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Biomedical subjects

R J Levinsky

Publications and source records attributed to R J Levinsky.

At least 19 recordsLinked to original sources
PubMed1992

Superoxide production by normal and chronic granulomatous disease (CGD) patient-derived EBV-transformed B cell lines measured by chemiluminescence-based assays.

We have compared assays for products of the neutrophil respiratory burst in normal EBV-transformed B cell lines stimulated with agonists of protein kinase C. Those measuring O2- directly or its immediate product, H2O2, were successful. Of these, the most sensitive were the lucigenin- and luminol-based chemiluminescence assays for O2- and H2O2 respectively. Cell lines from CGD patients, with X-linked or autosomal recessive genetic defects in the neutrophil NADPH oxidase, did not respond in these assays, indicative of their inability to produce O2-. The defects in the lines studied encompass both proteins forming the cytochrome b-245 membrane component, and the 47 kDa cytosolic component of the NADPH oxidase. The possession of the disease associated phenotype by these cell lines provides evidence that in the normal situation both neutrophils and B cells produce O2- via the same system.

Acridines↗
PubMed1992

Immunodeficiency presenting as hypergammaglobulinaemia with IgG2 subclass deficiency.

Recurrent bacterial infections, lymphadenopathy, and failure to thrive are unlikely to be attributed to immune deficiency if they occur in the presence of hypergammaglobulinaemia, and other explanations will usually be sought. We describe eight patients who presented with all these features in infancy or early childhood. Deficiencies of immunoglobulin and antibody production were initially discounted, and the children were referred for investigation of possible lymphoma, autoimmune disease, or chronic viral infection. The patients were later referred to us for more detailed immunological investigation, which revealed low levels of IgG2 and poor specific antibody production to common pathogens. Treatment with intravenous immunoglobulin resulted in resolution of signs and symptoms in all patients. Thus we have shown that hypergammaglobulinaemia does not preclude the presence of immunoglobulin/antibody deficiency. We suggest that investigation of children with high levels of IgG and features of immunodeficiency should include IgG subclass analysis.

Adolescent↗
PubMed1992

Identification of CpG islands around the DXS178 locus in the region of the X-linked agammaglobulinaemia gene locus in Xq22.

The X-linked agammaglobulinaemia (XLA) gene locus has previously been mapped to Xq22. Genetic linkage analysis has shown tight linkage between the disease and the DXS178 locus and that DXS3 and DXS94 are the closet proximal and distal flanking markers, respectively, separated by a genetic distance of 10-12 cM. We attempted to construct a physical map of Xq22 using pulsed field gel electrophoresis (PFGE) and rare-cutting restriction enzymes in order to obtain a finite physical value for the distance between DXS3 and DXS94. However, these attempts were hampered by the large number of rare-cutting restriction enzyme sites around the DXS178 locus, indicative of the presence of CpG rich regions of DNA. We were able to construct a physical map of the sites close to DXS178 that suggests the presence of at least three, and perhaps as many as five, CpG islands. These are arranged on either side of DXS178, extending over about 550kb of genomic DNA. Each of these regions must be considered as being associated with a potential "candidate" gene sequence for the XLA gene and we have initiated a chromosome walk from DXS178 to the nearest of these islands.

Agammaglobulinemia↗
PubMed1992

Identical point mutation leading to low levels of mannose binding protein and poor C3b mediated opsonisation in Chinese and Caucasian populations.

A common opsonic defect occurring in 7% of the Caucasian population is associated with low serum levels of the lectin mannose binding protein (MBP). This study sought to determine whether the deficiency was also present in a Chinese population using sera obtained from 100 healthy Chinese children (age range 6 weeks-16 years). The distribution profiles of MBP levels and C3b/C3bi fragments binding to mannan coated plates were both bimodal and similar to the corresponding Caucasian profiles. Serum MBP levels were low in 9% of the Chinese children and all of these sera generated low levels of C3b/C3bi fragments. Overall there was a high significant correlation between MBP levels and C3b opsonin generation (r = 0.77; P less than 0.001). By analogy with similar findings in a Caucasian population we believe this correlation to be a reflection of antibody independent complement activation by MBP. In a pilot study of DNA obtained from three adult Chinese with low MBP levels the point mutation causing MBP deficiency in Caucasians was identified in all three cases.

Adolescent↗
PubMed1992

High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene.

We have previously identified, in three British families having an index child with frequent infections, a point mutation (GGC-->GAC) in codon 54 of exon 1 of the gene for the human lectin mannose binding protein (MBP). This was associated with low serum levels of this complement activating protein and would be anticipated to impair opsonization of mannose rich microorganisms. We now report a second point mutation (GGA-->GAA) in Gambians from West Africa, involving codon 57 of exon 1. By substituting carboxylic acids for axial glycines in the translated proteins both mutations would be expected to disrupt the secondary structure of the collagenous triple helix of the 96 kDa MBP subunits. In the Gambians the codon 57 mutation was studied by PCR, sequence analysis and restriction analysis and found to be remarkably common (frequency of the mutant gene 0.29 in adults and 0.23 in newborns) whereas the codon 54 mutation was very rare (frequency 0.003). However, the codon 54 mutation was frequent in both a British Caucasian and a Hong Kong Chinese population (frequency of the mutant gene 0.17 and 0.11 respectively). It was predicted that both homozygous and heterozygous individuals would have profoundly reduced serum levels of the protein and this was confirmed by immunoassay as was the reduced capacity of such sera to activate complement through the MBP initiated classical pathway. Our data indicate that the two mutations have arisen independently since the divergence of African and non African populations and both have attained high frequencies.

Adult↗
PubMed1992

Role of cell wall polysaccharide in the assessment of IgG antibodies to the capsular polysaccharides of Streptococcus pneumoniae in childhood.

The interference of antibodies to pneumococcal cell wall polysaccharide (CWPS) in the measurement of antibodies to capsular polysaccharides in children was assessed after vaccination with pneumococcal polysaccharide vaccine. ELISAs were developed to measure IgG subclasses specific for pneumococcal types 3, 6, 19, and 23 and CWPS. Analysis of antibody levels to all four capsular polysaccharides was affected by the presence of antibodies to CWPS, and their removal altered both anti-capsular polysaccharide antibody levels and the interpretation of responses to the vaccine. Thus, it is likely that CWPS contaminating pure capsular polysaccharide reagents used in most standard immunoassays is responsible for falsely elevated measurements of antibodies to capsular polysaccharide and the incorrect assessment of anti-pneumococcal antibody status in childhood.

Adolescent↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

Circulating soluble immume complexes in recurrent oral ulceration and Behçet's syndrome.

Circulating IgG immune complexes were assayed by means of agglutination inhibition of IgG-coated latex particles to human IgG by rabbit IgM antibodies. Sera from thirty patients with Behçet's syndrome, thirty patients with recurrent oral ulcers and thirty healthy control subjects were analysed. The results showed raised levels of immune complexes in 60% of patients with Behçet's syndrome and 40% of patients with recurrent oral ulcers. There were significant differences in the levels of immune complexes between the neuro-ocular and arthritic types of Behçet's syndrome as compared with the muco-cutaneous type of Behçet's syndrome or recurrent oral ulceration. A close association was found between the disease activity and the amount of immune complexes. These results suggest that immune complexes may play a part in the transition from the epithelial involvement of mucosa or cutaneous tissues to the neuro-ocular and arthritic types of Behçet's syndrome. Another factor in tissue distribution might be the size of immune complexes, as multi-focal involvement of tissues in the neuro-ocular type of Behçet's syndrome is associated with a broad range of immune complexes from 3 X 10(5) to 3 X 10(6) daltons.

Antigen-Antibody Complex↗