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)

Recent evidence suggests that immune mechanisms can injure proliferating hematopoietic precursor cells in the bone marrow. These may involve either humoral antibody or cell-mediated cytotoxic mechanisms. Immune injury can result in a variety of bone marrow failure syndromes. Immunologically induced abnormalities or blood cell production may be restricted to a single series, such as erythrocyte or granulocyte precursors, or may involve several hematopoietic lines; clinical manifestations reflect the cell line or lines that are injured. Immune suppression of hematopoiesis has now been described in pure red cell aplasia, immune panleukopenia, systemic lupus erythematosus, atypical cases of aplastic anemia and miscellaneous other hematologic diseases.
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PMID:Immune suppression of hematopoiesis. 34 90

Pure red cell aplasia is a selective aplasia of the marrow erythroid cells. Unlike aplastic anemia, the marrow has a normal cellularity and the patients generally have normal leukocyte and platelet blood counts. The congenital form of the disease occurs in the firlst 1 1/2 years of life and is often responsive to corticosteroids. The acquired form may be secondary to infections, drugs, chemicals, or hemolytic anemia (aplastic crisis). In these cases it is often acute and self-limited with cessation of the infection or drug ingestion. It may also be secondary to systemic lupus erythematosus, rheumatoid arthritis, acute severe renal failure, severe nutritional deficiency, or diverse neoplasms, and may remit with treatment of the primary condition. When a thymoma is present, it should be resected since a remission is produced in 29 per cent of these patients. The remaining patients have an acquired primary form of the disease that tends to be chronic and in some cases may have an immune pathogenesis. A cytotoxic immunoglobulin inhibitor of the marrow erythroid cells or erythropoietin has been described and these patients may respond to prednisone and/or to cytotoxic immunosuppressive drugs such as cyclophosphamide and 6-mercaptopurine. Pure red cell aplasia appears to be more common than the literature has revealed and has stimulated much investigation into an immune pathogenesis for marrow failure.
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PMID:Diagnosis and treatment of pure red cell aplasia. 78 16

A 15 1/2-year-old girl with disseminated lupus erythematosus presented with acute flank pain and hematuria during oral anticoagulant therapy for thrombophlebitis of the lower extremities. The intravenous pyelogram demonstrated multiple filling defects of the renal collecting system interpreted as pyelocalyceal submocosal hemorrhage. This benign complication disappeared following adjustment of the anticoagulant therapy. An identical appearance has been described in a case of aplastic anemia, Henoch-Schonlein purpupa, and in renal truma. Submocosal hemorrhage of the renal collecting system is to be differentiated from pyeloureteritis cystca, uroepithelial tumor, vascular impressions from collateral circulation and submucosal edema.
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PMID:[Pyelocalyceal submucosal hemorrhage in a child treated with oral anticoagulants]. 83 63

Platelet antibodies either bound to the surface of platelets or free in the serum were sought in patients who had low platelet counts for a variety of reasons. They were detected by finding excess IgG on the surface of washed platelets either directly or after incubation of the serum with normal platelets. The technique used was a modification of that described recently (Dixon et al, 1975) in which the greater the amount of anti-IgG consumed by the reaction with platelets the less the subsequent lysis of sheep red cells coated with IgG. This test could be calibrated by adding known quantities of IgG to the antisera and thus the amount of bound IgG could be measured. Platelets from normal donors and those with thrombocytopenia due to non-immunological causes such as aplastic anaemia or acute leukaemia were found to have 15-70 ng IgG/10(7) platelets (mean 53 ng). 37 out of 38 thrombocytopenic patients in whom immune destruction of platelets was suspected were found to have excess IgG on their platelets ranging from 70 to 720 ng/10(7) (mean 297 ng, P less than 0.001) and there was a significant inverse correlation between this amount and the platelet count (r = 0.85, P less than 0.001). Antibody in the serum was found in 14 of 22 patients with 'idiopathic' thrombocytopenic purpura (ITP), three of four patients with underlying lymphoma and in all five cases of systemic lupus erythematosus (SLE). Four non-thrombocytopenic patients with autoimmune haemolytic anaemia (AIHA) due to IgG on the red cells were also studied and were shown to have no increase in platelet-bound IgG. Our results confirm the work of Dixon et al (1975) that platelet antibody as excess IgG can be readily detected on the surface of platelets in patients with immune thrombocytopenia. The clinical implications of these findings are discussed.
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PMID:Platelet antibodies in thrombocytopenic patients. 86 90

We determined platelet-associated IgG (PAIgG) levels in patients with aplastic anemia, idiopathic thrombocytopenic purpura (ITP), iron deficiency anemia, and systemic lupus erythematosus (SLE), as well as in normal healthy adults as a control group. To determine PAIgG levels, we used a competitive micro enzyme-linked immunosorbent assay, which had excellent reproducibility, recovery, and dilution. We confirmed its reliability by comparing it to the immunoradiometric assay. Both the aplastic anemia group (n = 27, mean +/- SD = 218.6 +/- 244.6 ng/10(7) platelets) and the ITP group (n = 82, mean +/- SD = 212.5 +/- 327.8 ng/10(7) platelets) had higher PAIgG levels than the SLE group (n = 4, mean +/- SD = 38.4 +/- 22.4 ng/10(7) platelets), iron deficiency anemia group (n = 10, mean +/- SD = 16.1 +/- 3.6 ng/10(7) platelets), and normal control group (n = 69, mean +/- SD = 16.1 +/- 3.6 ng/10(7) platelets. The higher platelet-associated IgG levels in aplastic anemia suggest that autoimmune mechanisms are involved.
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PMID:Elevation of platelet-associated IgG in aplastic anemia. 150 79

Evidence strongly suggests that many adverse drug reactions, including idiosyncratic drug reactions, involve reactive metabolites. Furthermore, certain functional groups, which are readily oxidized to reactive metabolites, are associated with a high incidence of adverse reactions. Most drugs can probably form reactive metabolites, but a simple comparison of covalent binding in vitro is unlikely to provide an accurate indication of the relative risk of a drug causing an idiosyncratic reaction because it does not provide an indication of how efficiently the metabolite is detoxified in vivo. In addition, the incidence and nature of adverse reactions associated with a given drug is probably determined in large measure by the location of reactive metabolite formation, as well as the chemical reactivity of the reactive metabolite. Such factors will determine which macromolecules the metabolites will bind to, and it is known that covalent binding to some proteins, such as those in the leukocyte membrane, is much more likely to lead to an immune-mediated reaction or other type of toxicity. Some reactive metabolites, such as acyl glucuronides, circulate freely and could lead to adverse reactions in almost any organ; however, most reactive metabolites have a short biological half-life, and although small amounts may escape the organ where they are formed, these metabolites are unlikely to reach sufficient concentrations to cause toxicity in other organs. Many idiosyncratic drug reactions involve leukocytes, especially agranulocytosis and drug-induced lupus. We and others have demonstrated that drugs can be metabolized by activated neutrophils and monocytes to reactive metabolites. The major reaction appears to be reaction with leukocyte-generated hypochlorous acid. Hypochlorous acid is quite reactive, and therefore it is likely that many other drugs will be found that are metabolized by activated leukocytes. Some neutrophil precursors contain myeloperoxidase and the NADPH oxidase system, and it is likely that these cells can also oxidize drugs. Therefore, although there is no direct evidence, it is reasonable to speculate that reactive metabolites generated by activated leukocytes, or neutrophil precursors in the bone marrow, could be responsible for drug-induced agranulocytosis and aplastic anemia. This could involve direct toxicity or an immune-mediated reaction. These mechanisms are not mutually exclusive, and it may be that both mechanisms contribute to the toxicity, even in the same patient. In the case of drug-induced lupus, a prevalent hypothesis for lupus involves modification of class II MHC antigens.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of leukocyte-generated reactive metabolites in the pathogenesis of idiosyncratic drug reactions. 162 36

Hematologic complications of systemic lupus erythematosus (SLE) usually involve peripheral destruction of blood cells. We report a case of aplastic anemia associated with SLE observed during the remission phase of SLE 3 months after the beginning of treatment. CD8+ T cells in the patient's bone marrow may have suppressed maturation of hematopoietic progenitor cells, which may have induced the aplastic anemia associated with SLE. Repeated therapy with high-dose methylprednisolone resulted in lasting remission.
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PMID:Aplastic anemia associated with systemic lupus erythematosus. 174 44

Aplastic anaemia is a rare complication of systemic lupus erythematosus (SLE). The mechanism is unclear but is thought to be related to an autoantibody to bone marrow precursors of haematopoiesis. We report a case of SLE related aplastic anaemia in which therapy with methylprednisolone and high dose cyclophosphamide followed by prednisolone and azathioprine resulted in complete clinical and haematological remission. Bone marrow cultures showed inhibition of erythropoiesis when incubated with acute and remission serum. Myeloid colony growth was not affected by either serum. The serum inhibitor we demonstrated was only active in vitro, and we postulate that the mechanism for marrow aplasia may have been an autoimmune cellular process.
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PMID:Aplastic anaemia in systemic lupus erythematosus: a cellular immune mechanism? 186 30

Plasma Interleukin-6 (IL-6) level was measured in patients with idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), rheumatoid arthritis and aplastic anemia. Increase in the plasma level of IL-6 was observed in patients with ITP and SLE. The plasma IL-6 level decreased with progression of the treatment for ITP, and it showed weak negative correlations with the platelet count at the onset of ITP. The increases in the plasma IL-6 level suggest the involvement of activation of the immune system in the pathogenesis of ITP.
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PMID:[Elevated plasma interleukin-6 in patient with idiopathic thrombocytopenic purpura]. 192 Aug 40

We measured the calmodulin content in platelets in 13 normal persons and in 62 patients with hematological diseases. The level of platelet calmodulin was higher in patients with idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus, myeloproliferative disorders, acute leukemia in a recovery phase, aplastic anemia, thrombosis and hypersplenism as compared to the controls. Among the patients with ITP, calmodulin was lower in responders than in nonresponders and those at the initial diagnosis. We also measured the volume, life-span and aggregation of the platelets and demonstrated a significant relationship between the calmodulin level and the platelet volume, and a negative relationship between the calmodulin level and platelet life-span, there was no correlation between the calmodulin level and platelet aggregation. We thus conclude that platelet calmodulin is inversely correlated with platelet turnover.
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PMID:Platelet calmodulin correlates with platelet turnover. 230 19


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