration of leukocytes to the lung rather than decreased in situ proliferation of cells.
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PMID:Intercellular adhesion molecule-1 deficiency prolongs survival and protects against the development of pulmonary inflammation during murine lupus. 927 13


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