Anticardiolipin antibody associated with renal carcinoma.
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Biomedical subjects
Publications and source records attributed to Z Sthoeger.
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A 58 year old woman developed systemic symptoms, interstitial lung disease, splenomegaly, leukopenia and anti-histone and anti-nuclear antibodies (ANA), while treated with hydralazine for hypertension. Five months after presentation she was admitted with high fever, skin rash and atypical lymphocytosis due to acute cytomegalovirus (CMV) infection. Worsening leukopenia and increased ANA were found, and high titres of anti-DNA antibodies, anti-cardiolipin antibodies and rheumatoid factors appeared. Hydralazine was stopped and the patient gradually became asymptomatic. All autoantibodies spontaneously disappeared (over 16 weeks), and the white cell count and spleen size became normal. The patient was found to be a slow acetylator and to have both HLA-DR4 and selective IgA deficiency. Thus, a multifactorial genetic susceptibility to develop drug-induced lupus was brought out in stages first by hydralazine and then by CMV, yet all manifestations and autoantibodies resolved spontaneously, demonstrating the complex interplay of varied environmental factors with a genetic predisposition in the pathogenesis of autoimmunity.
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OBJECTIVE: To elucidate the role of anticardiolipin antibodies (aCL) in the pathogenesis of hemolytic anemia in patients with systemic lupus erythematosus (SLE). METHODS: Immunoglobulins (Ig) and cardiolipin reactivity were evaluated in red blood cell (RBC) eluates and in the sera of patients with SLE and controls by a solid phase enzyme linked immunosorbent assay. RESULTS: aCL were detected in sera of 2 patients with SLE with active hemolytic anemia. The RBC eluates of these patients contained Ig (mainly IgG) with significant cardiolipin reactivity. RBC eluates from healthy volunteers failed to demonstrate measurable amounts of Ig whereas Ig eluted from RBC of chronic lymphocytic leukemia patients with active hemolysis but no aCL did not react with cardiolipin. Furthermore, under treatment, one patient went into complete remission with resolution of the hemolysis, negative Coombs' tests and lower serum aCL. The other patient, however, continued to demonstrate both high sera aCL and positive Coombs' tests. CONCLUSION: aCL may play a direct role in the pathogenesis of hemolytic anemia in some patients with SLE by acting as anti-RBC autoantibodies.
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The cDNA for human beta 2-interferon (IFN-beta 2)/B-cell differentiation factor 2/hepatocyte-stimulating factor was expressed in Escherichia coli to yield a fusion protein which contains the 182 carboxyl-terminal amino acids of IFN-beta 2 fused to a 34-amino acid prokaryotic leader peptide (rIFN-beta 2). When added to cultures of human hepatoma cell line Hep3B2, rIFN-beta 2 as well as preparations of natural IFN-beta 2 enhance secretion of positive acute phase reactants such as alpha 1-antichymotrypsin, complement C3, fibrinogen, and alpha 1-acid glycoprotein and inhibit secretion of albumin, confirming that a protein derived from the IFN-beta 2 gene can have hepatocyte-stimulating factor activity. We have prepared a rabbit polyclonal antiserum to the E. coli-derived human IFN-beta 2 fusion protein. This polyclonal antiserum inhibits the hepatocyte-stimulating and B-cell differentiation activities of appropriate IFN-beta 2 preparations. The anti-rIFN-beta 2 antiserum has been used in immunoprecipitation experiments and in Western blots to help define the secretory proteins derived from the IFN-beta 2 gene in fibroblasts and monocytes. "Uninduced" human FS-4 fibroblasts as well as those induced with interleukin-1 alpha, tumor necrosis factor, or bacterial lipopolysaccharide secrete at least five forms of IFN-beta 2 of apparent molecular mass in the range from 23 to 30 kDa which can be resolved by polyacrylamide gel electrophoresis under denaturing and reducing conditions. The three higher molecular mass forms are not observed when FS-4 cells are induced in the presence of tunicamycin, suggesting that these forms are N-glycosylated (gp28, gp29, and gp30). Although secretion of the two lower molecular mass forms is resistant to tunicamycin, they are labeled by [3H]glucosamine (gp23-gp25). The inclusion of cycloheximide during the [35S]methionine labeling of induced FS-4 cells results in the preferential synthesis and secretion of the 29-kDa triplet. Human monocytes induced with bacterial lipopolysaccharide also secrete several distinct forms of IFN-beta 2 in the size range from 23 to 30 kDa which co-migrate in polyacrylamide gels with those obtained from FS-4 cells. Our observations help relate previous descriptions of multiple forms of hepatocyte-stimulating factor to specific proteins derived from the IFN-beta 2 gene.
The human beta 2 interferon (IFN-beta 2) gene, a gene that also codes for B cell differentiation factor 2 (BSF-2), plasmacytoma/hybridoma growth factor (HGF), and hepatocyte-stimulating factor (HSF), is expressed in a variety of lymphoid and nonlymphoid tissues. Endotoxin, or bacterial lipopolysaccharide (LPS) preparations derived from the outer membrane of Escherichia coli or Salmonella typhimurium rapidly elevate IFN-beta 2 mRNA level in human skin fibroblasts (FS-4 strain). E. coli-derived LPS enhances IFN-beta 2 mRNA expression in FS-4 fibroblasts at a concentration as low as 0.3 ng/ml; this response is near-maximal in the range of 0.1-1 microgram/ml LPS. The increase in IFN-beta 2 mRNA level caused by LPS in FS-4 cells is detected within 30 min after addition of LPS, is sustained for at least 20 h thereafter, appears to involve the protein kinase C signal transduction pathway, does not require new protein synthesis, and is inhibited by dexamethasone in a dose-dependent fashion (in the range 10(-6)-10(-8) M). Cultures of LPS-treated FS-4 cells exhibit an antiviral state against vesicular stomatitis virus, which can be prevented by anti-IFN-beta antiserum. Medium obtained from LPS-treated FS-4 cell cultures enhances the number of immunoglobulin-secreting cells in cultures of human B-lymphoblastoid (CESS) cells. Thus, LPS may trigger a number of host defense mechanisms in the course of infection due to Gram-negative bacteria by enhancing IFN-beta 2 production by the ubiquitous fibroblast.
We present a case history of a woman who developed dermatomyositis following the diagnosis of stage IV ovarian cancer. Dermatomyositis is a rare paraneoplastic syndrome that usually precedes the diagnosis of ovarian cancer by several months or years. Ours is the fifth reported case of dermatomyositis after an established diagnosis of ovarian cancer in the literature.
We conducted a retrospective serosurvey of 1,000 persons in Israel who had fever of undetermined cause to look for Ehrlichia chaffeensis antibodies. Four of five cases with antibodies reactive to E. chaffeensis were diagnosed in the summer, when ticks are more active. All patients had influenzalike symptoms with high fever. None of the cases was fatal. Three serum samples were also seroreactive for antibodies to E. canis, and one was also reactive to the human granulocytic ehrlichiosis (HGE) agent. The titer to the HGE agent in this patient was higher than the serum titer to E. chaffeensis, and the Western blot analysis also indicated that the HGE agent was the primary cause of infection. We present the first serologic evidence that the agents of human monocytic ehrlichiosis (HME) and HGE are present in Israel. Therefore, human ehrlichiosis should be included in the differential diagnoses for persons in Israel who have been exposed to ticks and have influenzalike symptoms.