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Biomedical subjects

A Wiik

Publications and source records attributed to A Wiik.

At least 109 records · Page 6Linked to original sources

The specificity of anti-cardiolipin antibodies from syphilis patients and from patients with systemic lupus erythematosus.

In order to elucidate the fine specificity of anti-cardiolipin antibodies (ACA) in patients with SLE compared to patients with syphilis (SY) various inhibition experiments were performed. Seven SLE sera and eight SY sera positive for ACA were diluted and preincubated with either cardiolipin VDRL-antigen, mitochondial particles, dsDNA, ssDNA or dilution buffer. The sera were subsequently assayed for residual ACA activity of IgG or IgM class using a sensitive ELISA technique. Significant inhibition of IgM ACA activity in SLE sera was found with cardiolipin, VDRL-antigen and mitochondrial particles. Cardiolipin inhibited binding to a significantly higher extent than the other antigens. In SY sera significant inhibition of the IgM ACA activity was found with all antigens used. The strongest inhibition was seen using VDRL-antigen. Inhibition of IgG ACA activity could only be clearly estimated in SY sera where VDRL-antigen was found to be a much stronger inhibitor than the rest, purified cardiolipin being the weakest. Only two out of seven SLE sera were IgG ACA positive which made a clear conclusion impossible but a strong inhibitory capability of pure cardiolipin and a weaker inhibition with VDRL-antigen was found. This study disclosed a difference between SLE and SY sera showing strong reactivity of ACA in SLE sera with purified cardiolipin, contrasting to ACA in SY sera which predominantly reacted with cardiolipin in the liposome environment, as found in the VDRL-antigen and in mitochondrial particles.

Antibody Specificity↗

Spontaneous and induced immunoglobulin synthesis and anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis: relation to leukocyte subpopulations in blood and active lesions.

Using a reverse plaque forming cell (PFC) assay the production of immunoglobulin (Ig) by peripheral blood mononuclear cells (MNCs) in vitro was studied in 12 patients with Wegener's granulomatosis (WG). Spontaneous IgG production was increased in two of six untreated patients. The IgG response of MNCs from eight untreated patients to pokeweed mitogen (PWM) and Epstein-Barr virus (EBV) stimulation was significantly depressed. The IgM and IgA production followed the individual pattern of IgG. Blood B-cell and T-cell subset concentrations were normal before therapy, whereas the monocyte concentration was increased in four of six patients. Titers of anti-neutrophil cytoplasm autoantibodies (ANCAs) did not correlate with spontaneous or induced Ig production nor with blood leukocyte subset concentrations. Biopsy specimens from upper respiratory tract lesions in seven untreated patients showed numerous macrophages, activated T lymphocytes, and plasma cells, suggesting a pathogenetic role of these cells in the development of lesions and local production of ANCAs.

Antibodies↗

Interleukin 1-induced down-regulation of antibody binding to CD4 molecules on human lymphocytes.

Interleukin 1 (IL-1) is involved in the early activation of T lymphocytes. The CD4 antigen, described as a phenotypic marker of helper T cells, is also important in early T-cell activation by its ability to bind to MHC class II molecules on antigen-presenting cells, and to transmit positive (and negative) signals to the cells. We observed that purified human monocyte IL-1 as well as recombinant IL-1 alpha and IL-1 beta selectively decreased the binding of monoclonal antibodies to CD4 on the surface of otherwise unstimulated blood T cells, in contrast to prestimulated and continuously grown CD4+ cells. Under optimal growth conditions, the initial reduction in antibody binding to CD4 was followed by an apparent re-expression of the CD4 antigen even in the presence of high concentrations of IL-1. This re-expression did not occur if the cells were cultured at 4 degrees C, or after treatment with actinomycin D or cytochalasin B, indicating that protein synthesis and intact microfilament function were essential for re-expression of CD4 binding. The mechanism by which CD4 molecules are physically and/or functionally modulated by IL-1 is unclear.

Antibodies, Monoclonal↗

Anti-corticosteroid antibodies in AIDS patients.

Patients suffering from AIDS tend to have symptoms that resemble those encountered in adrenocortical insufficiency. Serum sodium concentrations and blood pressure values were monitored and found to be subnormal, despite the fact that renin activity and aldosterone levels were either normal or elevated. We report the presence of autoantibodies directed against hydrocortisone among such AIDS patients. Indirect immunofluorescence technique using patients' sera and adrenal glands from AIDS patients as antigen showed antibodies to adrenocortical cells in sera from 9 of the 12 AIDS patients and in none from patients with autoimmune diseases and viral diseases or healthy blood donors. No similar reaction was seen in normal human or monkey adrenal glands. An ELISA technique was developed using hydrocortisone as antigen and using this technique 45% of the AIDS patients were found to have antibodies to hydrocortisone. It is possible that anti-corticosteroid antibodies (ACSA) may play a role in the pathophysiology of the Addison's like syndrome seen in terminal phases of AIDS.

Acquired Immunodeficiency Syndrome↗

Autoantibodies to the mitotic spindle apparatus in Mycoplasma pneumoniae disease.

Antibodies to the mitotic spindle apparatus (MS) have been detected in only a very few patient sera studied for antinuclear antibodies by routine screening (G. A. McCarty, D. W. Velencia, and M. J. Fritzler, J. Rheumatol. 11:213-218, 1984). We found anti-MS antibodies to be quite common in sera from patients with Mycoplasma pneumoniae, especially in those who developed cold agglutinins (71%). Absorption experiments indicated that the formation of anti-MS antibodies is not triggered by epitopes on the M. pneumoniae surface. These antibodies were distinct from cold agglutinins, antibrain antibodies, and smooth-muscle antibodies. All patients previously reported to harbor anti-MS had clinical features compatible with a diagnosis of systemic lupus erythematosus, rheumatoid arthritis, or an evolving connective-tissue disorder. Such systemic disorders might develop in a small proportion of patients who have had M. pneumoniae illness.

Autoantibodies↗

A Danish inter-laboratory study of IgM rheumatoid factor (RF) determined by enzyme-linked immunosorbent assay (ELISA).

The present report concerns data on the applicability of a standardized IgM RF ELISA as undertaken in five laboratories in Denmark. The study was done upon the initiative of the Danish Association for Clinical Immunology who wished to get an impression of the inter-laboratory reproducibility of the assay, since several Counties in Denmark had de-centralized the IgM RF technique for economic reasons. All laboratories received a form describing the details of the recommended technique, a preparation of human IgG for coating of the microplates, a national standard preparation of IgM RF, 3 well-known control sera and 6 unknown patient sera from the Laboratory for Autoimmune Serology. The results were estimated in IU/ml, calculated in each laboratory. Coefficients of variation in positive sera were between 13 and 25%, and in negative sera 45-50%. Negative sera could always be clearly distinguished from low, middle and highly positive sera. Day-to-day variation was minimal in all laboratories (6%-13%). The IgM RF ELISA technique could thus be handled in all laboratories rendering reasonably reproducible results, and all laboratories could distinguish sera with low, intermediate and high levels of the antibodies from each other and from negative sera.

Enzyme-Linked Immunosorbent Assay↗

Systemic lupus erythematosus: follow-up study of 148 patients. I: Classification, clinical and laboratory findings, course and outcome.

The present paper is a description of 148 patients with circulating antinuclear antibodies and multisystemic disease filed during 18 years by one of the authors and followed up to date in 1981-83. Seventy-eight per cent of the patients satisfied the 1971 ARA criteria for the classification of systemic lupus erythematosus and 92 per cent fulfilled the 1982 ARA criteria. Eighty-five per cent were women, the mean age at onset of SLE was 32 years. Malar rash and arthritis were early manifestations in 80 per cent of the patients whereas the onset of nephropathy, CNS manifestations, serositis, and peripheral cytopenia was delayed in about half of the patients. Nephropathy and thrombocytopenia were observed particularly in the youngest patients. The mean duration of the observation period was 8 years. The 10-year-survival was 80 per cent. Half of the deaths were presumably unrelated to SLE. The mean ages at entry of patients who died of SLE and of unrelated causes were 30 and 52 years respectively. Eighteen per cent of the deaths were caused by uremia and 18 per cent by infections. The total and the SLE related mortalities were evenly distributed throughout the observation period. The morbidity (incidence of new ARA criteria and other findings indicating active disease) decreased during the first year of observation but rarely subsided completely during the following years. All patients observed for more than 10 years showed evidence of active disease during the rest of the observation period and most showed evidence of renal disease.

Adolescent↗

Systemic lupus erythematosus. Follow-up study of 148 patients. II: Predictive factors of importance for course and outcome.

The predictive value of a number of clinical and laboratory variables for the mortality of 148 patients with systemic lupus erythematosus (SLE) with a mean observation period of 8 years and a 10-year-survival of 80 per cent was calculated by means of differentiated survival rate analyses and stepwise regression analyses. The predictive power of several variables increased if the calculations were based on deaths caused by SLE rather than on the total mortality rate. The survival rate decreased after 1973 because a diagnosis of SLE was made in some patients with terminal disease who would have remained without a diagnosis before that time. The causes of death and the treatment were identical before and after 1973. The presence of a high number of diagnostic ARA criteria within the first year of observation was a predictor of decreased survival. Severe but non-fatal infections (meningitis, septicemia, pneumonia) significantly reduced the survival rate. Patients with proteinuria and azotemia, within the first 2 years of observation, had a 10-year-survival of 70 per cent. The survival of patients with CNS manifestations was not significantly reduced. The butterfly rash and the presence of lymphopenia were predictors of decreased survival, whereas the presence of DNA antibodies had no predictive value for survival.

Adolescent↗

Release of leukotriene B4 and 5-hydroxyeicosatetraenoic acid during phagocytosis of artificial immune complexes by peripheral neutrophils in chronic inflammatory bowel disease.

The capacity of peripheral neutrophils for activation of the arachidonic acid (AA) metabolism was studied during phagocytosis of IgG containing immune complexes (ICs) binding to Fc-receptors. Release of approximately 9% of the intracellular pool of radiolabelled AA in phospholipids, and release of the pro-inflammatory mediators, leukotriene B4 (LTB4), constituting 1.8%, and 5-hydroxyeicosatetraenoic acid (5-HETE), constituting 2.9% of the total radioactivity released, were demonstrated in 15 patients with untreated Crohn's disease, 15 patients with ulcerative colitis, and in 15 healthy volunteers. The concentrations of LTB4 and 5-HETE released were within the range of chemotactic activity for the two lipoxygenase products. Multiple large IgG containing ICs were revealed in neutrophils after phagocytosis by immunofluorescence. A minor defect in the IC uptake in patients with Crohn's disease observed in the absence of complement only, did not result in a subnormal activation of arachidonic acid release or metabolism. The study suggests that complexes of the IgG-class previously demonstrated in chronic inflammatory bowel disease, particularly in Crohn's disease, may activate inflammatory neutrophils leading to release of significant amounts of the pro-inflammatory lipoxygenase metabolites, LTB4 and 5-HETE.

Adult↗

High prevalence of anti-mitochondrial antibodies among patients with some well-defined connective tissue diseases.

A sensitive enzyme linked immunosorbent assay for determination of low levels of anti-mitochondrial antibodies (AMA) has been developed. With this method, sera from patients with primary biliary cirrhosis (PBC) and patients with different connective tissue diseases were investigated. Ninety percent of PBC sera were found to harbour high levels of AMA and a high proportion of patients with systemic lupus erythematosus (SLE), but also other patients with connective tissue diseases were found to have low affinity or low concentrations of AMA in their sera. AMA positive sera were further investigated with sodium dodecyl sulphate polyacrylamide gel electrophoresis and immunoblotting technique. PBC showed reactivity to 70, 50 and 45 kD mitochondrial polypeptides. SLE sera showed reactivity to 70 and 45 kD polypeptides and furthermore to a 65 kD polypeptide. Many of the AMA positive sera from patients with connective tissue diseases reacted to a 65 kD polypeptide.

Arthritis, Rheumatoid↗

Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis.

Immunoglobulin G (IgG) autoantibodies against extranuclear components of polymorphonuclear granulocytes were detected in 25 of 27 serum samples from patients with active Wegener's granulomatosis and in only 4 of 32 samples from patients without signs of disease activity. In a prospective study of 19 patients these antibodies proved to be better markers of disease activity than several other laboratory measurements used previously. The autoantibodies were disease specific and the titres were related to the results of an in-vitro granulocyte phagocytosis test, in which 7S IgG antibodies were internalised after specific binding to the cell, resulting in gradual formation of ring-like cytoplasmic structures. This autoantibody may have a pathogenetic role in Wegener's granulomatosis. The detection of this antibody is valuable for diagnosis and estimation of disease activity.

Adult↗

Demonstration of circulating immune complexes by the indirect leucocyte phagocytosis test in chronic inflammatory bowel disease. Relation to results of a standard complement consumption assay.

Circulating immune complexes were studied in untreated Crohn's disease (CD) and ulcerative colitis (UC) by leucocyte phagocytosis. Neutrophils from normal donors took up large immunoglobulin-containing inclusions from 14 of 15 CD sera, 3 of 15 UC sera (p less than 0.002) and from none of 15 reference sera from healthy volunteers (p less than 0.002). In contrast, inclusions could not be demonstrated on direct microscopic investigation. Our study confirms the presence of circulating immune complexes in Crohn's disease. Predominance of IgG-containing complexes in this condition is consistent with a mucosal origin. Discrepant results obtained by direct examination and by incubation of sera from patients with normal test neutrophils suggest a defective immune complex phagocytosis in CD. In consistency with this possibility, control experiments revealed a markedly decreased complex uptake by neutrophils of CD patients in vitro.

Antigen-Antibody Complex↗

Immunoglobulins, anti-IgG antibodies and antinuclear antibodies in paired serum and synovial fluid samples. A comparison between juvenile and adult rheumatoid arthritis.

Paired samples of serum and synovial fluid (SF) from 13 patients with juvenile rheumatoid arthritis (JRA) and 10 patients with adult rheumatoid arthritis (RA) were examined regarding the level of immunoglobulins and the occurrence and titres of anti-IgG antibodies and antinuclear antibodies (ANA). The levels of immunoglobulins were lower in SF than in serum. In JRA the SF/serum ratio of IgG was equal to that of albumin, pointing to a local production of IgG. The SF/serum ratio of IgM was equal to that of alpha 2-macroglobulin. In JRA the SF/serum ratios of immunoglobulins tended to be lower than in RA, the difference being significant for IgM. IgD autoantibodies and IgA anti-IgG were not found in JRA. IgE autoantibodies occurred in some cases, but in RA in more than 60%. In JRA the SF titres of anti-IgG and ANA were most often lower than the serum titres. In RA the SF titres were often higher than the serum titres. In 9 of 10 paired SF samples from patients with RA the SF/serum ratios were mutually different with regard to one or several immunoglobulins. Evidence of synovial production of anti-IgG antibodies of classes other than IgG distinguished RA from JRA. Otherwise the differences were quantitative.

Adolescent↗