Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Functions of B cells from (NZW x BXSB)F1 (W/BF1) mice are investigated. The W/BF1 mouse, which is an animal model for systemic lupus erythematosus (SLE) and immune thrombocytopenic purpura (ITP), produces anti-DNA and anti-platelet antibodies; W/BF1 mice show hypergammaglobulinemia (particularly increases in IgG2a and IgG2b). The ratio of small resting B cells to large activated B cells in W/BF1 mice is low compared to normal mice, suggesting that B cells in W/BF1 mice are already activated in vivo. Furthermore, small resting B cells separated by a Percoll density gradient technique show hyper-responsiveness to lipopolysaccharide (LPS) or anti-mu plus IL-4. This suggests that B cells in W/BF1 mice are genetically programmed to be easily activated, resulting in the overproduction of autoantibodies. A significant number of CD5+ B cells are found in the lymph nodes of old W/BF1 mice. These findings indicate that all cells in the B cell lineage of W/BF1 mice are already activated in vivo.
 ...
PMID:Functional analyses of B cells in (NZW x BXSB) F1 mice. 769 97

Gastrointestinal vasculitis is a fatal aspect of systemic lupus erythematosus. Whether lupus-prone strains of mice develop gastrointestinal vasculitis, and whether it is accompanied by elevated titres of anticardiolipin autoantibody is not known. Lupus-prone (NZW X BXSB)F1 (W/BF1) mice, and other strains were examined immunohistologically. Levels of anticardiolipin autoantibody and circulating immune complexes were determined by microELISA. Reciprocal haploidentical marrow transplantations between W/BF1 and autoimmune-resistent B6C3F1 mice were made. Young adult W/BF1 mice had the highest incidence of gastrointestinal vasculitis (61%), and the highest mean titre of anticardiolipin autoantibody. Lesions consisted of subintimal fibrinoid degeneration in arterioles of the duodenum, jejunum and ileum, and were prevented, or alternatively induced by reciprocal marrow transplantations between W/BF1 and B6C3F1 mice. Mice engrafted with W/BF1 marrow which developed vasculitis had higher titres of anticardiolipin autoantibodies than engrafted mice free of vasculitis (P < 0.005). This represents the first report of gastrointestinal vasculitis as an aspect of systemic autoimmunity in lupus-prone mice. The concurrent elevation of anticardiolipin autoantibody and development of vasculitis suggests that anticardiolipin autoantibodies, and their proposed thrombogenic and vascular injury consequences, contribute to development of microvasculitis in lupus-prone mice.
 ...
PMID:Gastrointestinal vasculitis in autoimmune-prone (NZW X BXSB)F1 mice: association with anticardiolipin autoantibodies. 777 89

The (NZW x BXSB)F1 (W/BF1) mouse is known to be an animal model of systemic lupus erythematosus (SLE) and immune thrombocytopenic purpura (ITP). These mice produce not only anti-DNA antibodies but also anti-platelet antibodies, resulting in decreased platelet counts. They show a high level of proteinuria, increased white blood cell (WBC) counts, hypertension, and myocardial infarction due to the high levels of anti-cardiolipin antibodies. When W/BF1 mice (4-5 months) were lethally irradiated and then reconstituted with T cell-depleted bone marrow cells of normal BALB/c mice (8 weeks), 60% of the mice survived more than one year. The WBC and platelet counts in the mice were normalized, and the levels of anti-DNA and anti-platelet antibodies decreased. The renal dysfunction was also ameliorated as indicated by a lower level of proteinuria, lower levels of serum creatinine (S-CRTN) and blood urea nitrogen (BUN), and by improved histology. The blood pressure (BP) of the treated W/BF1 mice decreased due to the improved renal functions. In contrast to the non-treated W/BF1 mice which died of myocardial infarction or renal failure by the age of 7 months, the treated W/BF1 mice showed no evidence of myocardial infarction even one year after BMT. This was due to the lower cardiolipin levels.
 ...
PMID:Effect of bone marrow transplantation on antiphospholipid antibody syndrome in murine lupus mice. 778 96

Male (NZW x BXSB)F1 (W/BF1) mice develop systemic autoimmunity involving autoantibodies, thrombocytopenia, lupus nephritis, and coronary vascular disease (CVD) with myocardial infarction. To determine whether this murine lupus-associated CVD can be prevented by the reduction of dietary calories, male W/BF1 mice were separated into five experimental groups and fed either ad libitum (designated group A, n = 50), fed 32% fewer calories of an otherwise comparable diet (designated group B6, n = 20), or initially fed ad libitum and then switched to reduced calorie intake (RCI) feeding at ages 14, 17, or 22 weeks (designated B14, n = 10; B17, n = 20; or B22, n = 20). Occlusive CVD was prevented by RCI. Life-span was significantly extended among the early onset RCI cohorts, B6 and B14 (P = 0.0001 and P = 0.005), compared to group A mice. Mean anti-cardiolipin autoantibody titers and mean levels of circulating immune complexes were also lowered in RCI mice when all RCI mice were compared to ad libitum fed group A mice. Histological grades of both coronary vascular and glomerular lesions were significantly less than those of group A mice (P < 0.001). Immunoprecipitates indicative of immunoglobulin deposition within coronary or glomerular vascular walls were also substantially less than those of group A mice. These findings indicate a possible causal role for anti-cardiolipin autoantibody in development of autoimmune CVD in W/BF1 mice and suggest that regulating dietary calories can influence the mechanism involved in pathogenesis of autoimmune-associated CVD development.
 ...
PMID:Calorie restriction prevents the occlusive coronary vascular disease of autoimmune (NZW x BXSB)F1 mice. 818 20

Male (NZW x BXSB)F1 (W/BF1) mice develop systemic autoimmunity involving autoantibodies, thrombocytopenia, lupus nephritis, and coronary vascular disease with myocardial infarction (CVD). To determine whether this murine lupus-associated CVD could be transferred to otherwise autoimmune-resistant (C57BL/6 x C3H/He)F1 (B6C3F1) mice via W/BF1 T-cell-depleted marrow (TCDM) transplants, or conversely whether the CVD of W/BF1 mice could be prevented by the reciprocal transplant, reciprocal haploidentical transplants of TCDM were performed. CVD developed only in mice with systemic autoimmunity. Mice that developed lupus had glomerulonephritis and thrombocytopenia and also had elevated titres of autoantibodies to double-strand DNA, cardiolipin, and platelets and elevated levels of circulating immune complexes. Of control W/BF1 mice, 80% developed lupus, and of these, 81% developed CVD with a mean grade of 2.5 +/- 0.8. Engraftment of W/BF1 mice with B6C3F1 marrow protected 90% of the recipients from the development of lupus, and none developed CVD. Engraftment of B6C3F1 mice with W/BF1 marrow induced lupus in 60% of the recipients, and of those, 33% developed CVD with a mean grade of 1.3 +/- 0.3. The B6C3F1 recipients of W/BF1 marrow which developed CVD had significantly higher titres of autoantibodies to cardiolipin (aCL; P < .01). These findings show that genetic abnormalities present in the W/BF1 hematopoietic stem cells contribute to autoantibody development, including aCL, and suggest that thrombogenic mechanisms induced by aCL may contribute to the development of CVD in this form of murine lupus erythematosus.
 ...
PMID:Prevention and induction of occlusive coronary vascular disease in autoimmune (W/B)F1 mice by haploidentical bone marrow transplantation: possible role for anticardiolipin autoantibodies. 821

Male (NZW x BXSB)F1 (W/BF1) mice develop a systemic lupus-like syndrome characterized by thrombocytopenia, coronary vascular disease, nephritis, and anticardiolipin antibodies. Three stable hybridoma cell lines secreting monoclonal anticardiolipin antibodies were developed from these mice by fusing their splenic lymphocytes with nonsecreting myeloma cell line, NS-1. Monoclonal antibody A1.17 reacted with cardiolipin in a beta2-Glycoprotein I-dependent manner. The epitope for this antibody consisted of beta2-glycoprotein I bound to cardiolipin or immobilized on plastic plates. Other anionic phospholipid-binding proteins, such as prothrombin or annexin V, had no significant effect in the reactivity of these antibodies. The specificity is similar to the autoimmune anticardiolipin antibodies described in patients with systemic lupus erythematosus and other infectious diseases. In contrast, monoclonal antibodies A1.72 and A1.84 reacted with cardiolipin in the absence of beta2-glycoprotein I. Beta2-glycoprotein I, either in the fluid phase or bound to cardiolipin, inhibited the binding of these antibodies. The specificity of the latter two antibodies was similar to that described in patients with syphilis and allied disorders. Both types of antibodies had lupus anticoagulant properties. Thus lupus-prone male (NZW x BXSB)F1 (W/BF1) mice develop both beta2-glycoprotein I-dependent and beta2-glycoprotein I-independent anticardiolipin antibodies.
 ...
PMID:Characterization of beta2-glycoprotein I-dependent and -independent "antiphospholipid" antibodies from lupus-prone NZW/BXSB F1 hybrid male mice. 932 49