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)

Photopheresis, the process by which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (8-MOP), is an effective new treatment for certain disorders caused by aberrant T lymphocytes. It has become a standard therapy for advanced cutaneous T cell lymphoma and shows promise in the treatment of four autoimmune disorders (pemphigus vulgaris, the progressive systemic sclerosis form of scleroderma, rheumatoid arthritis, systemic lupus erythematosus) and in reversal of immunologic rejection of transplanted organs. Positive immunologic alterations observed in patients with AIDS-related complex merit further investigation, and preliminary trials in the management of patients with multiple sclerosis, myasthenia gravis and autoimmune insulin-dependent diabetes mellitus have recently been initiated. The inability of the treatment to meaningfully alter the course of the B cell malignancy, chronic lymphocytic leukemia, suggests that B cell proliferations, at least those involving malignant cells, may be more resistant to this treatment. The mechanism of action of photopheresis is likely to be multifaceted, but at least in experimental systems appears to involve an immunization against the pathogenic T cells, in a highly specific manner. Photoactivated 8-MOP initiates a cascade of cellular events by forming covalent photoadducts with nuclear DNA, with cell surface molecules and possibly with other cytoplasmic components of the ultraviolet exposed leukocytes. For reasons not yet clear, exposure of populations of T cells containing expanding a clone(s) of pathogenic T cells to photoactivated 8-MOP alters these cells so that their reinfusion induces a therapeutically significant immunologic reaction that targets unirradiated T cells of the same pathogenic clone(s). It is suggested that the specificity of the induced immunologic reaction may result, in sequence, from the exquisitely titratable damage that 8-MOP inflicts upon cells of the pathogenic clone(s), the return of these cells to an immunocompetent individual, the removal of the photo-damaged cells from the blood by the reticuloendothelial system and the preferential induction of an immune response against cells of the pathologically expanded clone(s).
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PMID:Photopheresis: a clinically relevant immunobiologic response modifier. 179 5

(C57BL/6 x DBA/2)F1 (B6D2F1) mice inoculated with parental DBA/2 (D2) splenocytes develop chronic stimulatory graft-versus-host reaction with many of the clinical manifestations of systemic lupus erythematosus. This investigation tested the ability of 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) light-treated D2 cells, primed to contain an expanded population of T cells specific for B6D2F1 major histocompatability complex antigens, to treat and/or prevent such systemic lupus erythematosus-like disease. 8-MOP/UVA-treated cells from B6D2F1-primed D2 donors were inoculated into B6D2F1 recipients weekly six to ten times, either before or after initiating graft-versus-host disease with normal D2 cells. A third group of B6D2F1 recipients were vaccinated weekly six times before disease initiation using 8-MOP/UVA-attenuated, B6D2F1-primed D2 cells that had been secondarily stimulated and expanded in vitro in the presence of irradiated B6D2F1 targets and interleukin-2. Control B6D2F1 mice were vaccinated with 8-MOP/UVA-treated D2 cells stimulated in vitro and/or in vivo with (C3H/HeJ x DBA/2)F1 cells. Only mice vaccinated with 8-MOP/UVA-attenuated D2-anti-B6D2F1 cells that were secondarily stimulated and expanded in vitro exhibited differences from controls when measured by the clinical parameters of ascites formation, and mean survival (p < 0.025). These groups also differed significantly in mean antinuclear antibody titer measured 14 weeks after disease initiation (p < 0.05). At 28 weeks, histologic evidence of systemic lupus erythematosus-like kidney disease was found only in the control group. These results indicate that photochemically attenuated D2-anti-B6D2F1 cells primed in vivo and secondarily stimulated and expanded in vitro are capable of vaccinating recipients against progression of graft-versus-host reaction-initiated systemic lupus erythematosus-like disease.
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PMID:Specific suppression of lupus-like graft-versus-host disease using extracorporeal photochemical attenuation of effector lymphocytes. 782 72

A 41-year-old female was admitted to our hospital with acute renal failure. The renal biopsy showed focal necrotizing crescentic glomerulonephritis, and her serology revealed a high titer of MPO-ANCA. The diagnosis of MPO-ANCA-associated microscopic polyarteritis was made, and her basic illness proved to be systemic lupus erythematosus (SLE) because of renal injury, polyarteritis, pancytopenia, anti-double-strand DNA antibody, and anti-nuclear antibodies. After treatment with prednisolone (PSL) and cyclophosphamide, her renal function improved and her MOP ANCA titer was lowered. After 2 years, she was readmitted due to dyspnea. Chest X-ray and echocardiography revealed pericarditis and bilateral pleural effusion. Renal biopsy was carried out again because of an increase in MPO-ANCA, which showed minor abnormalities. PSL therapy led to remission of pericarditis, resulting in a decrease in MPO-ANCA. In this case, MPO-ANCA is likely to be associated not with the activity of polyarteritis, but with that of SLE, and care should be taken in evaluating the clinical usefulness of MPO-ANCA in cases with SLE.
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PMID:[Renal microscopic polyarteritis replaced by pericarditis with episodic increases in MPO-ANCA in a patient with systemic lupus erythematosus]. 989 59