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)

Pathological skin reactions were induced with both UVA and UVB in 12 patients with lupus erythematosus (LE) and with UVA in 7 with polymorphous light eruption (PMLE) but in none of the controls. Biopsy specimens taken from UV-induced lesions showed that in dermal infiltrates of LE cases CD4-positive cells predominated, whereas in the majority of PMLE cases CD8-positive cells predominated. Keratinocytes expressed intercellular adhesion molecule-1 (ICAM-1) in 7 of the 12 UVA- and in eight of the ten UVB-induced LE lesions, and in three of the UVA-induced lesions of PMLE patients. Three different staining patterns were found. In subacute cutaneous LE (SCLE) cases staining throughout the epidermis resembled that seen in genuine SCLE lesions. In discoid LE (DLE) lesions, the staining was most prominent in and near the basal cell layer. In the one systemic LE case and in the PMLE cases, ICAM-1 expression was seen only in association with epidermal spongiosis and T-cell infiltration. Keratinocytes did not express ICAM-1 in the controls or in the non-irradiated skin of the LE patients. In five on the UVA-induced lesions, in eight of the UVB-induced LE lesions and in one of the PMLE cases, keratinocytes expressed CD36. In four of the six LE lesions with fewer CD1a-positive cells, dendritic CD36-positive cells were seen in the epidermis. In conclusion, the pattern of activated keratinocytes and immunocompetent cells in the dermis was similar to that seen in genuine LE and PMLE lesions, but dissimilar to each other and to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of intercellular adhesion molecule-1 (ICAM-1) and OKM5 in UVA- and UVB-induced lesions in patients with lupus erythematosus and polymorphous light eruption. 769 27

Bromocriptine (BRC) is a dopamine agonist that suppresses the secretion of prolactin by the pituitary gland and is known to have immunomodulating properties. In the present study, we investigated the effect of BRC on the development of two autoimmune experimental models: (i) systemic lupus erythematosus (SLE), induced by injection of a human anti-dsDNA monoclonal antibody (MIV-7); (ii) primary anti-phospholipid syndrome (PAPS), induced by injection of a mouse anticardiolipin monoclonal antibody (CAM). BRC had a suppressive effect on in vivo autoantibody production, as well as on the appearance of other manifestations of the respective disease. The BRC activity seems to be nonspecific, since the same effect was demonstrated in mice with lupus and with PAPS. These data were supported by the in vitro nonspecific effect of CD8 cells induced in vivo by bromocriptine, on specific lymph node cell proliferation in the presence of the pathogenic monoclonal antibodies (MIV-7 or CAM, respectively), and on the response to an irrelevant autoantigen, myelin basic protein. These data were complemented by the nonspecific suppressive effect by the T-suppressor factor, produced by the CD8 cells, on specific thymidine uptake by lymph node cells from experimental SLE or PAPS in the presence of the immunizing mAb. Injection of CD8 cells from BRC-treated mice with SLE or PAPS abolished the disease development in the lupus and PAPS experimental models. The data suggest a possible novel role of bromocriptine in downregulating autoimmune phenomena through induction of natural nonspecific CD8+ suppressor cells.
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PMID:Bromocriptine immunomodulation of experimental SLE and primary antiphospholipid syndrome via induction of nonspecific T suppressor cells. 770 99

We have determined the effect of anti-CD4 or anti-CD8 monoclonal antibody (mAb) treatment from birth on the generation of the lpr CD4- CD8- double-negative (DN) T cell subset and on the development of lupus-like autoimmune syndrome in MRL-lpr/lpr mice. Both anti-CD4 and anti-CD8 mAb treatments resulted in a marked inhibition of lymph-adenopathy, whereas the development of the lpr DN T cells and of the lupus-like autoimmune syndrome strikingly differed in these two groups of mice. The treatment with anti-CD8 mAb almost completely blocked the appearance of the lpr DN T cells without any significant effect on the development of lupus-like autoimmune syndrome in MRL-lpr/lpr mice. In contrast, mice treated with anti-CD4 mAb failed to develop a lupus-like syndrome, while they still developed the lpr DN T cell subset, the predominant population in their lymph nodes, although absolute numbers were markedly diminished. Our results support the idea that CD8+ T cells are a major source of the lpr DN T cells, and that the lpr DN T cells play a minor, if any, role in the pathogenesis of lupus-like autoimmune syndrome in MRL-lpr/lpr mice.
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PMID:Effect of long-term anti-CD4 or anti-CD8 treatment on the development of lpr CD4- CD8- double negative T cells and of the autoimmune syndrome in MRL-lpr/lpr mice. 773 35

We investigated a possible association between markers of immune activation and disease activity in 52 patients with systemic lupus erythematosus (SLE). Serum concentrations of neopterin, beta-2-microglobulin, 55 kD-type soluble tumor necrosis factor receptor, soluble interleukin-2 receptor and soluble CD8 were compared to the Index of European Consensus Lupus Activity Measurement (ECLAM). All markers of immune activation, except sCD8, significantly correlated with ECLAM. Stepwise multiple linear regression analysis revealed erythrocyte sedimentation rate and neopterin to correlate best with ECLAM (multiple correlation coefficient = 0.74, P < 0.001). The study shows that serum neopterin concentrations are a useful independent index for disease activity in SLE. The finding of enhanced concentrations of various parameters of immune activation in patients confirm a role of the T cell and macrophage activation in the pathogenesis of SLE.
Lupus 1995 Feb
PMID:Serum soluble markers of immune activation and disease activity in systemic lupus erythematosus. 776 35

We conducted a clinicopathologic study of 79 cases of Kikuchi's disease. Our results confirmed that Kikuchi's disease is a distinctive type of necrotizing lymphadenitis that affects primarily the cervical lymph nodes of young adults and has a self-limited clinical course. However, female predominance was not as striking as heretofore reported. A low, but possible, recurrence rate of 3.3% was documented. Extranodal cutaneous involvement occurred in one patient who had a more severe and protracted clinical course. Classification of the histopathologic changes into three histologic types was proposed: proliferative, necrotizing, and xanthomatous types. These three types differed in certain aspects of their clinical features. Immunohistologic analysis revealed that the predominant cells of the lesions were various types of histiocytes, including the enigmatic plasmacytoid monocytes. A variable number of CD8(+) T cells correlating with the duration of the disease was detected. B cells were nearly absent, and only an insignificant number of OPD4(+) T cells was present. Eight cases studied by the flow cytometric DNA analysis all showed a diploid DNA content. Although the histologic changes of Kikuchi's disease were variable, the findings were sufficiently distinctive to permit accurate diagnosis. Malignant lymphoma and especially lupus lymphadenitis can be mistaken for Kikuchi's disease; thus differentiation is crucial.
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PMID:Kikuchi's disease (histiocytic necrotizing lymphadenitis). A clinicopathologic study of 79 cases with an analysis of histologic subtypes, immunohistology, and DNA ploidy. 779 78

To evaluate the role of V beta 8+ T cells in the development of lupus-like autoimmune syndrome in MRL-lpr/lpr mice, we treated them with the F23.1 anti-V beta 8 monoclonal antibody (mAb) from birth to 4 months of age. Here we report that almost complete depletion of V beta 8+ T cells by the F23.1 mAb treatment neither inhibited nor delayed the development of hypergammaglobulinemia, autoantibody production and autoimmune glomerulonephritis in MRL-lpr/lpr mice. In addition, the F23.1 mAb treatment did not prevent the development of lymphadenopathy and the generation of a CD4-CD8- double-negative T cell subset, characteristically accumulating in lpr lymph nodes. Our results strongly argue against the idea that the V beta 8+ T cells play a critical role in the development of lupus-like autoimmune syndrome in MRL-lpr/lpr mice.
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PMID:Lack of association of V beta 8+ T cells with lupus-like syndrome in MRL-lpr/lpr mice. 802 33

In this study, we investigated UVB-light-induced cytotoxicity and the binding of antibodies to extractable nuclear antigens on cultured keratinocytes from patients with cutaneous lupus erythematosus (LE). Keratinocytes from cutaneous LE patients showed a higher susceptibility to single-dose UVB light irradiation compared to keratinocytes from normal controls. The binding of antibodies to U1RNP and Ro/SS-A antigens on cultured keratinocytes was induced by UVB light and more up-regulated when cultured keratinocytes were reacted with autologous sera. Antibody-dependent cellular cytotoxicity (ADCC) was induced when cultured keratinocytes irradiated with UVB light were combined with autologous sera, using peripheral mononuclear cells of normal controls. Immunohistochemical studies of skin biopsy specimens from patients with systemic LE revealed an increased number of epidermal Langerhans cells at the peripheral sites of skin lesions and a relative dominance of infiltrative CD8-positive lymphocytes in the central area of skin lesions. Based on these findings we suggested that ADCC mechanisms were involved in the development of skin lesions, and the distribution of Langerhans cells and infiltrated CD8 cells were responsible for the expansion and persistence of lesions.
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PMID:Susceptibility to UVB light in cultured keratinocytes of cutaneous lupus erythematosus. 804 57

The autosomal recessive mutant gene, lpr, has been shown to accelerate the progression of lupus-like autoimmune disease, which is associated with a massive expansion of a unique CD4-CD8- double-negative T cell subset, in MRL/MpJ mice. Here we report a substrain of MRL/MpJ-lpr/lpr (MRL-lpr) mice which live almost twice as long with delayed development of glomerulonephritis, compared with conventional MRL-lpr mice. This substrain, termed MRL-lpr.II (II for long-lived), develops generalized lymphadenopathy characteristically seen in MRL-lpr mice. However, the expansion of a double negative lpr T cell subset is markedly limited with a mean value of 15% in their lymph nodes compared to about 70% in conventional MRL-lpr mice. Overall production of autoantibodies, such as anti-DNA and rheumatoid factors, does not significantly differ between the two MRL-lpr mice. However, serum levels of cryoglobulins, whose major component is IgG3, are markedly diminished in MRL-lpr.II mice with a parallel decrease in IgG3. Since MRL-lpr.II mice still carry the lpr mutation, as documented by the presence of defects in the Fas antigen, a possible new mutation in this substrain may play a significant role in the pathogenesis of lupus-like autoimmune syndrome.
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PMID:An MRL/MpJ-lpr/lpr substrain with a limited expansion of lpr double-negative T cells and a reduced autoimmune syndrome. 831 55

We have studied the ability of the lupus prone MRL lpr/lpr (MRL/lpr) and (NZBxNZW)F1 (NZB/W) female mice to raise granulocyte mediated inflammatory responses. These autoimmune strains, known to exhibit severe anergy as concerns T cell dependent immune function, are not well analysed with respect to neutrophil-mediated inflammatory responses. An in vivo model of granulocyte mediated inflammation has been developed in our laboratory. A single intradermal injection of olive oil into mouse footpad induces massive infiltration of polymorphonuclear cells (PMNC) within 24 h. This extravasation of PMNC gives rise to a localized footpad swelling, which can be easily and reproducibly measured and relates to severity of the inflammatory process. T cell independence of this inflammatory model was ascertained by in vivo T cell depletion using monoclonal antibodies to CD4 and CD8 molecules. Olive oil triggered inflammation was inducible in both young and aged lupus mice. The intensity of footpad swelling upon olive oil injection was similar in lupus mice and in healthy control strains. In contrast, aged MRL/lpr and NZB/W mice showed severely depressed T cell dependent inflammatory responses as assessed by delayed type hypersensitivity reaction to sheep red blood cells. We conclude that the PMNC mediated inflammatory potential is not affected in severely diseased lupus mice. The increased numbers of circulating PMNC together with intact PMNC function may explain why severely immune deficient lupus mice seldom show clinical signs of bacterial infection.
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PMID:Neutrophil mediated inflammatory response in murine lupus. 832 62

To further understand the contribution of I-A to the development of disease in murine lupus, we compared the incidence and/or titers of natural thymocytotoxic autoantibodies (NTAs), autoantibodies to red blood cells, gp70 immune complexes (gp70), antibodies to Sm, and rheumatoid factor in NZB (H-2d), NZB.H-2b and NZB.H-2bm12 mice. There were striking and significant differences among the three NZB strains in several of these parameters. NZB (H-2d) and NZB.H-2bm12 mice had a 100% incidence of NTA. In contrast, NZB.H-2b mice were found to have NTA in only 36% of animals at 8-10 months of age. Furthermore, the NTA titers of NZB.H-2bm12 mice were relatively low. There were also distinct differences between these strains with respect to the presence of antibodies to anti-erythrocytes (positive Coombs' test). NZB (H-2d) and NZB.H-2bm12 both had high titers of anti-erythrocyte autoantibodies (AEAs), whereas there was a delayed onset and lower titers in NZB.H-2b mice. Additionally, there was a dramatic increase in gp70 IC levels in NZB.H-2bm12 mice. In previous studies, NZB.H-2bm12 as well as NZB.H-2bm12 x NZB.H-2b F1 mice were found to produce high autoantibody titers to single-stranded (ss) and double-stranded (ds) DNA. Using unfractionated or fractionated splenic T cells (CD4+ CD8-, CD4- CD8+, or CD4-CD8-) from NZB.H-2b or NZB.H-2bm12 mice, we compared their relative abilities to cooperate with T-depleted splenocytes from NZB.H-2bm12 x NZB.H-2b F1 mice to produce antibodies to ss- and ds-DNA. Only T cells, including both CD4+ CD8- and CD4- CD8- populations, from NZB.H-2bm12 mice, were able to induce such autoantibody production among F1 splenocytes. Finally, marked alterations in splenic T cell subsets were found in NZB.H-2bm12 mice compared to NZB.H-2b mice, and to a lesser extent, in B6.C-H-2bm12 mice compared to C57BL/6 (H-2b) mice. These data further highlight the influence of I-A on autoimmunity and in particular the influence of the bm12 mutation on altering the natural history of disease expression in NZB mice.
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PMID:The contribution of I-Abm12 to phenotypic and functional alterations among T-cell subsets in NZB mice. 838 89


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