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)

This clinicopathologic study of patients with chronic graft-versus-host disease (GVHD) after allogeneic marrow transplantation emphasizes the most prominent feature of the syndrome, the cutaneous aspects, and describes the ophthalmic-oral sicca syndrome with sialoadenitis and the neurologic findings. Chronic cutaneous GVHD affected 19 of 92 recipients surviving 150 days or more. In 6 patients chronic GVHD presented as a continuation of acute GVHD; in 8 it occurred after the resolution of acute GVHD; and in 5 it arose without preceding acute GVHD, ie, de novo late onset. Two cutaneous types were distinguished. The generalized type affected 16 patients and ran a progressive course resulting in late complications of poikiloderma, diffuse dermal and subcutaneous fibrosis, and contractures. Microscopically, it resembled generalized morphea and lupus erythermatosus hypertrophicus et profundus. The local type affected 3 patients with a more variable picture of poikiloderma, dermal sclerosis, and contractures. Microscopically, it resembled lupus of erythematosus profundus and scleroderma. Guidelines for defining and subclassifying chronic cutaneous GVHD are proposed.
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PMID:Chronic cutaneous graft-versus-host disease in man. 2 21

Two types of lupus mice, NZB/NZW F1 female hybrids and mice with graft-versus-host disease (GVHD), were studied. Histones H3 and H2A were detected by immunofluorescence in glomeruli of 22/22 proteinuric GVHD and 8/12 proteinuric NZB/W F1 female mice; in non-proteinuric animals, 3/5 GVHD and 2/27 NZB/W F1 female were positive. Using antibodies to histone peptides it was shown that mainly the N-terminal regions of histones H3 and H2A were exposed in glomerular deposits. Western blot analysis revealed antibodies to histone subfractions in sera of 33/34 lupus mice that developed proteinuria. This study provides evidence that histones are involved in the pathogenesis of lupus nephritis.
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PMID:Glomerular immune deposits in murine lupus models may contain histones. 145 82

MRL/lpr (lpr) mice spontaneously develop a lupus-like illness as well as massive lymphadenopathy. Attempts to transfer autoimmunity by adoptive transfer or radiation bone marrow chimeras have been unsuccessful. Since severe combined immunodeficiency (SCID) mice have been engrafted with human and rat xenografts without apparent graft-versus-host disease (GVHD), we subjected SCID mice to low-dose irradiation and reconstituted the mice with spleen cells from young or old lpr mice or with lpr bone marrow. Fourteen out of twenty (70%) of SCID mice engrafted with spleen cells from old lpr mice produced autoantibodies (anti-DNA and anti-Sm) without evidence of the severe lymphoid atrophy previously described for lpr spleen-->+/+ chimeras. SCID mice engrafted with spleen cells from young lpr mice developed acute GVHD and 5/6 (83%) died within 4 weeks post-transfer. Although 8/11 (73%) of lpr-->SCID bone marrow allografts survived for at least 4 months, these mice developed a wasting disease characterized by lymphoid atrophy and fibrosis without the production of autoantibodies. None of the lpr-->SCID grafts resulted in the transfer of double negative T cells or the lymphoproliferative syndrome characteristic of MRL/lpr mice. These findings indicate that SCID mice can be engrafted with splenocytes from old MRL/lpr mice and that B cells continue to secrete autoantibodies for several months in the SCID recipients. This study also demonstrates that, unlike i.p. transplant of xenogeneic cells, acute GVHD is a consistent feature of i.p. transplants of normal allogeneic mononuclear cells into SCID mice.
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PMID:MRL/lpr-->severe combined immunodeficiency mouse allografts produce autoantibodies, acute graft-versus-host disease or a wasting syndrome depending on the source of cells. 145 84

The development of glomerulosclerosis was studied in murine chronic graft-versus-host disease (GvHD), which is a model for human systemic lupus erythematosus. The authors investigated the distribution patterns of six components of the extracellular matrix (ECM), i.e., laminin, fibronectin, collagen types I, III, IV, and VI during the course of the disease. All of these ECM components except collagen type I were found in the glomeruli of normal mice, where all of them were intrinsic constituents of the mesangium. Laminin, fibronectin, and collagen type IV were also found in the glomerular capillary walls. Starting 6 weeks after the induction of GvHD and continuing at week 8, the onset of an expansion of the mesangial matrix was observed. At the same time, the amounts of laminin, fibronectin, and collagen types IV and VI increased. Ten weeks after the onset of the disease, glomerulosclerosis developed. Traces of the interstitial collagen type I were found in sclerotic glomeruli. The levels of four ECM components, i.e., collagens III, IV, VI, and laminin were markedly decreased in the sclerotic glomeruli as compared with week 8. In contrast, the amount of fibronectin in the sclerotic glomeruli increased dramatically. Immunoelectron microscopic examination showed fibronectin in the sclerotic lesions, in contrast to laminin, collagen type I, and collagen type IV. It is concluded that the sclerotic lesions in murine chronic GvHD contain fibronectin. The small amounts of the ECM components laminin, as well as collagens III, IV, and VI in the sclerotic glomeruli in GvHD, might represent remnants of mesangial material and collapsed capillary walls. These components are probably replaced by increased production and/or accumulation of collagen type I and fibronectin.
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PMID:A histologic study of the extracellular matrix during the development of glomerulosclerosis in murine chronic graft-versus-host disease. 158 Mar 27

The butterfly rash and malar flush are common facial manifestations of several disorders. Systemic lupus erythematosus may produce a transient rash before any other signs. In pellagra, symmetric keratotic areas on the face are always accompanied by lesions elsewhere on the body. Erysipelas produces brawny, fiery red facial lesions, and scarlet fever causes facial eruptions as part of a generalized eruption. Lupus vulgaris and lupus pernio produce nodules that may spread in a butterfly pattern, and seborrheic dermatitis has a predilection for the malar prominences and other areas of the face. Carcinoid syndrome often causes flushing attacks that vary in duration, and facial flushing that lasts throughout treatment may accompany chemotherapy if the patient has a hypersensitivity reaction. Deep-red rashes and/or lichenoid lesions may be caused by graft-versus-host disease in a patient undergoing bone marrow transplantation.
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PMID:The butterfly rash and the malar flush. What diseases do these signs reflect? 183 28

We have attempted herein to demonstrate how microbial superantigens could promote an abnormal form of "cognate" T helper-B cell interaction, analogous to that which may occur during GVH disease, leading to B cell activation and systemic autoimmunity. In vitro studies performed at our laboratory and others have demonstrated that resting human B cells bind microbial superantigens and present them to superantigen-reactive autologous T helper cells, resulting in T cell activation and polyclonal IgM and IgG production by the superantigen-bearing B cells. In vitro studies of microbial superantigen-mediated murine T helper-B cell interactions demonstrate preferential help for B cells that have encountered specific antigen. Both in humans and in mice, the cellular interactions involved and the B cell responses induced are highly analogous to those mediated by allospecific T helper-B cell interaction. Finally, the results of studies carried out on T cell-deficient (nude) mice suggest that microbial superantigens may trigger similar T helper cell-dependent polyclonal IgM and IgG responses in vivo. These mice will be studied over time and tested for the development of autoantibodies characteristic of SLE and of autoimmune organ system damage, the occurrence of which are predicted by our model.
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PMID:A potential role for microbial superantigens in the pathogenesis of systemic autoimmune disease. 182 27

Induction of a graft-versus-host (GVH) reaction (GVHR) in non-irradiated (C57BL/10ScSn x DBA/2)F1 mice (BDF1) with DBA/2 lymphoid cells leads to chronic GVH disease (GVHD). One of the pathological alterations of this type of GVHD is hyperplasia of host B cells with production of lupus-like autoantibodies. This hyperstimulation of host B cells has previously been demonstrated to be induced by alloreactive donor T helper cells that were also proposed to maintain it. We provide three pieces of experimental evidence in support of this concept. First, treatment of mice with chronic GVHD by injection of monoclonal anti-Thy-1.2 antibodies, performed at week 6 after the injection of C57BL/6 lymphoid cells into (C57BL/6 x C57BL.bm12)F1 mice led to a significant decrease in the titre of anti-nuclear antibodies. Second, CD4+ donor T cells persisted in BDF1 mice with GVHD (GVHF1) for at least 10 weeks after the induction of GVHR; these T cells showed alloreactive helper activity against H-2b MHC determinants of the opposite parent in vitro. Third, T cells of GVHF1 mice, obtained 2 months after the induction of GVHR and transferred into normal secondary recipients, induced signs of chronic GVHD in DBF1 but not in DBA/2 mice. The combined results show that persisting donor T helper cells in GVHF1 mice retain their alloreactivity towards H-2 class II antigens for a long time after the induction of GVHR and they strongly suggest that these T cells are also the driving force behind the production of lupus-like autoantibodies at the late stage of chronic GVHD.
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PMID:Persistence of allospecific helper T cells is required for maintaining autoantibody formation in lupus-like graft-versus-host disease. 214 86

In spite of intensive endeavours, attempts to identify nephritogenic antigens in cases of immune complex glomerulonephritis have not yielded convincing results. Cationic antigens can have high affinity for the glomerular basement membrane and are prime candidates as nephritogens. They can be expected to play a role in post-infectious and in autoimmune glomerular disease. Histones show great promise in the latter case: we are able to demonstrate (1) a high affinity for the glomerular basement membrane and (2) their ability to promote glomerular deposition of anionic antigens as an additional target. Histones were detectable in glomerular deposits in two murine models of glomerulonephritis: the spontaneous lupus-like disease of NZB/W F1 mice and in graft-versus-host disease. We propose that histones may be responsible for the induction of glomerulonephritis in lupus-like syndromes, as well as other types of autoimmune renal disease. As an analogue, histone-like proteins from micro-organisms may also be responsible for glomerular disease in post-infectious nephritis.
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PMID:The role of cationic proteins in the pathogenesis of immune complex glomerulonephritis. 215 42

A chronic GVH reaction induced in normal mice results in a syndrome that closely resembles SLE. In this study, we compared the autoimmune GVH syndrome induced in parent (C57BL/6Kh [B6] and B6.C-H-2bm12 [bm12]) and F1 [( B6 x bm12]F1) mice by transfer of parental spleen cells. A majority of the mice in all groups developed autoantibodies to chromatin and erythrocytes, and some of the mice also produced anti-dsDNA antibodies. The predominant isotype of the anti-chromatin autoantibodies was found to be IgG2a, although high levels of IgG2b antibodies were also present. Autoantibody production was in general more intense and more prevalent in parent----F1 hybrid combinations, compared to parent----parent infusions. No influence of host or graft gender was observed. These studies show that a chronic GVH reaction can be induced by both parent----parent and parent----hybrid combinations.
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PMID:Experimental induction of systemic lupus erythematosus by recognition of foreign Ia. 220 7

The pathogenesis of renal involvement was studied in murine chronic graft-versus-host disease (GVHD), which is a model for human systemic lupus erythematosus. GVHD was induced by four i.v. injections of lymphocytes from DBA/2 donor mice into (C57BL/10 x DBA/2)F1 hybrids at 3-4-day intervals. Two weeks after the first injection, antibodies were found to have been deposited in the mesangium and along the glomerular basement membrane (GBM) in a linear arrangement, which changed to a granular pattern after 6-8 weeks. In this stage, large electron-dense complexes were present both subepithelially and subendothelially along the GBM. Proteinuria increased up to 11,300 +/- 2140 micrograms/18 h. Indirect immunofluorescence studies and ELISA showed that sera and kidney eluates contained autoantibodies directed against nuclear antigens and GBM component laminin as well as against renal tubular epithelial antigens (RTE). The specificity of the anti-RTE antibodies was further characterized by the use of absorption techniques as well as immunoblotting. The early linear immunofluorescence pattern seems to be associated with glomerular binding of anti-GBM antibodies, while electron-dense complex formation in later stages may be induced by the superimposed deposition of anti-RTE antibodies. Similar phenomena were recently described in Heymann's nephritis in the rat, a model for human membranous nephropathy.
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PMID:Pathogenesis of experimental lupus nephritis: a role for anti-basement membrane and anti-tubular brush border antibodies in murine chronic graft-versus-host disease. 230 29


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