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Biomedical subjects

R J Levinsky

Publications and source records attributed to R J Levinsky.

At least 163 records · Page 9Linked to original sources

Long-term abnormalities in T and B lymphocyte function in children following treatment for acute lymphoblastic leukaemia.

T and B lymphocyte function as assessed by pokeweed mitogen stimulation and concanavalin A suppression was studied in 40 children with acute lymphoblastic leukaemia who were in remission and off all treatment. Both plasma cell and immunoglobulin production was reduced in off-treatment patients, particularly in those who had received cyclophosphamide as part of their treatment. The ability to suppress immunoglobulin production was also significantly reduced in these patients. These abnormalities were long-standing and were apparent up to 5 years after stopping treatment with no indication of a return to normality. No clinical correlations have been observed.

Adolescent↗

Differences in specific antibody responses of human tonsillar cells to an oral and a parenteral antigen.

Tonsillar lymphocytes stimulated in vitro with either beta-lactoglobulin or with tetanus toxoid were shown to produce specific antibodies by a direct plaque assay and by radioimmunoprecipitation of the culture supernatants. There was a sixfold increase in the number of IgA-secreting cells in response to beta-lactoglobulin; no such effect was seen in response to tetanus toxoid, where a fivefold rise in IgG-secreting cells occurred. These differences in antibody response are probably due to the route of initial antigen presentation. Those antigens priming the mucosa-associated lymphoid system stimulate mainly IgA-producing cells, in contrast to parenteral antigens, which elicit a predominantly IgM and IgG response.

Administration, Oral↗

A polymorph bactericidal defect and a lupus-like syndrome.

We describe a child with primary defect of polymorph bacterial killing associated with systemic lungs erythematosus. We suggest that her autoimmune disease results from chronic bacterial antigen stimulation and propose a hypothetical model linking immunodeficiency with autoimmunity.

Blood Bactericidal Activity↗

Specific antigen exclusion and non-specific facilitation of antigen entry across the gut in rats allergic to food proteins.

The intestinal absorption of ovalbumin and beta-lactoglobulin was measured in Hooded Lister rats which had previously been made allergic to ovalbumin, and in unimmunized controls. The antigens were introduced both together and separately into closed intestinal loops. Absorption of free ovalbumin, but not beta-lactoglobulin, was reduced in rats with anti-ovalbumin antibody, demonstrating antigen-specific immune exclusion despite the presence of reaginic antibody. In contrast, the absorption of beta-lactoglobulin was enhanced by the presence of ovalbumin in rats with IgE anti-ovalbumin, but not in unimmunized controls. These results suggest that macromolecular absorption may be increased in an antigen non-specific way in food allergy.

Animals↗

Detection of specific antigen within circulating immune complexes: validation of the assay and its application to food antigen-antibody complexes formed in healthy and food-allergic subjects.

A simple two-step method for the detection of specific antigen within immune complexes is described. The immune complexes are precipitated from serum by polyethylene glycol, dissociated by incubation in acid pH buffer and adsorbed onto the surface of polystyrene tubes. The antigen is detected by the binding of a radiolabelled affinity-purified specific antibody. The assay can detect the antigen within both antigen- and antibody-excess immune complexes of any immunoglobulin class, and can also allow semiquantitative comparison of different samples. Immune complexes containing food protein antigens after eating have been found in the serum of both normal subjects and atopic patients; the latter group showed higher mean levels of antigen-specific immune complexes. The method can be adopted for large-scale screening of clinical samples for suspected antigens if suitable antisera are available.

Adult↗

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↗

Solid phase radioimmunoassay for detection of circulating food protein antigens in human serum.

A two site solid phase radioimmunoassay for detection of common food antigens is described. Bovine serum albumin, beta-lactoglobulin and ovalbumin can be detected in normal human serum at levels ranging from 0.1 to > 1000 ng/ml; sensitivity is not impaired by the presence of low levels of antibodies. Thirty min to 3 h after oral intake of milk, beta-lactoglobulin could be detected in the sera of 3 normal individuals, at a concentration of 0.1-3 ng/ml. This assay should prove useful in assessing the importance of macromolecular absorption in food allergy and in other gastrointestinal diseases.

Adult↗

Circulating immune complexes in onchocerciasis.

Circulating immune complexes were detected in sera of patients with both localized and generalized onchocerciasis by a 125I-Clq binding assay but not by the IgG latex agglutination inhibition method. Gel filtration of sera demonstrated high molecular weight Clq-reactive material(greater than 2 x 10(6) Daltons) which contained IgM but no IgG. Antibody titres to Onchocerca volvulus antigen were higher in patients with generalized disease than in those with the localized form. The lack of correlation between antibody titres and levels of immune complexes suggests that these immune complexes contain antigens other than those derived exclusively from the parasite. Although few of the symptoms of this disease are likely to be due to deposition of circulating immune complexes, the depression of delayed hypersensitivity reactions to the parasite found in patients with generalized onchocerciasis may be due to IgM immune complexes exerting an immuno-regulatory role on T cell function.

Adolescent↗

IgA immune complexes in Henoch-Schönlein purpura.

Raised levels of IgA immune complexes were found in 13 of 18 children with Henoch-Schönlein purpura irrespective of whether they developed nephritis or not. In contrast, only those children who developed nephritis had raised levels of IgG immune complexes as well. In 2 children with nephritis, two discrete peaks of IgA complexes were found, corresponding to 4 x 10(5) to 8 x 10(5) and 2.5 x 10(6) to 4 x 10(6) daltons. IgG complexes were found only in the larger-molecular-weight peak. Such differences in immune complexes may underlie the different manifestations of this disease.

Adolescent↗

Immune complexes containing food proteins in normal and atopic subjects after oral challenge and effect of sodium cromoglycate on antigen absorption.

After ingestion of food, immune complexes containing food proteins as antigens were demonstrated in the serum of normal and atopic subjects. In the atopic patients challenged with the food to which they were sensitive, abnormal levels were detected. The same atopic patients pretreated with oral sodium cromoglycate had less antigen entry, diminished immune-complex formation, and no atopic symptoms. Tests for antigen entry and immune-complex formation after oral challenge may permit objective assessment of food allergy and may show whether drugs such as oral sodium cromoglycate are likely to benefit individual patients.

Absorption↗

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 immune complexes in pre-eclampsia.

Sixteen patients with severe pre-eclampsia had more IgG-containing and C1q-binding circulating soluble immune complexes than did 16 matched women with normal pregnancies. The clinical features of preeclampsia may be explained by damage due to such complexes, although raised complex levels were also present in a few women with normal pregnancies. As immune complexes are so heterogenous in terms of the type of antigen, class and subclass of immunoglobulin, size, and complement-binding capacity, further investigations are needed to determine their role in normal and pre-eclamptic pregnancies.

Antigen-Antibody Complex↗

Circulating immune complexes in steroid-responsive nephrotic syndrome.

We analyzed serums from 39 children with steroid-responsive nephrotic syndrome for the presence of circulating soluble immune complexes. Seventeen of 18 children in relapse had raised levels of IgG complexes: median titers were significantly higher in these patients than in control children (P less than 0.001) or in nephrotic children in sustained remission (P less than 0.001). Seven of nine children followed sequentially had raised complex levels in early remission but became normal after six weeks in remission. In contrast to patients with systemic lupus erythematosus these IgG complexes were not able to bind C1q. Serums from five patients in relapse contained complexes intermediate in size (2 to 2.5 X 10(6) daltons) as compared to those seen in systemic lupus erythematosus, and four of the five had small complexes as well (3 to 5 X 10(5) daltons). These findings suggest that immune complexes may have a pathologic role in steroid-responsive nephrotic syndrome, but the mechanism by which proteinuria is effected remains unclear.

Adolescent↗

A rapid objective method for measuring the yeast opsonisation activity of serum.

A simple, objective semi-quantitative assay for yeast opsonisation by normal polymorphs has been developed. This depends on electronically counting the number of free unphagocytosed yeast particles on a Coulter counter. The method has been compared with the widely used microscope technique and shows excellent correlation. The sera of 112 unselected school-children gave a distribution curve consistent with 2 peaks; 7 gave values less than 2 S.D.s below the mean confirming the high incidence of this immunodeficiency.

Child↗