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Thrombotic microangiopathy in anti-glomerular basement membrane glomerulonephritis.

A review was made of the clinical histories, treatment, and renal histologic features of 12 patients with anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM disease). Two patients had milder histopathologic changes in their kidney biopsy specimens and achieved clinical remission. The other ten patients with severe lesions in their biopsy specimens progressed to renal failure. In addition, vascular lesions of thrombotic microangiopathy were present in six of 12 patients. Six patients had clinical laboratory evidence of microangiopathic hemolytic anemia. There are two important points to be noted from this study. First, the kidney biopsy specimen may be a useful indicator of disease severity and prognosis. Second, clinical laboratory or histologic evidence of thrombotic microangiopathy may occur in 75% of patients with anti-GBM disease.

Adolescent↗

[Electron microscopic and immunohistologic studies of patients with Horton's temporal arteritis].

Temporal arteritis is a systmic disease with a predilecation for the cranio-temporal vascular area. Histologically it is a panarteritis. Diagnosis is based on the presence of lymphocytes, histiocytes and foci of epitheloid cells in the media of the temporal artery. The presence of giant cells is, however not obligatory. The present study emphasizes the value of biopsy of the temporal artery in diagnosing this disease. It, furthermore, also points out the 10-percent possibility of false negative biopsy results based on patchy vascular lesions. Tenderness to touch of the temporal artery, characteristic of temporal arteriitis, can be explained by perineural inflammatory infiltration of nerves in the adventitia of this artery. Examination under the electron microscope reveals almost complete destruction of the smooth muscles of the media by epitheloid cell granulomas. Massive neogenesis of collagen ensues. Furthermore, numerous myofibroblasts, macrophages and histiocytes are observed. Several macrophages close to each other create the impression of giant cells in the light microscope. The electron microscope image allows for clear differentiation between temporal arteritis on one hand and of arteriosclerosis on the other. Using the immunoperoxidase method in temporal arteritis, immune globulines are found intracellularly in plasma cells. Extracellularly, however, neither immune golbulins nor complement deposits are found in the vascular wall. Thus, the assumption that temporal arteritis represents a immune complex disorder cannot be maintained. The most frequent ophthalmologic complication in temporal arteritis is ischemic optic neuropathy. Histologic examination of a bulbus presenting anterior ischemic optic neuropathy in a case of temporal arteritis revealed predominantly lymphocytic infiltrations of the short and long ciliary arteries. No inflammatory infiltration was found in the central retinal artery. The development of anterior ischemic optic neuropathy can be explained by impaired perfusion or by occlusion of the short posterior ciliary arteries. In 60% of patients suffering from temporal arteritis, we found anticollagen antibodies in the serum. Collagenization of the vascular wall as observed in our electron-microscopic examinations must, therefore, be considered the paradoxical consequence of an immune reaction caused by collagen auto-antibodies. Collagen auto-antibodies play a decisive role in the maintenance and chronicity of the inflammatory process in temporal arteritis. In therapy, corticosteroids should not be administered according to rule but rather in doses adjusted to individual requirements.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Statistical analysis of five immune complex screening assays: patterns of detection in patients with rheumatoid arthritis, systemic lupus erythematosus, infectious endocarditis, and diabetes mellitus.

A comparative study of four nonspecific screening techniques (direct nephelometry, PEG-C4, PEG-IgG, and radiolabeled Clq binding) for immune complexes (IC) and of a technique specific for the detection of insulin-anti-insulin IC was undertaken in four groups of patients with diagnosis of infectious endocarditis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and diabetes. The highest frequency of positive results was given by the PEG-IgG test in RA, the Clq-binding test in SLE, the insulin-anti-insulin IC screening test in diabetes, and the PEG-IgG and Clq-binding tests in infectious endocarditis. Of the four nonspecific tests, the PEG-C4 assay appeared to be the least discriminative, since it failed to show significant differences between any group of patients and the group of controls. Direct nephelometry, PEG-IgG, and radiolabeled Clq binding gave consistently higher results in RA than in other diseases, and in this disease the rates of agreement between these tests were highly significant. Significant agreements between the rates of positivity of Clq binding and PEG-IgG tests were seen in all groups of patients studied. Spearman's analysis of rank showed the best correlations among tests based on similar principles (ie, PEG precipitation), and also a strong correlation between Clq binding and the PEG-IgG test in RA. The PEG-IgG test appears to be a reliable IC screening test for general use with the advantage of not involving radioisotopes. In regard to antigen-specific tests, although their specificity and sensitivity may be high, their results may show no correlation with nonspecific screening tests nor with the presence or absence of clinical or laboratory abnormalities suggestive of IC deposition, as exemplified by the insulin-anti-insulin IC screening test in diabetic patients.

Antigen-Antibody Complex↗

An enzyme-linked immunoassay for detection of IgG- and C3-containing circulating immune complexes: comparison with a radioimmunoassay and quantitation in patients with rheumatic diseases.

We developed a simplified, relatively rapid, inexpensive, antigen-nonspecific, enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG)- and C3-containing circulating immune complexes (CICs), adapted from a solid-phase anti-C3 radioimmunoassay (RIA). Standards (containing purified, heat-aggregated IgG and fresh human serum) or samples were allowed to react with goat F(ab')2 antihuman C3 bound to the matrix of microtiter plates. Then alkaline phosphatase conjugated to goat IgG fraction antihuman IgG was added, followed by p-nitrophenylphosphate, optical densities determined, and concentrations of CICs calculated. We found excellent correlations between serum and plasma CIC levels by either ELISA (r = 0.95, p less than 0.01) or RIA (r = 0.89, p less than 0.01). Furthermore, ELISA quantitation of CICs correlated well with RIA (serum, n = 75, r = 0.64, p less than 0.01; plasma, n = 101, r = 0.56, p less than 0.01). By ELISA we found 32 normal subjects had 38 +/- 12 micrograms CIC/ml in serum and 34 +/- 10 micrograms CIC/ml in plasma. Patients with systemic lupus erythematosus (39% of 27 patients, p less than 0.05) had significantly elevated CIC levels compared with normal (serum, 157 +/- 50 micrograms/ml, p less than 0.01; plasma, 89 +/- 23 micrograms/ml, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Antibody Complex↗

An immunochemical study of the synovial fluid can contribute to the distinction between rheumatoid and non rheumatoid arthritis.

Synovial fluids from 102 patients affected by various joint diseases have been analyzed for their protein, immunoglobulin and beta 2-microglobulin contents, for the total and alternative pathway hemolytic activities of the complement components, for the presence of rheumatoid factors and Clq binding materials. The aim of this study was to verify whether an immunochemical analysis of the synovial fluid could help to distinguish rheumatoid arthritis from other arthropathies. With regard to this, we emphasize that the latex test, the Clq binding assay, as well as the measurement of C3d and beta 2-microglobulin concentrations in synovial fluids, were the most helpful assays. An immunochemical synovial score was calculated summing the results of these four tests, thus making the recognition of rheumatoid arthritis, among the various inflammatory joint diseases, easier.

Arthritis↗

Selective complete Clq deficiency associated with systemic lupus erythematosus.

We report a case of systemic lupus erythematosus (SLE) and recurrent infections associated with isolated Clq deficiency. A 17-year-old girl from Saudi Arabia was hospitalized with seizures, fever, arthralgia, hair loss, oral ulceration and skin rash. Clinical and laboratory findings fulfilled the ARA preliminary criteria for the classification of SLE. Nonlesional skin contained immunoglobulins and C3 at the dermal-epidermal junction. She did not have antibodies to DNA or low C3 or C4. Total serum hemolytic complement activity was absent due to a total selective absence of Clq. There was no circulating inhibitor of Clq activity. The published experience of isolated selective complete Clq deficiency associated with clinical disease is reviewed.

Adolescent↗

Immunologic techniques utilized in the diagnosis of occupational lung disease.

Humoral and/or cell-mediated immune responses may contribute to the tissue injury in patients with certain types of occupational asthma, hypersensitivity pneumonitis, silicosis, and asbestosis. Numerous diagnostic modalities are available to the clinician investigating the etiology of these disorders. Among the current immunologic techniques discussed in this article are immunoassays for specific anti-IgE antibody, gel diffusion reactions, immunoelectrophoresis, ANA assays, complement studies, and immune complex assays.

Antibodies, Antinuclear↗

Murine lupus nephritis. Effects of glucocorticoid on circulating and tissue-bound immunoreactants.

We investigated the effects of methylprednisolone on immunoreactants of plasma and kidney to determine factors that might be relevant to the arrest of murine lupus nephritis. At the onset of nephritis, at about 5 months of age, the mice were divided in two groups and received either methylprednisolone or saline injections for 12 weeks. Before and after therapy (or saline injections), we determined the concentrations of plasma IgG, complement (C3), anti-DNA antibodies, Clq-reactive materials, creatinine, and urea nitrogen; in the kidneys, we assessed the relative distribution of IgG, IgM, and C3 in glomeruli, and we determined the concentration of IgG and anti-DNA activity of the eluted proteins. Our results indicated that methylprednisolone administered at the onset of nephritis preserved glomerular structure and function by decreasing the amount of tissue-bound immunoreactants and by inducing a preferential localization of immunoreactants in mesangia. Of the immunoreactants studied in plasma, a decreased concentration of IgG, but not the concentrations of anti-DNA antibodies, C3, and Clq-reactive materials, was associated with the arrest of nephritis. The anti-DNA activity in the renal eluates was very low and comparable in treated and untreated mice. Immune complex systems other than, or in addition to, DNA-anti-DNA likely play a role in the pathogenesis of murine lupus nephritis.

Animals↗

Circulating immune complexes in myocardial infarction.

Thirty-one patients with proven acute myocardial infarction (MI) were studied prospectively at the time of admission to hospital and at 3, 7 and 18 days using 4 immune complex (IC) assays. Each assay showed an increased incidence of IC activity in MI with 76% of patients being positive in at least 1 assay on one or more of the sampling days. A positive IC assay did not show a significant correlation with cardiac failure, pericarditis, post MI syndrome or previous infarction. The presence of IC was found to correlate with serum C-reactive protein (CRP), serum enzymes and ESR and suggested that complexed CRP or other acute phase proteins may account for some of the IC activity found with less specific assays. The measurement of IC levels in MI has not proved helpful in the diagnosis, management or prediction of outcome in this disorder.

Antigen-Antibody Complex↗

Circulating immune complexes containing IgG, IgA and IgM in patients with myocardial infarction: detection with C1qSP and anti C3SP.

Immunological reactions have been recognized in cardiac disease and immune complexes (ICs) have been suggested to be of pathogenetic significance in the occurrence of post-myocardial infarction syndromes. ICs of IgA, IgG, IgM class have been detected in myocardial infarction utilizing a C1qSP and an anti C3 assay. A poor concordance was found between the two methods. Early pericarditis was found to be associated with the presence of ICs, suggesting that ICs may play a role in developing pericarditis or that they may be considered a marker of pericarditis by an immunological mechanism.

Aged↗

Antibody-independent interactions between Escherichia coli J5 and human complement components.

With the characterization of an increasing number of molecules that are capable of activating the 1st component of the classical pathway of complement (C), the possibility that some Gram-negative bacteria may activate C1 independent of naturally occurring antibody has been reexamined. We have confirmed a previous report that purified C1 (the activated form of C1) can bind to certain strains of bacteria and it retains its enzymatic activity when thus bound. The availability of purified C1 in its precursor form has allowed us to extend these observations to the native C1 molecule. Using a semirough mutant of Escherichia coli, the galactose epimerase-deficient strain E. coli J5, we have examined the binding and activation of radiolabeled C1. J5 bound radiolabeled C1 in a dose-dependent manner and essentially all of the bound C1 was activated as judged by SDS-PAGE. The bacteria-C1 complex consumed purified C4 and C2 and the consumption of C2 was proportional to the C4 concentration. Subsequent addition of terminal C components C3-9 supplied as serum-EDTA caused a highly significant decrease in bacterial viability. These results demonstrate that C1 may bind to the bacterial membrane in such a manner as to initiate a bactericidal reaction. Therefore, antibody-independent binding and activation of C1 must be considered in the assessment of serum sensitivity of Gram-negative bacteria.

Animals↗