Analysis of antigens in the circulating immune complexes of patients with Coxsackie infections.
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Antigen-Antibody Complex↗
Biomedical subjects
J F Mowbray
Publications and source records attributed to J F Mowbray.
Desquamative interstitial pneumonia and antigen-antibody complexes in two infants with congenital rubella.
Desquamative interstitial pneumonia was observed in two infants with the late-onset congenital rubella syndrome. In both infants this unusual lung disease was associated with circulating immunoglobulin M complexes and interstitial pulmonary deposits of IgM by immunofluorescence. Both infants had IgG deficiency. The first child recovered with a reduction in IgM complex levels and synthesis of rubella-specific IgG. The second infant died during the acute phase of his illness at which time there were high serum concentrations of IgM complexes and slightly increased levels of IgG complexes. Delayed maturation of the immune response in congenital rubella may predispose to persistent antigenemia and pulmonary deposition of rubella antigen-containing IgM complexes resulting in an acute form of interstitial pneumonia.
Antigen-Antibody Complex↗
Linear IgA disease in adults.
A multi-centre study is described in which thirty-five adult patients with papillary IgA dermatitis herpetiformis (DH) were compared with forty-two patients with linear IgA deposits, of whom thirty-four had homogeneous-linear (HL) and eight had granular-linear (GL) IgA deposits. The three groups were similar with regard to age of onset, presence of circulating immune complexes and auto-antibodies, incidence of spontaneous remission, histology of lesional skin and response to dapsone. There was a female predominance in the HL group in contrast to the male predominance in the other two. It was not possible to diagnose the HL group clinically. Some patients had a rash typical of DH whilst others resembled pemphigoid. In the majority, however, no specific diagnosis could be made with confidence. The GL group clinically resembled the DH group. The incidence of positive potassium iodide patch tests was greater in the DH group than in the other two. An associated enteropathy was found in 24% of patients in the HL group, 30% of patients in the GL group and 85% of patients in the DH group. Fifty-six percent of HL patients had HLA-B8 compared with 50% in the GL group and 88% in the DH group. Patients with linear IgA deposits may not be a uniform group, but until they can be divided into specific subgroups (e.g. by ultrastructural localization of the deposit or by response to a gluten-free diet) we propose that the term adult linear IgA diseases should be used to distinguish these patients from those with papillary IgA deposits.
Adolescent↗
HLA dependence of sensitivity to nickel and chromium.
A group of patients with cutaneous sensitivity was compared with another group with cement dermatitis who showed sensitivity to chromate. HLA typing for A and B locus antigens demonstrated a 29% incidence of B21 in the nickel sensitive group (control population 4.9%) and the antigen was not found in 16 patients with chromium sensitivity. It is suggested that this may represent a hapten specific HLA dependent immune response in man.
Chromium↗
Circulating immune complexes in tuberculosis.
Using a polyethylene glycol precipitation method, immune complexes were detected in 56% of patients with active tuberculosis. After antituberculous treatment, 29% remained positive for immune complexes, a frequency similar to that in a group of racially matched clinic controls (35%). In a study of 17 patients whose immune complex levels were determined soon after diagnosis and again when the therapy had ceased, there was a significant decrease in complexed IgM and Clq. Sequential studies of immune complex levels in tuberculosis merit further investigation, their persistence may indicate the continued presence of antigens, and their disappearance from the circulation may be a guide to successful treatment.
Adolescent↗
Precipitating antibodies to factor VIII/von Willebrand factor in von Willebrand's disease: effects on replacement therapy.
Precipitating antibodies to factor VII/von Willebrand factor can develop in patients with severe homozygous-like von Willebrand's disease following multiple transfusions with blood derivatives. This study of 4 patients treated with cryoprecipitate for 13 different bleeding episodes demonstrates that the occurrence of such antibodies interferes with the management of the disease. The control of mucosal bleeding was poor, whereas more favorable responses were obtained in soft-tissue hemorrhages. These findings probably relate to failure of replacement therapy to shorten the prolonged bleeding time. Immediately after treatment, measurement of plasma factor VIII/von Willebrand factor-related antigen and ristocetin cofactor showed either no increase, or very low values, depending on the pre-infusion antibody titer. Levels of the factor VIII/von Willebrand factor-related procoagulant activity in the circulation were also lower than predicted and usually there was no evidence of the delayed and sustained rise typically observed in uncomplicated von Willebrand's disease. An anamnestic rise in antibody titer appeared 6-15 days after treatment and showed no obvious relationship with the amount of cryoprecipitate infused. Replacement therapy invariably caused severe side effects during, or immediately after, concentrate infusion. The results of in vitro studies support the view that these reactions were due to the appearance of circulating immune complexes.
Antibodies↗
Polymorphonuclear neutrophil iodination response as an estimate of defective yeast opsonization.
Polymorphonuclear neutrophil iodide uptake can be used as a measure of yeast opsonization and optimal assay conditions are described for the identification of sera defective in this function. The use of standard normal and defective sera permits correction of inter-assay variations resulting from the use of different cell donors. The iodination assay correlated well (r = 0.74, P less than 0.001) with a direct assay of yeast opsonization when both were used to measure this function in a panel of 72 sera. Differences in results between the two assay systems for some sera may be explained by a requirement for two different surface-associated opsonic molecules in the initiation of neutrophil metabolic activity.
Adult↗
A study of C3b deposition on yeast surfaces by sera of known opsonic potential.
C3c fragments released by the actin of trypsin from C3b molecules bound to zymosan may be readily quantitated by conventional gel techniques to give a measurement of the efficiency of C3b opsonization. Using this approach, the rate of deposition of C3b molecules was found to be very rapid in sera known to opsonize yeast normally. In contrast, sera defective in yeast opsonization deposited C3b much more slowly. The C3b elution technique was found to correlate well with both a direct phagocytosis assay using baker's yeast (r = 0.87, P less than 0.001) and a recently described neutrophil iodide uptake assay (r = 0.88, P less than 0.001).
Adult↗
Different cross-reacting circulating immune complexes in Behçet's syndrome and recurrent oral ulcers.
Circulating immune complexes were isolated by 2% polyethylene glycol precipitation from the sera of 15 out of 37 patients with Behçet's syndrome and 11 out of 23 patients with recurrent oral ulcers. The antigenic cross-reactions of the polyethylene glycol precipitates were studied by coating a plastic tube with one complex and adding another 125I-labeled complex in dissociating (acid) conditions. On neutralization, partial reassembly occurred with the complex coating the tube wall, thus indicating cross-reaction with it. In the first 30 complexes studied, the cross-reactions obtained were sorted by computer program into two mutually exclusive subsets of reactions. Two similar homologous subsets of reactions were found in the second group of 29 patients: in total, nine out of 16 ocular, four out of six herpetiform circulating immune complexes in one subset, and four out of seven neurological in the other. A wider pattern of reaction could be detected in addition, which induced most of the Behçet's syndrome and recurrent oral ulcers. Immune complexes from control sera did not cross-react. An exogenous agent could account for the circulating immune complexes' cross-reactions for the group as a whole, and two antigenic determinants of that agent or antigens from different damaged tissues explain the subsets.
Antigen-Antibody Complex↗
Significance of haematuria in hypertensive patients.
Of 409 patients attending a clinic for control of hypertension, 74 (18%) were found to have haematuria, and all those with haematuria had significant renal impairment. The association of raised serum IgA levels and HLA BW35 in these patients suggests that some have the adult form of the IgA/C3 disease described in children.
Adult↗
The atopic syndrome: in vitro immunological characteristics of clinically defined subgroups of atopic subjects.
Total IgE, selected specific IgE antibody levels, C2 and yeast opsonization were measured in four clinically defined subgroups of atopic patients who had previously been HLA-typed. Each group was characterized by a distinctive mean total IgE level and profile of specific IgE responses. All groups gave comparable levels of IgE antibodies to Timothy grass pollen but in patients initially presenting with infantile eczema and who subsequently developed asthma and/or hay fever, IgE antibodies to bovine milk proteins, egg ovalbumin and cat dander were frequently observed whereas in patients initially presenting with hay fever later in life these antibodies were usually absent. Computer assisted analysis failed to show any association between IgE antibody responses and (a) the HLA phenotypes A1,B8 and A3,B7 (b) C2 levels and (c) the yeast opsonization index.
Adult↗
Nature of circulating immune complexes in infective endocarditis.
Two percent polyethylene glycol (PEG) precipitation was found to be a useful method for detecting circulating immune complexes (CIC) and could be used diagnostically to implicate infective endocarditis. Complexes consisting of a least Clq, IgG, and IgA were typically detected in sera from patients with infective endocarditis. Serial studies showed that CIC detection and measurement could be used to monitor clinical progress. Successful clinical improvement was reflected by decreasing CIC levels and the disappearance of rheumatoid factor, and, where increasing amounts of CIC were found, this may indicate situations where treatment was insufficient or inappropriate. There was specific free antibody demonstrable in the serum of six out of nine patients against their own infecting organisms, but attempts to identify the specificity of the complexed antibody as being directed against these organisms or their extracellular products failed. We could not detect any radioactive precipitin arcs, indicative of the free antibody also being in the complex, between the F(ab')2 preparation from the complex and the electrophoresed bacterial antigens in a radio-immunoelectrophoresis system. Eleven out of 13 sera that contained Clq, IgG, and IgA in their complexes also contained rheumatoid factor. Immunisation against the patient's own persisting CIC may explain this phenomenon.
Adult↗
Defective yeast opsonisation of serum in sarcoidosis.
We have studied the opsonising ability of the sera of 49 patients with sarcoidosis. The serum of 11 (22%) patients was defective in this ability, whereas only two (4%) of 46 clinic control subjects and three (7%) of 43 laboratory control subjects showed this defect. The difference between the prevalence of the defect in sarcoidosis and the control groups was statistically significant (p less than 0.01). Although the patients with sarcoidosis who had this defect tended to have pulmonary infiltration, this relationship was not statistically significant. Similarly, there was no correlation between the activity of sarcoidosis and this defect, although there was a significant (p less than 0.05) relationship between the opsonising defect and the persistence of circulating immune complexes. Serum opsonisation is a genetically linked host defense mechanism. Our findings suggest that the presence of this serum defect may render a person more susceptible to sarcoidosis.
Adolescent↗
Circulating immune complexes in sarcoidosis.
The sera of 50 patients with sarcoidosis were tested for the presence of circulating immune complexes using polyethylene glycol precipitation, followed by single radial immuno diffusion for the amounts of Clg, IgG, IgM, and double diffusion for the presence of IgA. Complexes were detected in 29 (58%) patients. No correlation could be found between the presence of these complexes and the length of history stage, or activity of disease, nor to steroid therapy. Rheumatoid factor was detected in 14 patients (28%), 13 of whom had circulating immune complexes, and 12 of whom had active disease. Total serum C3, CH50, and Clq were normal, as were immunoglobulin levels. In patients with extrathoracic sarcoidosis, especially skin or joint involvement, complexes were commonly found. The aetiological significance of these complexes remains uncertain.
Adolescent↗
Defective yeast opsonisation of serum in tuberculosis.
We have studied the opsonising ability of the sera of 92 patients with tuberculosis. Fourteen per cent of these patients showed defective opsonising ability compared with 4% in a clinic control group. This increased frequency in TB was accounted for by the greatly increased proportion with defects found in patients with intrathoracic TB (21%). We may have identified a section of the population with a specific genetically linked abnormality of a host defence mechanism which renders them more susceptible to intrathoracic TB. Further population studies are required.
Adolescent↗
Circulating immune complexes containing anti-VIII antibodies in multi-transfused patients with haemophilia A.
Evidence for the presence of circulating immune complexes was found in thirty-four out of fifty-five samples from forty-seven patients with haemophilia A. In eleven patients the complexes, precipitated from the blood with polyethylene glycol, were digested with pepsin. The F(ab')2 antibody was tested, and found to have neutralizing activity against coagulant Factor VIII in two patients. In one of these no free antibody had ever been found in the plasma, while in the other the antibody was concentrated tenfold in the complex. In two other samples free without complexed antibody was found. In comparison, IgG-containing complexes were found in nine out of nineteen patients with von Willebrand's disease and no complexes were found in the sera from twelve multi-transfused thalassaemics. PEG precipitation is a useful technique for the preparation of concentrated immune complexes for further study such as antigen identification.
Adolescent↗
Antigen-antibody complexes in the serum of patients with juvenile chronic arthritis.
IgG-containing antigen-antibody complexes were detected in the sera of all of 7 patients with the systemic form of juvenile chronic arthritis, usually at high levels. Only 9 of 25 patients with the polyarticular form had such complexes, usually at low levels. Three patients had low levels of serum IgA which were probably drug induced; the one patient with low C2 and the 3 with low yeast opsonisation were probably not more than to be expected in a random population.
Adolescent↗
Circulating and deposited immune complexes in renal disease and their clinical correlation.
In 48 patients undergoing renal biopsy there was a strong correlation (chi 2 11.45 (P less than 0.01)) between the demonstration of circulating and deposited immune complexes. Serial studies of circulating immune complex levels have shown fluctuations which only sometimes appear to coincide with clinical changes in individual patients.
Antigen-Antibody Complex↗