Increased frequency of HLA-DRW2 in SLE.
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Biomedical subjects
Publications and source records attributed to E V Barnett.
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A sensitive direct binding radioimmunoassay (RIA) was developed which detected low avidity anti-IgG antibodies in sera negative in the latex fixation test (LFT). IgG class antibodies could be detected and were commonly found along with IgM class antibodies. Additionally, the RIA was more reproducible than the LFT, was easily adapted to measure relative avidities of anti-IgG antibodies, and had other technical advantages over the LFT.
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Polyethylene glycol (PEG) was used to isolate immune complexes from sera. Complexes were then quantified and partially characterized by a variety of immunological techniques. Complexes were detected in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Felty's syndrome and vasculitis, but not in polymyositis, scleroderma or Behçets syndrome. The level of immune complexes correlated with disease activity in SLE and RA patients. Rheumatoid factors and anti-DNA antibodies were enriched by PEG precipitation of RA and SLE sera, respectively, thus these antibodies appeared to be present in the form of soluble immune complexes. Immune complexes usually contained all three immunoglobulin classes, IgG, IgM and IgA. Complexes from RA patients were generally larger and often contained Clq, while C3 was found almost exclusively in SLE complexes which also tended to be smaller. Such compositional differences may one day explain the differences in clinical manifestations of various immune complex-mediated diseases.
Cytotoxic antibodies to B lymphocytes have been shown to be IgM. They are not absorbed by red blood cells and therefore not absorbed by red blood cells and therefore not directed against the I antigen of red cells. They are also not inhibited by mannose, as are certain natural cytotoxins against lymphocytes. Methods for producing purified eluates of IgM anti-IgM antibodies are given. These antibodies are postulated to be immunoregulative by acting on B lymphocytes.
A micro-latex fixation test (LFT) for the determination of rheumatoid factor (RF) is presented. Its advantages compared to similar tests are greater precision, simplicity, increased sensitivity, lower cost, reproducibility and adaptibility to large-scale testing. Micro-LFT titres are presented from a wide range of sample populations. The majority of normal samples show measureable titres whereas rheumatoid patients show high titres. A large sampling of pre- and post-transplant sera from kidney patients was studied and the micro-LFT titres were in the range of normal persons. The transplant sera were tested for lymphocytotoxic antibodies and no correlation was observed with the micro-LFT titres.
The metabolism of three forms of nucleic acid, native-DNA (N-DNA), single strand DNA (SS-DNA), and polyinosinic-polycytidylic acid (poly I : C), was investigated in vivo in randomly bred Swiss-Webster mice. Clearance of these substances from the circulation and tissue localization were determined at selected time intervals following the intravenous injection of 125I-labelled compounds. N- and ss-DNA were removed from the circulation more rapidly than was poly I : C. All three materials localized principally in reticuloendothelial-rich organs, i.e. liver and spleen. N-DNA was degraded by the liver more slowly than was poly I : C or ss-DNA. At 4 h following injection, the liver contained 26%, 13%, and 10% of the injected doses, respectively. Three days after injection, 4.5% of the N-DNA persisted in the liver, as compared to only 0.6% of the poly I : C, and 0.2% of the ss-DNA. The possiblity that these differences in metabolism of N-DNA, poly I: C, and ss-DNA may be related to their differing immunogenic potentials in experimental systems is discussed.
Relapsing polychondritis is a disorder of unknown cause characterized by the destruction of cartilage. To test the hypothesis that immunologic mechanisms are involved in the pathogenesis of relapsing polychondritis, we analyzed the serum of 15 patients for the presence of antibodies to cartilage. Antibodies to Type II (cartilage) collagen were found in the serum of five patients at the time of acute symptoms. No antibodies were detected either to cartilage proteoglycan or to other collagen types. The antibodies were detected at the onset of the disease and their titers appeared to correlate with severity of disease. Circulating immune complexes were also detected in the serum of these patients. Our findings support an immunologic involvement in this condition.
Mice exhibiting a spontaneous SLE-like lethal autoimmunity (female NZB/W hybrids) were given monthly doses of cyclophosphamide (CPA) 240 mg/kg p.o. starting at four months of age. Antibodies to DNA and sheep red blood cells (SRBC) were measured as well as general well being of the mice. The CPA-treated group demonstrated a marked increased in survival compared to the untreated controls with reduction of anti-DNA antibody levels but only a slight inhibition of the anamnestic response to SRBC immunization.
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Forty-seven SLE patients with severe renal disease characterized by renal biopsy documentation of diffuse proliferative or membranous glomerulonephritis or the nephrotic syndrome have been treated with azathioprine and prednisone in combination and followed for up to 12 years. Survivorship was 82% +/- 6% for five years and 74% +/- 8% for 10 years. There have been eight deaths and two patients have gone on hemodialysis. Five of the eight deaths are attributable to superinfection. Improvement in creatinine clearance was documented in 21 and decreased proteinuria in 35 of the patients. A therapeutic program, which included high dose corticosteroids initially, the combinations of azathioprine with corticosteroids chronically, and the rapid reduction in corticosteroid dosage to an alternate day schedule, appears to contribute to improved survivorship.
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The value of clinical laboratory tests as aids in diagnosis and prognosis depends on their sensitivity, specificity, and accuracy. Few tests fulfill the desirable criteria for use as screening tests in the asymptomatic, normal population. In the symptomatic patient a test of high sensitivity for detecting disease has great clinical value since a negative result tends to exclude the index diagnosis for consideration at that point in time. A test of high specificity for a single disease invariably has decreased sensitivity but has diagnostic value when positive. Data on the indirect immunofluorescent antinuclear antibody test (FANA) provide criteria to justify its wide application as a clinical laboratory test. A negative FANA result essentially excludes active systemic lupus erythematosus (SLE). Quantitation by serum titration of the positive FANA and attention to the nuclear fluorescence patterns provide indices of specificity for diagnosis of the various FANA-positive autoimmune diseases. Similarly, negative results of indirect fluorescent antibody tests for antithyroid antibodies essentially exclude Hashimoto's thyroiditis, and a negative test for antimitochondrial antibodies in biliary cirrhosis tends to exclude the surgically amenable form due to biliary stones.