Biomedical subjects

D M Roberton

Publications and source records attributed to D M Roberton.

At least 55 records · Page 3Linked to original sources

PubMed1989

Antibodies to polyclonal IgA, IgA1, and IgA2 and isotype-specific immune complexes in IgA nephropathy.

The concentrations of serum IgG and IgM antibodies to polyclonal IgA (IgAp), IgA1, and IgA2 were determined by enzyme immunoassay in 31 patients with IgA nephropathy and 30 healthy controls. Patients with IgA nephropathy had significantly raised concentrations of serum IgA compared to controls (Mann-Whitney U test, P = 0.001) and increased concentrations of conglutinin-binding IgA immune complexes (P = 0.024). No differences in the median concentrations of IgG and IgM anti-IgA antibodies were found between the patients and the controls. In serum samples from healthy controls there was a significant positive correlation between IgM anti-IgAp and IgA immune complex concentrations (P = 0.05), which contrasted with the finding of an inverse correlation between IgM anti-IgAp and IgA immune complex concentrations in patients with IgA nephropathy (P less than 0.05). In addition, the concentrations of conglutinin binding IgM immune complexes in serum were found to correlate with the concentration of IgM anti-IgAp (0.010 less than P less than 0.025), IgM anti-IgA1, and IgM anti-IgA2 (P much less than 0.005 for both) in patients with IgA nephropathy but not in controls. IgM anti-IgA antibodies may be important in augmenting the clearance of IgA immune complexes from the serum of patients with IgA nephropathy.

Adolescent↗

PubMed1989

Comparison of concentration and avidity of specific antibodies to E. coli in breast milk and serum.

To investigate the relationship between mucosal and systemic immunity we analysed the specific anti-Escherichia coli antibody concentration and avidity of IgA in colostrum and IgG in paired blood samples from 47 mothers giving birth to premature neonates. The avidity of each sample, expressed as an avidity index, was determined using a novel enzyme immunoassay (EIA)-based procedure, while specific antibody determinations were performed by means of conventional sandwich EIA techniques. All subjects had detectable antibody to E. coli in serum and breast milk. The median avidity index for specific IgA antibody in breast milk (3.53 M NH4SCN, range 2.77-4.90) was significantly higher (P less than 0.0001) than that for specific IgG antibody in serum (median 2.03 M NH4SCN, range 1.15-3.65). Using Spearman correlation analysis, a weak but significant association was found between the avidity of colostral IgA antibody and the avidity of systemic IgG antibody to pooled E. coli polysaccharides (rs = 0.29, P = 0.02). There was also a weak correlation between the concentrations of specific serum IgG antibody and of specific colostral IgA antibody (rs = 0.36, P = 0.006). There was no correlation between the concentration of IgA anti-E. coli antibody in colostrum and the avidity of colostral IgA antibody (rs = 0.14, P less than 0.05). Similarly, there was no correlation between the concentration and the avidity of serum IgG anti-E. coli antibody (rs = 0.23, P less than 0.05). The findings of this study suggest independent regulation of concentration and avidity of specific IgA antibody in preterm breast milk. Similar results were seen for specific IgG antibody in serum. The correlations between systemic and mucosal antibody with respect to both concentration and avidity were significant, but are relatively weak and therefore suggest that there also may be independent factors which afford differential regulation of systemic and mucosal antibody responses.

Antibodies, Bacterial↗

PubMed1989

Enhanced IgG1 and IgG3 responses to pneumococcal polysaccharides in isolated IgA deficiency.

Serum IgG subclass-specific antibody concentrations to pneumococcal polysaccharides (PnPs) 1 and 14 were measured in 13 adult patients with isolated IgA deficiency and nine healthy adults immediately before and 4 weeks following immunization with polyvalent pneumococcal vaccine. Samples were analysed by enzyme immunoassay using pooled human serum as a reference preparation. A significant rise in median post-immunization antibody concentrations to PnPs14 was seen for all IgG subclasses, for IgA-deficient patients and for controls. For PnPs1, post-immunization IgG2 and IgG4 antibody concentrations rose significantly in the patient group, and IgG4 antibody concentrations rose significantly in the controls. The median IgG1 and IgG3 antibody concentrations to PnPs1 were significantly higher pre- and post-immunization in IgA-deficient individuals in comparison with controls, as were post-immunization IgG3 antibody concentrations to PnPs14. This enhancement of IgG1 and IgG3 antibody responses to pneumococcal polysaccharide antigens in IgA-deficient patients suggests an alteration in regulation of the normal switching processes in the generation of subclass and isotype diversity or could possibly be due to alteration in the affinity of subclass specific antibody.

Adult↗

PubMed1988

Anti-IgA antibodies in IgA-deficient children.

IgG and IgM isotype antibodies to polyclonal human IgA, myeloma IgA1, and myeloma IgA2 were estimated in 38 IgA-deficient children aged between 0.9 and 15 years. All children had IgM anti-IgA antibodies. IgG antibodies against either polyclonal IgA, IgA1, or IgA2 were present in 63% of the IgA-deficient children. IgG anti-IgA antibodies were detected against all three antigens in 8 of 11 severely IgA-deficient children and in 7 of 27 partially IgA-deficient children, but in only 1 of 23 healthy adult controls. The proportion of children with IgG anti-IgA antibodies was significantly greater in the severely IgA-deficient group in comparison with the partially IgA-deficient group and the adult controls (chi-square test, P less than 0.01 and P less than 0.005, respectively). There was a strong correlation within each IgG subclass between antibody responses toward each of the three IgA antigens. Twenty-four children were followed over a period ranging from 0.9 to 11 years (mean, 2.3 years). Three children who were initially IgG anti-IgA antibody negative became antibody positive and three who were antibody positive became antibody negative. Five children with severe IgA deficiency remained severely IgA deficient and IgG antibodies to IgA persisted in all five at follow-up. The presence of IgG anti-IgA antibodies did not influence the normalization of serum IgA at follow-up in 14 of 19 children who were initially partially IgA deficient.

Adolescent↗

PubMed1988

Avidity of IgA antibody to Escherichia coli polysaccharide and diphtheria toxin in breast milk from Swedish and Pakistani mothers.

The avidity of breast milk IgA antibody was studied with the aid of thiocyanate elution of antibody from solid-phase bound E.coli polysaccharides and diphtheria toxoid. The relative avidity index for each sample was determined by the molarity of thiocyanate required to elute 50% of the bound IgA antibody under conditions of antigen excess. Milk samples collected from Pakistani mothers during early lactation (2-4 weeks after delivery; n = 12) had a significantly lower median relative avidity index of IgA antibody to E.coli antigens than did early lactation samples from Swedish mothers (n = 11; avidity indices 1.78 M and 2.65 M; P less than 0.02). Samples collected from Pakistani mothers in mid-lactation showed a significant rise in the relative avidity index to a median of 2.50 M (P less than 0.01), with a subsequent fall in late lactation (28-36 weeks after delivery) to 1.75 M (P less than 0.01). Milk samples from Pakistani mothers in mid-lactation (n = 12) also had a lower median relative avidity index of IgA antibody to diphtheria toxoid than did samples from Swedish mothers (n = 14; avidity indices 2.35 M and 4.30 M; P less than 0.002). The lower avidity of breast milk IgA in Pakistani mothers in comparison with Swedish mothers may arise from differences in antigen exposure or nutritional status or could possibly be genetically determined.

Antibody Affinity↗

PubMed1988

Serum and salivary antibody responses to non-capsular Haemophilus influenzae antigens in children with meningitis and epiglottitis.

Serum IgG, IgA and IgM antibody and salivary IgA antibody concentrations to non-capsular Haemophilus influenzae antigens were measured in 13 children with H. influenzae type b meningitis and in 15 children with epiglottitis. Most had detectable serum IgG and IgM antibody at presentation but significantly fewer patients with meningitis had serum IgA antibody at presentation (P less than 0.05). Serum antibody concentrations had risen significantly by 3 weeks after presentation in patients with epiglottitis only. Convalescent serum IgG antibody concentrations against these antigens were higher in younger children with epiglottitis. Salivary IgA antibody to H. influenzae was detectable at presentation in all children with epiglottitis and in 12 of 13 with meningitis. Salivary antibody concentrations did not differ significantly between the two patient groups at presentation, although patients with meningitis had higher salivary IgA antibody concentrations than 10 children of similar age with bronchiolitis (P less than 0.02). There was no association between the presence of salivary antibody and low concentrations of convalescent serum antibody. The rise in convalescent serum antibody concentrations to non-capsular H. influenzae antigens only in children with epiglottitis is similar to findings for antibody to capsular polysaccharide. However, this rise was greater for IgG in younger patients, and the low titre of convalescent serum antibody in patients with meningitis was not associated with higher titres of IgA antibody in secretions as described by others for polysaccharide antibody. These findings suggest that the poor serum antibody response to these antigens in patients with meningitis is independent of age and is not due to mucosal induction of systemic tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗

PubMed1988

Use of methylprednisolone as prophylaxis for immediate adverse infusion reactions in hypogammaglobulinaemic patients receiving intravenous immunoglobulin: a controlled trial.

Ten children and young adults with humoral immunodeficiency disorders were enrolled in a blind crossover study of the effect of intravenous methylprednisolone in preventing immediate adverse infusion reactions to intravenous immunoglobulin. The patients selected had all experienced frequent adverse reactions previously. Each patient received two infusions of intravenous immunoglobulin at least 4 weeks apart. Infusions were of constant volume and rate for each patient. Intravenous methylprednisolone in a dose of 1 mg/kg bodyweight was given 20 min prior to one of the infusions only. A significant decrease in the severity of infusion-associated immediate adverse reactions was seen following the administration of methylprednisolone (P less than 0.01). Interruption of the infusion was necessary for only one patient when methylprednisolone prophylaxis was given, but temporary cessation of the infusion was required for eight of the 10 patients when methylprednisolone was not given (P less than 0.05).

Adolescent↗

PubMed1988

Human-isotype-specific enzyme immunoassay for antibodies to pneumococcal polysaccharides.

A simple enzyme immunoassay has been developed to allow the quantitation of the human response to immunization with pneumococcal polysaccharide. The assay uses the 14-valent vaccine (Pneumovax) as a convenient antigen to adsorb to the solid-phase microdilution plate wells and commercially available isotype-specific antibody conjugates. The results have been expressed as arbitrary pneumococcal polysaccharide antibody units by reading off a standard curve constructed by using heterogeneous pooled serum. All nonimmunized subjects tested had immunoglobulin G (IgG) antibodies present in serum. All six control subjects who were immunized with Pneumovax demonstrated an IgG response, and the majority responded with a rise in IgA- and IgM-specific antibody concentrations at a mean of 6 weeks postimmunization. Five out of six cord sera tested contained IgG antibodies only, which were present in concentrations similar to those seen in adults, whereas in 6- to 12-month-old infants only low levels of IgG and IgM and no IgA antibodies were detected. Serum taken from 10 hypogammaglobulinemic patients immediately prior to infusion of immunoglobulin showed low to negative IgG antibody concentrations, and no IgA or IgM antibody was present.

Adult↗

PubMed1988

Failure of intraventricular gammaglobulin and alpha interferon for persistent encephalitis in congenital hypogammaglobulinaemia.

A boy with congenital hypogammaglobulinaemia died at the age of 12 years after a viral meningoencephalitis of two and a half years duration due to an untypable picornavirus. He had received intravenous immunoglobulin every four weeks from the time of the start of immunoglobulin replacement treatment at the age of 3 years. The encephalitis did not respond to high dose intravenous gammaglobulin (2500 g during 22 months). The virus could not be isolated during the administration of intraventricular immunoglobulin (38.15 g) and intraventricular recombinant alpha interferon (121 X 10(6) units), but recurred rapidly each time intraventricular treatment was stopped. Further modes of treatment are still required for prevention and treatment of this disorder.

Agammaglobulinemia↗

PubMed1987

Estimating the relative avidity of mucosal IgA for antigen.

This report concerns the application of a method to estimate the relative avidity of mucosal IgA for casein and beta-lactoglobulin. The chaotropic ion, thiocyanate, was used to disrupt antigen-antibody binding in an enzyme immunoassay. The resultant proportional decrease in optical density of the enzyme immunoassay was directly related to the proportion of IgA eluted from the solid phase-bound antigen. The relative avidity was expressed as the molarity of KSCN resulting in a particular reduction in optical density. The measurement of avidity, the avidity index, was independent of the concentration of mucosal IgA. For anti-casein IgA the interassay coefficient of variation of the index was 14-18%, and the intra-assay coefficient of variation was 6%. For anti-beta-lactoglobulin IgA the interassay coefficient of variation was 10-13% and the intra-assay coefficient of variation was 6%. The method is simple and free of complicated calculations.

Antibody Affinity↗

PubMed1987

Purification of polymeric immunoglobulin from cell culture supernatants by affinity chromatography using secretory component.

Human secretory component bound covalently to Sepharose 4B has been used as an affinity adsorbent to isolate and purify polymeric immunoglobulin from cell culture supernatants. The method was used to isolate murine IgM isotype anti-trinitrophenol antibody and rat IgM isotype anti-lymphocyte antibody from hybridoma cell culture supernatants. Gel filtration of the eluted antibodies followed by enzyme immunoassay showed that all recovered IgM was of pentameric molecular size. Murine IgA isotype anti-dinitrophenol antibody and murine IgA anti-human rotavirus antibody were isolated from cell culture supernatants of a plasmacytoma and a hybridoma respectively. Most of the IgA recovered following affinity adsorption with secretory component was of greater molecular size than dimer. Murine IgG was not adsorbed by secretory component bound to Sepharose. Eluted antibody retained antigen binding activity. Affinity chromatography using human secretory component bound covalently to a solid phase provides an antigen-independent technique for purification of murine and rat IgA and IgM polymeric immunoglobulin from cell cultures.

Animals↗

PubMed1987

Decreased incidence of adverse infusion reactions in hypogammaglobulinemic children receiving low pH intravenous immunoglobulin.

Eighteen patients (ages eight months to 20 years) with disorders of immunoglobulin and antibody production received infusions of two preparations of intravenous immunoglobulin in a blind crossover trial. The incidence and severity of immediate adverse infusion reactions was significantly lower with low pH immunoglobulin; ten patients (56%) experiencing immediate reactions with the standard preparation and only one patient experiencing an immediate reaction with the low pH preparation (p less than 0.01). Infusion times were significantly less with the low pH preparation (p less than 0.02) and patient tolerance, determined by visual analogue scores, was significantly better than with the standard preparation (p less than 0.01). However, the incidence of delayed reactions (44%) was the same for both infusions.

Adolescent↗

PubMed1987

The long term treatment of childhood hypogammaglobulinaemia in Melbourne with intravenous gammaglobulin, 1972-1985.

Intravenous immunoglobulin has been used for hypogammaglobulinaemic conditions treated at the Royal Children's Hospital, Melbourne since 1972. Fifty-four children have been treated. Nineteen have been males with congenital hypogammaglobulinaemia (including 12 with sex-linked agammaglobulinaemia and 5 with hypogammaglobulinaemia with IgM); 8 have had common variable immunodeficiency, and 11 have had severe combined immune deficiency. Intravenous immunoglobulin has also been used for some patients with transient hypogammaglobulinaemia, isolated IgG deficiency, isolated IgA deficiency and isolated IgM deficiency. Infusions are given four weekly at a dose of 5-7.5 ml/kg of a 6% preparation (300-450 mg/kg). At diagnosis, a loading dose is given of 10-15 ml/kg (600-900 mg/kg). Previous studies have demonstrated a half-life of 25 days. The median preinfusion IgG concentration for the 22 children receiving monthly infusions currently is 68 IU/ml. Hospitalisation rates for infective illness have been reduced with the use of intravenous gammaglobulin. No patients are known to have developed hepatitis. Reactions to infusions are experienced by 60% of patients. These have not been reduced significantly by the addition of 10% maltose, but have been lessened considerably by using intravenous methylprednisolone (1 mg/kg) before the commencement of infusion.

Agammaglobulinemia↗

PubMed1986

Marrow function reconstitution by fraction 3 of Percoll-density-gradient-separated cells.

Eight children with advanced tumors or acute myeloid leukemia were treated either with very-high-dose multi-agent chemotherapy (4) or marrow ablative high-dose melphalan (4) followed by autologous marrow rescue, using only fraction 3 from a Percoll-discontinuous density gradient separation of bone marrow buffy coats. Each patient received less than 20% of the number of cells usually reinfused from the buffy coat. The yield of CFU-c in Percoll gradient 3 was similar to the yield obtained from whole buffy coats of bone marrow. Reconstitution of marrow function with a neutrophil count greater than 0.5 X 10(9)/L and platelet count greater than 50 X 10(9)/L occurred in 7 patients in a medium time of 15 and 16 days, respectively--a time comparable to that following infusion of whole buffy coat in 20 other patients. In one patient, hemopoietic recovery was considerably delayed, suggesting that fraction 3 from the Percoll gradient had been relatively ineffective in marrow reconstitution. We conclude that fraction 3 from marrow separated on Percoll gradients has the advantages of small volume and good recovery of marrow stem cells and can promptly reconstitute marrow function in the majority of children treated with very-high-dose chemotherapy or marrow ablative doses of melphalan.

Adolescent↗

PubMed1986

Immunological reconstitution in a patient with severe combined immune deficiency using non-sibling bone marrow depleted of T cells with HuLy-m1.

An infant with severe immune deficiency received bone marrow from an HLA-A, -B, -DR matched, mixed leucocyte reaction non-reactive first cousin. The donor marrow was fractionated on a discontinuous Percoll gradient and before infusion was treated with the anti-human T lymphocyte antibody, HuLy-m1, and rabbit serum as a source of complement. Methotrexate was given during the following two weeks. A rise in the peripheral blood lymphocyte count, indicating engraftment, occurred six weeks after transplantation. There was no clinical evidence of graft versus host disease (GVHD). Engraftment has been sustained for one year and the patient is in normal health and has normal in vitro immunological function. In vitro treatment of human marrow with HuLy-m1 allows stable engraftment and may be useful in attempting to diminish or prevent GVHD.

Animals↗

PubMed1986

A new type of transient diabetes mellitus of infancy?

Two male siblings with transient diabetes mellitus were of normal birth weight, were asymptomatic, and did not require treatment with insulin. This may be a previously undescribed disorder or part of the range of transient diabetes mellitus of infancy. Previously reported infants with transient diabetes mellitus of infancy have usually been small for gestational age and have presented with glycosuric dehydration, infections, or growth failure. Insulin concentrations after oral glucose challenge showed inadequate insulin secretion with respect to the degree of hyperglycaemia in these children. Autosomal dominant inheritance may occur in some families with this disorder, and parents of some affected children may also have had asymptomatic or unrecognised transient diabetes mellitus of infancy. Leucocyte histocompatibility antigen typing of this family did not show any association of specific antigens with transient diabetes mellitus of infancy in the affected children.

Blood Glucose↗

PubMed1986

Early induction of secretory immunity in infancy: specific antibody in neonatal breast milk.

Neonatal breast milk from 50 babies aged between 2 and 39 days was studied for the presence of antibody to the cows' milk protein beta lactoglobulin. Specific IgA antibody and specific secretory antibody to beta lactoglobulin were detectable towards the end of the second week of life in milk secreted by neonates fed cows' milk formula. Specific antibody concentrations were independent of total IgA concentrations. Babies receiving little or no cows' milk protein did not produce antibody in neonatal breast milk. Antigen specific mucosal immune responses develop in tissues distant from the site of primary mucosal exposure by the end of the second week of life in term human neonates, suggesting that prophylactic immunisation against enteric or other mucosal pathogens within a few days of birth may provide antibody responses in secretions, which may protect against mucosal infection.

Aging↗

PubMed1984

The use of discontinuous Percoll gradients to separate populations of cells from human bone marrow and peripheral blood.

Cells from human bone marrow samples were separated on discontinuous Percoll gradients and the effects of variations in osmolality were studied. Yield of committed progenitor cells as determined by CFU-c and BFU-E assays was improved when a gradient of discontinuous osmolality (360-320 mosM) was compared with gradients of uniform osmolality (320 mosM and 290 mosM). The CFU-c and BFU-E containing fraction recovered from this gradient also contained fewer T cells. When used for separation of peripheral blood samples, the same gradient yielded populations of mononuclear cells, neutrophils and platelets of more than 90% purity.

Adolescent↗