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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To further our understanding of autoimmunity, many laboratories have concentrated on the study and manipulation of murine lupus in several strains. Although direct extrapolation of data from animal to man must proceed with caution, the use of such animal systems, both in vitro and in vivo, has been an enormous help in the development of immunologic concepts. Our laboratory has been studying murine lupus by selective breeding of specific genetic immune defects onto New Zealand mice. Specifically, we have used congenital immunologic mutations resulting in asplenia (Dh/+), athymia (nu/nu) and immunodeficiency (Xid) as a means of probing the natural history of immunopathology in one such murine model of autoimmunity New Zealand (NZ) mice. These studies have provided important insights into the ontogeny of autoimmunity. NZB.Xid mice have been particularly valuable and have become a useful tool for dissecting the B cell defects of NZ mice. The Xid gene is dominant over the premature polyclonal activation of NZB mice and acts almost exclusively on B cells that are involved in autoantibody production in NZB mice. Nonetheless, the fact that autoantibody production can occur in a small percent of very old NZB.Xid mice, which have the same phenotype as other NZB.Xid mice, suggests that it can be produced by a mechanism other than a generalized polyclonal expansion and is not dependent on the circulatory or splenic frequency of the Lyb 5 subset of cells. Finally, NZB.Xid mice are unable to produce autoantibodies even after maturing in an aged NZB microenvironment, which suggests that the cell population missing in NZB.Xid mice are important for autoantibody production.
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PMID:The use of congenital immunologic mutants to probe autoimmune disease in New Zealand mice. 295 25

Monoclonal antibodies (MoAb) to L3T4 have been used successfully to suppress autoimmunity in murine models for several human autoimmune diseases. To clarify the immunologic and clinical consequences of treatment with anti-L3T4, we examined the effects of chronic administration of anti-L3T4 on the composition of lymphoid organs, the function of lymphocytes, and the histopathology of autoimmune disease in lupus-prone NZB/NZW F1 (B/W) mice. Weekly treatment with anti-L3T4 (2 mg/mouse) from age 5 to 8 months depleted L3T4+ cells from the spleen and lymph nodes, and prevented the development of splenomegaly and lymphadenopathy. The MoAb bound to target cells in the thymus and modulated their expression of the L3T4 antigen but, in contrast to its effect in extrathymic sites, anti-L3T4 did not deplete the target population from the thymus. In fact, after 3 months of therapy, mice that had been treated with anti-L3T4 had much larger thymuses than control mice that had been treated with saline, suggesting that treatment with anti-L3T4 prevented the thymic atrophy that occurs spontaneously in murine lupus. Despite depleting L3T4+ cells from the spleen, treatment with anti-L3T4 did not diminish the response of splenic lymphocytes to T and B cell mitogens, and it augmented splenic natural killer (NK) cell activity. Finally, treatment with anti-L3T4 decreased the diverse histopathologic manifestations of murine lupus. It dramatically reduced glomerular immunoglobulin and complement deposition and diminished lymphocytic infiltration and vasculitis in the kidneys. Treatment also reduced extrarenal immunopathology, including focal hepatitis and salivary gland infiltration. These observations have implications regarding the use of CD4 MoAb in people with autoimmune diseases.
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PMID:Treatment of murine lupus with monoclonal antibody to L3T4. I. Effects on the distribution and function of lymphocyte subsets and on the histopathology of autoimmune disease. 326 85

Previous studies have demonstrated that the Y chromosome of the BXSB mouse can lead to accelerated autoimmunity in inbred BXSB mice and in F1 hybrids. To additionally study the effects of the BXSB-Y, we have studied three sets of Y-consomic mice, NZB.BXSB-Y, NZW.BXSB-Y, and CBA/J.BXSB-Y, each consisting of background genes from the non-BXSB parent and the Y chromosome from the BXSB mouse. The effect of the BXSB-Y on autoantibody production, immunopathology, and survival was assessed. We found that the CBA/J.BXSB-Y mice showed few differences from control CBA/J males. In contrast, NZW.BXSB-Y males had accelerated renal and cardiac disease and early death, resembling that previously reported for (NZW X BXSB)F1 mice. NZB.BXSB-Y males had accelerated anti-erythrocyte autoantibodies but not accelerated anti-DNA. They lived almost as long as NZB mice. The presence of the BXSB-Y in all of the consomic mice was confirmed by crossing the consomic mice with BXSB females and demonstrating accelerated disease in the male offspring. This study demonstrates that the BXSB-Y chromosome autoimmune accelerating factor does not act alone but operates through other genes, and that the effects on different genetic backgrounds are different. The studies have implications for human lupus; they also provide a basis for future molecular biology studies of the BXSB-Y and the genes upon which it acts.
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PMID:Studies of consomic mice bearing the Y chromosome of the BXSB mouse. 398 99

Mice made neonatally tolerant to alloantigens were found to develop an immunologic disease resembling systemic lupus erythematosus. In BALB/c mice neonatally injected with C57BL/6 X BALB/c F1 hybrid spleen cells, features of autoimmunity were observed first. After 5-24 wk, antinuclear, anti-SS DNA, thymocytotoxic, and rheumatoid factor-like antibodies were detected in association with hypergammaglobulinemia and with the occurrence of circulating immune complexes and cryoglobulins. Some of the antinuclear antibodies were found to be produced by F1 donor B cells persisting in the host. Second, immunopathologic changes were detected in tolerant mice. In the kidneys, an immune complex glomerulonephritis of the membranous type was observed. Immunoglobulin deposits were also found in the choroid plexus and at the dermoepidermal junction. In addition, thrombocytopenia was a common finding, and a positive direct Coomb's test occasionally was detected. Features of autoimmune disease were closely associated with the effective induction of transplantation tolerance, as revealed by the inability of spleen cells to generate in vitro cytolytic responses against C57BL/6 alloantigens. It is suggested that, although transplantation tolerance is associated with a lack of cytolytic reaction of the host against F1 hybrid donor alloantigens, other types of allogeneic interactions could lead in this model to the development of autoimmunity and immunopathology.
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PMID:Autoimmunity and immune complex disease after neonatal induction of transplantation tolerance in mice. 622 73

Two patterns of immune aggregate localization were demonstrated by immunofluorescence and electron microscopy in the choroid plexus of four young women with fatal systemic lupus erythematosus. The two patients with granular immune aggregates localized to the basement membrane of the choroid epithelium (membranous choroidopathy) had subepithelial and intramembranous electron-dense deposits and membranous glomerulopathy in their kidneys. The two patients with immune aggregates in the walls of choroidal blood vessels (vascular choroidopathy) had subendothelial electron-dense deposits and proliferative glomerulonephritis. Vascular deposits in the choroid plexus were associated with capillary thrombi and extravasation of fibrinoid material, while isolated membranous choroidopathy had no histopathologic evidence of inflammation. The clinical presentation and serological studies of blood and cerebrospinal fluid were compared in an effort to discriminate between patients with membranous and vascular choroidopathy. All patients had variable neuropsychiatric symptoms and major motor seizures. While those with vascular choroidopathy had more evidence of disease activity in their sera, both groups demonstrated elevated titers of immune-complexed antinuclear antibodies in cerebrospinal fluid. Although both patterns of choroidal localization of immune aggregates were associated with neuropsychiatric dysfunction, we were unable to identify discrete clinical-symptom complexes which differentiated patients with membranous and vascular choroidopathy. These contrasting patterns of choroid plexus immunopathology suggest that factors responsible for differential localization of immune aggregates are not restricted to the renal glomerulus.
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PMID:Membranous and vascular choroidopathy: two patterns of immune deposits in systemic lupus erythematosus. 664 Oct 23

To investigate further the modulation of autoimmune disease by nutritional means, the influence of zinc deprivation upon the development of the immunopathology of MRL/I mice was studied. Because some effects of zinc deficiency may be due to associated inanition and consequent caloric deprivation, mice with similarly restricted food intake but adequate zinc intake were also studied. Zinc restriction was introduced at either 4 or 10 wk of age and was continued throughout the study. When zinc deficiency was introduced at 4 wk of age, a significant delay in the appearance of the physical findings of MRL/I mice, including open sores, necrotic ears, arthritis, and end-stage cachexia, was noted. In addition, zinc deficiency introduced at this age resulted in a lower incidence and titer of antibodies to dsDNA and less severe glomerulonephritis than control mice. Furthermore, the immune response of zinc-deprived MRL/I mice was better preserved than control animals, and most importantly, survival was significantly prolonged. Pair-fed controls also showed delayed progression of their disease, but animals restricted isocalorically from 4 wk of age experienced a more rapid onset of the lupus-like syndrome than did their zinc-deprived counterparts. In contrast, when zinc deprivation was introduced at 10 wk of age, it had little beneficial effect upon disease progression. Indeed, caloric restriction introduced at this age had a greater impact than did zinc deficiency. Nonetheless, despite the variable influence of zinc deprivation and pair-feeding on autoimmune disease, zinc deprivation, whether introduced at 4 or 10 wk of age, resulted in a significantly greater reduction of lymphoproliferation. Successful modulation of disease activity by nutritional changes will depend on understanding the mechanisms of these differential pathologic processes.
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PMID:Nutritional factors and autoimmunity. III. Zinc deprivation versus restricted food intake in MRL/1 mice--the distinction between interacting dietary influences. 698 39

The role of skin immunopathology in the evaluation and management of patients with systemic lupus erythematosus (SLE) remains controversial. Four simultaneous biopsy specimens from nine patients with SLE (two from buttock and two from forearm skin) were evaluated. Specimens from eight of nine patients showed symmetrical deposits. A poor correlation of skin biopsy score and clinical activity score was noted. A positive correlation was noted between serum C3 levels and skin biopsy score, but a poor correlation was noted with criteria for active nephritis with the exception of microscopic hematuria. In most instances, findings from a single skin biopsy specimen are sufficient and of diagnostic value but correlate poorly with other measurements of disease activity. Serial studies suggested that persistence of cutaneous deposits for many months after flares of SLE may in part explain poor correlation with active disease.
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PMID:Skin immunopathology in system lupus erythematosus. 698 75

The clinically normal skin of the lower back of 30 patients with diabetes mellitus was examined, using the direct immunofluorescence technique. No deposit of immunoglobulins or complement (C3) could be demonstrated, while other authors have previously reported lupus-like deposits in diabetes mellitus. As other discrepant studies of skin immunofluorescence have been published, it is suggested that the standards of the various immunopathology laboratories are different. This may explain why the actual value of the lupus band test remains controversial.
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PMID:An immunofluorescence study of the skin in diabetes mellitus. 701 83

Neurotrophins (NTs), including nerve growth factor (NGF), are multifunctional: in addition to their well-characterized neurotrophic functions they are known to regulate and to be regulated by cytokines, components of the immune system. In line with this we have found expression of a functional trk proto-oncogene, constituting the signal transducing-receptor for NGF, on monocytes/macrophages, lymphocytes and basophils. Moreover, NGF synthesis is regulated by a cytokine cascade including inflammatory mediators such as interleukin-1 and tumor necrosis factor-alpha. The fact that NGF levels are markedly elevated in cerebrospinal fluid of patients with multiple sclerosis and in serum of patients with systemic lupus erythematosus strongly indicates a role for NGF in immunopathology as well as in normal immune function.
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PMID:Neurotrophins and cytokines--intermediaries between the immune and nervous systems. 757 71

Important to the immunopathology associated with the autoimmune disease systemic lupus erythematosus, is the production of autoantibody to DNA. Crucial to understanding the immunological basis for autoimmunity to DNA is knowing whether the anti-DNA autoantibody is the product of clonally-selective, antigen-specific B cell stimulation or non-selective, polyclonal B cell activation. Structural analyses of the immunoglobulin variable-regions of both early, IgM and late, IgG anti-DNA antibodies from lupus-prone (NZB x NZW) F1 mice have indicated that both IgM and IgG anti-DNA autoantibodies are generated by clonally-selective B cell stimulation. Within individual autoimmune mice the later appearing, IgG anti-DNA autoantibodies are structurally similar to the earlier appearing, IgM antibodies, and in some cases both IgM and IgG may be produced by the same B cell clones. The variable-region structural data also suggest that DNA or complexes containing DNA may be the immunogenic stimuli for autoantibody to DNA. In support of this conclusion, normal mice immunized with immunogenic peptide-DNA complexes produce anti-DNA antibodies with structural and serological characteristics similar if not identical to those of autoimmune anti-DNA antibodies. Normal mice immunized with peptide-DNA complexes eventually develop immunopathology that resembles lupus nephritis. These results suggest that autoimmunity to DNA and subsequent autoimmune disease in SLE may result from a specific immune response to DNA containing antigens.
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PMID:Immunoglobulin variable-region structures in immunity and autoimmunity to DNA. 780 11


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