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)

In the present study, an analysis was made of the expression pattern of thrombospondin-1 (TSP1) and its receptor (CD36) in skin biopsies obtained from healthy volunteers and from patients with lichen planus, lupus erythematosus, cutaneous T-cell lymphoma and psoriasis vulgaris. Using monoclonal antibodies against TSP1 in biopsies from the healthy volunteers and from both clinically involved and uninvolved skin of the patients, a specific peroxidase-positive reaction was detected around the sweat glands in the dermis. In all cases investigated, the CD36-positive lesional keratinocytes remained TSP1-negative. These findings favour the hypothesis that CD36-positive keratinocytes might have some functional relevance via oxidized low-density lipoprotein and/or collagen fibrils, without any connection with TSP1.
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PMID:Expression of thrombospondin-1 (TSP1) and its receptor (CD36) in healthy and diseased human skin. 752 82

Thrombospondin is a multifunctional 450 kD glycoprotein which may be secreted into the extracellular matrix by a wide variety of cells. Occasional foci of immunoreactive thrombospondin have previously been demonstrated within normal human glomeruli. A specific polyclonal antibody directed against thrombospondin 1 was used to examine the distribution of this regulatory glycoprotein in renal biopsies from patients with a variety of renal diseases, including rapidly progressive glomerulonephritis associated with circulating antibodies to neutrophils, active or quiescent systemic lupus erythematosus, and membranous nephropathy, together with normal renal tissue. The results demonstrated the marked up-regulation of thrombospondin expression in acutely inflamed renal tissue with strongly positive, predominantly extracellular staining of glomerular crescents, although cytoplasmic staining of epithelial cells was also seen, indicating that these cells may contribute to thrombospondin accumulation at these sites. Occasional segmental mesangial staining was seen in cases of active lupus and rapidly progressive glomerulonephritis, while some focal interstitial staining around peritubular capillaries was seen in all renal tissue examined. These results suggest that thrombospondin may play an important role in the regulation of cellular recruitment, proliferation, and function in crescentic glomerulonephritis.
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PMID:Expression of the multifunctional extracellular matrix protein thrombospondin in crescentic glomerulonephritis. 877 23

Interstitial cells, inflammatory-immune cells, tubular cells and endothelial cells of the peritubular capillaries have arisen as possible major players of the nephron damage in lupus nephritis. Increased ICAM-1, Von Willebrand factor, soluble endothelial protein C receptors and decreased ADAMS-13 point to a diffuse vascular damage. Albuminuria elicits a rapid generation of hydrogen peroxide in proximal tubular cells along with nuclear factor-kB activation, endothelin-1 and transforming growth factor (TGF-beta1) upregulation. TGF-beta1 enhances epithelial-to-mesenchymal transdifferentiation. Albuminuria also enhances the expression of macrophage chemotactic protein-1 and macrophage inflammatory protein-1alpha, thus leading to increased interstitial inflammation. TGF-beta1 and thrombospondin-1, a putative activator of TGF-beta, induce apoptosis of peritubular capillaries, as well as of glomerular endothelial cells. All these events can be counteracted by hepatocyte growth factor (HGF), which is expressed by the epithelial tubular cells and stimulates the growth of epithelial cells (mitogen), enhances the motility of epithelial cells (motogen), induces renal epithelial tubule regeneration (morphogen) and enhances angiogenesis (angiogen). The balance between TGF-beta1 and HGF could be a key to define the prognostic value of kidney histopathology at baseline and during follow-up, in lupus nephritis. Therapeutic strategies aiming at altering the biological balance in the patients are at hand to test and prove the experimental evidences.
Lupus 2008 Jun
PMID:Renal interstitial cells, proteinuria and progression of lupus nephritis: new frontiers for old factors. 1853 6

We analyzed 66 cases of immune-mediated thrombophilia in patients with lymphoma reported in the literature. Sixty-one cases had a lupus anticoagulant, three an antibody to protein S, one to protein C, and one to ADAMTS 13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Lupus anticoagulants occurred in all histological subtypes of non-Hodgkin lymphoma, except mantle cell lymphoma, MALT (mucosa-associated lymphoid tissue) lymphoma, and angioimmunoblastic T-cell lymphoma, and rarely in Hodgkin lymphoma. The largest number of cases was described in splenic marginal zone and lymphoplasmacytic lymphoma. Lupus anticoagulants were highly associated with immunoglobulin M (IgM) paraproteinemia, autoimmune hemolytic anemia, and immune thrombocytopenia. About half of the patients had thrombotic events (antiphospholipid antibody syndrome). Venous thromboembolism was more than twice as common as arterial thrombosis; 6.5% had a catastrophic antiphospholipid antibody syndrome. The lupus anticoagulant could be eliminated by lymphoma treatment (chemoimmunotherapy or splenectomy) in more than one-third of patients. It is suggested that a search for lupus anticoagulant should be done in all patients with lymphoma, because a diagnosis of lupus anticoagulant may influence the management of lymphomas in some patients.
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PMID:Acquired immune-mediated thrombophilia in lymphoproliferative disorders. 2176 5

Membranous nephropathy (MN) associated with malignancies is a well-known entity. However, its association with benign neoplasm is not broadly recognized. A 69-year-old man with recurrent nephrotic syndrome presented with pedal edema and proteinuria of 5 months' duration. Laboratory results showed hypoalbuminemia and hyperlipidemia. Proteinuria was estimated to be protein excretion of 3.5g/d. Studies were negative for viral hepatitis, syphilis, human immunodeficiency virus, autoimmune diseases, and paraproteinemia. Kidney biopsy disclosed MN with negative phospholipase A2 receptor (PLA2R) staining, favoring a secondary form of MN. Computed tomography detected a 7.6-cm duodenal schwannoma. Elective surgical resection was performed. Pathologic study showed that THSD7A (thrombospondin type 1 domain-containing 7A) was positive in both glomeruli and schwannoma. Commonly, secondary MN is related to underlying conditions, including lupus, hepatitis, and neoplasm, and can be medication induced. The risk for developing a concomitant neoplasm among patients with PLA2R-negative MN is up to 12 times higher than in the general population. Most of these neoplasms are malignancies, and the presence of autoantibodies directed at similar tissue targets is hypothesized as the potential mechanism. In our case, THSD7A may be the autoantibody that has linked the schwannoma and the development of MN. Although benign tumors rarely produce renal manifestations, effective treatment may lead to resolution of nephrotic syndrome.
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PMID:Duodenal Schwannoma as a Rare Association With Membranous Nephropathy: A Case Report. 3045 84

Membranous nephropathy (MN) is an immune complex-mediated cause of the nephrotic syndrome that can occur in all age groups, from infants to the very elderly. However, nephrotic syndrome in children is more frequently caused by conditions such as minimal change disease or focal segmental glomerulosclerosis, and much less commonly by MN. While systemic conditions such as lupus or infections such as hepatitis B may more commonly be associated as secondary causes with MN in the younger population, primary or "idiopathic" MN has generally been considered a disease of adults. Autoantibodies both to the M-type phospholipase A2 receptor (PLA2R) and to thrombospondin type-1 domain-containing 7A (THSD7A), initially described in adult MN, have now been identified in children and adolescents with MN and serve as a useful diagnostic and monitoring tool in this younger population as well. Whereas definitive therapy for secondary forms of MN should be targeted at the underlying cause, immunosuppressive therapy is often necessary for primary disease. Rituximab has been successfully used in the treatment of MN, and is likely effective in children with MN as well, although dosing in the pediatric population is not well established. This review highlights the new findings in adult and pediatric MN since last reviewed in this journal.
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PMID:Membranous nephropathy: diagnosis, treatment, and monitoring in the post-PLA2R era. 3181 40