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Biomedical subjects

O Wager

Publications and source records attributed to O Wager.

At least 37 records · Page 2Linked to original sources

Evaluation of six tests for circulating IgG complexes with special reference to IgM rheumatoid factors: analysis of systemic lupus erythematosus and rheumatoid arthritis series.

Six tests for circulating immune complexes (CIC) developed in four laboratories and representing four main principles [affinity of human platelets, Clq, of RF for aggregated IgG, and of conglutinin (Kg) for complex-bound C3] were evaluated on series of SLE and definite RA. All tests detected human model complexes in the presence of NHS and discriminated the patient series from the blood donor series, most powerful being the PIPA (platelet test). The high correlation between the RF-binding inhibition tests (RFbI) and the RF-latex test suggested interference due to intrinsic RFs. This received further support from experimental analyses in which RA sera mixed with varying doses of heat-aggregated IgG were assayed by the pRFbI test.

Antigen-Antibody Complex↗

Effects of immune complexes on plasma triglycerides in rabbits.

The effect of immune complexes on plasma lipids, especially triglycerides (TG) was studied in rabbits. After a single intravenous dose of bovine serum albumin (BSA), serological aberrations suggestive of immune complexes appeared around the 14th day. Changes in the plasma TG or cholesterol values were not observed within a follow-up period of 4 weeks. However, reimmunization with a second dose of BSA 2 months later led to a significant decrease in plasma TG (P less than 0.01). In fat tolerance tests TG emulsion was given intravenously to rabbits immunized 14 days earlier with BSA. The elimination curve of exogenous TG (followed for 100 men) was in its first phase exponential and in it second phase linear in all experimental groups. The significance of the second phase, however, has to be interpreted with some caution because of the possible recirculation of TG into the blood stream. In the rabbits immunized with one dose of BSA the fractional removal rate of TG did not differ from that of the controls. However, in the rabbits reimmunized with a second dose of BSA 2 months later the fractional removal rate of TG was greater than in the controls (P less than 0.01). It was concluded that immune complex lesions under certain circumstances may affect the TG metabolism. The mechanism concerned may be increased permeability of the injured vascular endothelial cells, possibly through the increased release of lipoprotein lipase (LPL).

Animals↗

Rheumatoid factor in acute viral infections: interference with determination of IgM, IgG, and IgA antibodies in an enzyme immunoassay.

IgM rheumatoid factor (RF), an autoantibody to the Fc fragment of IgG, was determined by solid-phase enzyme immunoassay (EIA). RF levels were significantly higher in patients with rubella virus infection than in patients with infections due to influenza virus, cytomegalovirus, respiratory syncytial virus, parainfluenza virus, adenovirus, mumps virus, or herpes simplex virus. To evaluate the role of RF in EIA determinations of viral antibodies, IgM RF from IgM-IgG cryoglobulin or control IgM was added to patient sera before assay for viral antibodies. IgM RF inhibited virus-specific IgG and IgA reactions and gave nonspecific IgM reactions in EIA for antibodies to rubella and influenza viruses, but had little or no effect on antibodies to cytomegalovirus. The minimal effective amounts of RF were 100-500 ng/ml for inhibition of IgG, 300-1,000 ng/ml for IgA, and 25-500 ng/ml for IgM. The control IgM preparation gave no such effects. These studies reinforce the need to eliminate RF interference in solid-phase EIA.

Acute Disease↗

Circulating immune complexes in sarcoidosis.

Circulating immune complexes (CIC) were detected in 100 out of 112 sera from 33 sarcoidosis patients. Five tests were used representing three different basic principles. All patients had detectable CIC at some stage of their disease. The three platelet tests detecting IgG complexes exhibited the highest positive titres in the acute cases. The ClqB-ELISA test, which detects complement fixing IgG complexes, was the test most frequently positive in the chronic cases. The presence of extra-pulmonary lesions or corticosteroid therapy did not influence the appearance or disappearance of CIC. No positive correlation was found between CIC and elevated levels of serum angiotensin-converting enzyme (ACE) and/or serum lysozyme (LZM). The evaluation of CIC in sarcoidosis requires a battery of different tests carried out at regular intervals during the follow up.

Antigen-Antibody Complex↗

Autoimmune haemolytic anaemia and pulmonary vasculitis associated with circulating immune complexes.

A patient with autoimmune haemolytic anaemia and pulmonary vasculitis is described. Circulating immune complexes (CICs) were detected in both light and heavy fractions of the patient's serum by four CIC-tests. Antinuclear antibodies and hypocomplementaemia were also found. Immunosuppressive treatment reversed both the immune haemolysis and the pulmonary reaction. we suggest that the syndrome of our patients represents an unusual localized variety of SLE.

Anemia, Hemolytic, Autoimmune↗

Glomerular electron-dense deposits and circulating immune complexes in patients with malignant tumours.

39 patients with malignant neoplasms were studied for the presence of paraneoplastic glomerular disease. The nephrotic syndrome was found in none of the patients. From 24 patients an adequate renal biopsy specimen was available for examination by electron microscopy. Glomerular electron-dense deposits were found in the biopsies of 11 patients, and in four of them the deposits were subepithelial. Circulating soluble immune complexes were detected in the sera of 14 patients. Deposits and circulating immune complexes occurred simultaneously with a highly significant correlation. Cell-mediated immunity was studied using skin tests to tuberculin and dinitrochlorobenzene (DNCB). Negative tests were seen mainly in patients with circulating immune complexes and/or glomerular deposits. Median survival time in patients with deposits or circulating complexes tended to be shorter than in those without.

Aged↗

Heating at 56 degrees C does not eliminate immune complex-bound Clq.

The effect of heating at 56 degrees C on free and complex-bound Clq was studied by radioisotope and sucrose gradient centrifugation techniques. The ability of soluble complexes of egg albumin, rabbit anti-egg albumin, and human Clq to bind extrinsic iodinated Clq did not increase following heating at 56 degrees C. The results of this study did not support the postulated release of complex-bound Clq on heating at 56 degrees C. They also showed that free Clq was more heat-labile than Clq in the Clqrs state. The importance of elimination or monitoring of intrinsic Clq in Clq assays for circulating immune complexes is stressed.

Animals↗

Use of ELISA for measuring immunoconglutinins.

An enzyme-linked immunosorbent assay (ELISA) for detection of immunoconglutinins (IKs) has been developed. IKs are allowed to bind to solid-phase C3 and are then assayed using alkaline phosphatase coupled to anti-IgG or anti-IgM. IK activity was detected in some patients' sera up to 50,000-fold dilution. Significant correlation (r = 0.65) was obtained between the levels of IgM-IKs measured by ELISA and by conventional hemagglutination assay, IgG-IKs and hemagglutination titers did not correlate (r = -0.15).

Alkaline Phosphatase↗

IgG autoantibody to human serum albumin studied by the ELISA-technique.

ELISA was applied for analysis of the HSA-human IgG autoantibody system responsible for the immunoelectrophoretic 'Tailing Albumin' (TA) phenomenon induced in most of the TA patients by prolonged nitrofurantoin therapy. Both hyperimmune porcine anti-HSA and autoimmune human anti-HSA antibodies of the IgG class were detectable by ELISA. The presence of autologous or added HSA had some inhibitory effect upon the detectability of the anti-HSA antibodies. Partial elimination of the autologous HSA by sucrose gradient ultracentrifugation or salt precipitation increased or unmasked the anti-HSA activity of some TA sera. The sensitivity of the ELISA as detector of the anti-HSA autoantibodies of whole human sera was roughly equal to that of the immunoelectrophoretic TA phenomenon. The analogy of the anti-HSA autoantibodies and the rheumatoid factors and the theoretical interest of both of them is stressed.

Antigen-Antibody Complex↗

Binding affinity of human autoantibodies: studies of cryoglobulin IgM rheumatoid factors and IgG autoantibodies to albumin.

The binding affinity of cryoglobulin IgM rheumatoid factors (RF) for human IgG and of human IgG anti-albumin autoantibodies for HSA was measured by the molecular sieving technique. The binding affinities of the two autoantibodies were consistently low (10(4)-10(5) 1/M) as compared to the affinities of corresponding hyperimmune animal antibodies (10(6)-10(8) 1/M). The findings were discussed in relation to theories on human autoimmunity. The existence of strict autotolerance at the T cell level and of autoreactivity at the low affinity B cell level was considered to be best compatible with the findings of this study and with the major known facts of autoimmunity.

Antibodies↗

Lack of measurable complement fixing antibodies against viral antigens.

A serological and clinical study was performed to find the common features of 130 patients without antibodies against 11 or more different antigens in the complement fixation (CF) test. These patients (=1.6%) were discovered during hte screening of 8,021 adult patients. Rheumatoid factor(s) (RF) were found in the sera of 113 of the patients. In the remaining 17 patients no common serological or clinical markers were found. Myeloma M-components were found in three cases. The lack of measurable CF antibodies in RF positive cases was apparently due to the inhibitory effect of RF(s) in the CF test. This was indicated by a positive reaction in CF after centrifugal separation of IgM and IgG fractions and also by the detection of antibodies using immunodiffusion method. Possible immune complexes were sought using the platelet aggregation test, which was positive for the sera of 47 (=37%) of the patients. The clinical diagnosis of the 130 CF-nonreactors was rheumatoid arthritis (RA) (ARA criteria) in 23 cases and pulmonary diseases in 65 cases. In a comparison group of equal size there were only 3 RA patients and 15 with pulmonary disease. RA was thus found in 20% of the RF positive CF-nonreacting patients. In the comparison group of 52 RA patients 8 CF-nonreactors were found (=15%). This suggests that the effect of RF(s) from RA patients in CF reaction varies greatly.

Adult↗

Immunoelectrophoretic 'tailing' of albumin line due to albumin-IgG antibody complexes: a side effect of nitrofurantoin treatment?

The immunochemical analysis of sera of 10 patients in which immunoelectrophoresis showed a cathodic, elongated, 'tailing' albumin (TA) line is described. Eight of the 10 patients had been treated with nitrofurantoin, and withdrawal of the drug was followed by disappearance of the phenomenon in 5 cases. Most of the patients had polyclonally elevated IgG and IgA levels and a decreased albumin level; IgM; C3, C4, and C1-INH were normal. Antinuclear activity of IgG type was demonstrated in the sera of 9 patients. The TA phenomenon was due to noncovalently bound complexes between IgG and albumin. The combining sites of the IgG molecules were in the Fab fragment. The antibody-like activity of the IgG was directed towards autologous albumin. The anti-albumin activity remained unchanged after absorption of the antinuclear activity. The nitrofurantoin-induced albumin-anti-albumin system may prove useful as a human model of autoimmune response of known aetiology.

Aged↗

Blocking effect of rheumatoid factor on the in vitro cytotoxicity of lymphoid cells from carcinoma patients.

Human cryo-IgM rheumatoid factor (RF) preparations blocked the tumor-specific in vitro cytotoxicity of ovarian or bladder carcinoma patients' lymphoid cells in microcytotoxicity assays. The effect was mediated by pretreatment of the effector cells. Cryo-IgM RF free of detectable IgG blocked in a dilution-dependent manner, and immunosorbent purification of contaminating IgG from another preparation did not abrogate the blocking effect. Control IgM preparations lacking RF activity did not block the cytotoxicity, and normal human serum preincubation of the RF preparations rendered them inactive, indicating that the blocking effect was due to the anti-IgG activity of the RF.

Cryoglobulins↗