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Biomedical subjects

F Shakib

Publications and source records attributed to F Shakib.

At least 19 recordsLinked to original sources

The recognition of a recombinant human Fc epsilon fragment by the subclasses of IgG autoanti-IgE: disproportional subclasses distribution of complexed autoantibody.

Circulating IgG autoanti-IgE is detectable in a large proportion of individuals with allergic asthma where it is suggested to be potentially involved in the removal of IgE-allergen complexes. Since such a putative role will largely be determined by the subclass profile of complexed (i.e. IgE-bound) IgG anti-IgE, a study was undertaken to determine the subclass distribution of complexed IgG anti-IgE antibody in the sera of asthmatic patients. The study exploits the heat-labile property of IgE by heating (30 min at 56 degrees C) serum to liberate bound anti-IgE, pre- and post-heated sera are then assayed for IgG subclass anti-recombinant human Fc epsilon (rFc epsilon) activities by ELISA and any heat-induced increase in antibody activity is taken as a measure of complexed anti-IgE. This has revealed a disproportionately high amount of IgG4 in complexed (but not free) IgG anti-IgE. The propensity of IgG4 to form complexes with IgE has important biological consequences, particularly with regard to the activation of C1q and Fc gamma R by other subclasses.

Adult

Elucidation of the epitope locations of human autoanti-IgE: recognition of two epitopes located within the C epsilon 2 and the C epsilon 4 domains.

IgG autoanti-IgE is detectable in a large proportion of individuals with allergic asthma, where it is suggested to be potentially involved in modulating IgE-mediated hypersensitivity. Using a series of overlapping recombinant human epsilon-chain peptides, we have shown that circulating IgG anti-IgE antibodies recognise at least 2 epitopes located within the C epsilon 2 and the C epsilon 4 domains, respectively. The C epsilon 2 recognition site is located within the C-terminal portion of the C epsilon 2 domain (i.e. aa301-339) which is thought to contribute residues to the Fc epsilon RI-binding site on IgE. The recognition by autoanti-IgE of an effector function site of such pivotal importance in IgE-mediated hypersensitivity suggests that it plays a possible modulatory role during mast cell and basophil activation.

Adult

Aspects of the pathological significance of IgG4.

Depending on the circumstances, an IgG4 antibody response could have consequences which are either detrimental or beneficial for health. Because of its role in allergic disease and its modulatory effect on other immunoglobulin classes (IgE in particular) and subclasses, IgG4 will continue to be the subject of intensive research. There is, however, an urgent need to develop reagents which would render the detection of IgG4 variants 'a' and 'b' routine, so that their biological and antibody characteristics could be understood.

Humans

Study of IgG sub-class antibodies in patients with milk intolerance.

An ELISA was applied to measure IgG sub-class antibodies to cow's milk beta-lactoglobulin (BLG), alpha-lactalbumin (ALA) and alpha-casein (AC) and to hen's egg ovalbumin (OA) in the sera of nineteen adult patients with milk intolerance causing either asthma, eczema or both. Results were compared with those of forty blood donors and twenty adult patients with either asthma or eczema due to inhalant allergy. Apart from one blood donor, high titres of IgG sub-class antibodies to all three milk proteins were found only in the milk intolerance group. The most frequently detected antibody was AC-specific IgG4; being high (i.e. greater than 9.98 micrograms/ml) in eight milk intolerance cases: six with eczema, one with asthma and one with both. A variable proportion of these eight patients also had high levels of IgG1, IgG2 and IgG3 antibodies to AC and IgG1, IgG2, IgG3 and IgG4 antibodies to BLG and ALA. In contrast, IgG antibody to the egg protein, OA, was remarkably restricted to IgG4 and was present in high titres in 68.4% of milk intolerant patients, 60% of inhalant allergy patients and 30% of blood donors. However, the greater incidence of high titres of IgG4 antibody to OA, compared to AC, was due to the superior coating efficiency of OA resulting in a more sensitive assay. We conclude that some adult cases of milk intolerance, particularly those with eczema, can be diagnosed by detecting raised serum levels of IgG sub-class antibodies to milk proteins.

Adolescent

Detection of an IgM antiglobulin in the sera of atopic patients using insolubilized IgG4, and its capacity to release histamine from leucocytes.

ELISA plates coated with highly pure IgG4 were employed to detect IgM antiglobulin in atopic sera. The use of IgG4, rather than whole IgG, on the solid-phase was to provide direct evidence for the IgG4 reactivity of the antiglobulin. Bound IgM was shown to be antiglobulin in that binding can be inhibited by pre-absorption of serum with IgG. Some 75% of asthmatic patients and 29% of eczema patients were found to have significantly raised level of IgM antiglobulin. This antiglobulin resembles rheumatoid factor in that it appears to be directed against antigenic determinants common to human and rabbit IgG. Isolated antiglobulin-enriched IgM fractions released histamine from leucocytes of 7 out of 12 atopic patients. The histamine-releasing capacity of the IgM antiglobulin was shown to be operating via basophil-bound IgG in that the process can be blocked by pre-absorption of the antiglobulin with IgG. Furthermore, heating the antiglobulin-enriched IgM fraction did not affect its histamine-releasing capacity. We conclude that the IgM antiglobulin detectable in our atopic patients may contribute to the pathological changes in them.

Adolescent

RAST-specific IgE in Nigerian asthmatic patients.

This first study of the pattern of allergen-specific IgE in Nigerian asthmatic patients in Zaria shows a significant percentage with specific IgE to Dermatophagoides pteronnyssinus, Aspergillus fumigatus, and Cynodon dactylon (Bermuda grass). Total serum IgE varied in both urban and rural asthmatics with a pattern of low and high levels in all groups.

Adult

The IgG4 subclass.

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Antibodies, Anti-Idiotypic

IgE and IgG4 antibodies to bovine milk fat globule membrane in atopic eczema patients: a study of their occurrence, relevance and antigenic specificity.

IgE and IgG4 antibodies to bovine milk fat globule membrane (FGM) were measured in atopic eczema patients to determine whether their presence would account for allergy to milk in cases where whole or individual milk protein-specific antibodies are not detectable. The study demonstrates that the measurements of IgE and IgG4 antibodies to FGM do not offer any additional diagnostic value in milk exacerbated cases of atopic eczema. Furthermore, cross-inhibition studies with four milk proteins showed that these FGM-reactive IgE and IgG4 antibodies are directed against alpha-casein.

Adolescent

IgG4: a possible mediator of anaphylaxis in a haemophiliac patient.

Immunological investigations have been carried out on a haemophiliac patient who had developed severe anaphylaxis to bovine factor VII administration. Results have shown that the development of anaphylaxis in this patient was associated with a sudden increase in total and specific IgG4 antibodies. The significance of this observation is discussed in relation to current evidence suggesting the involvement of IgG4 antibodies in some anaphylactic conditions.

Anaphylaxis

Antigammaglobulin (rheumatoid factor) activity of human IgG subclasses.

A sensitive radioimmunoassay has been applied to the study of rheumatoid factor activity of IgM and IgG subclasses in serum and synovial fluid of patients with rheumatoid arthritis. Although rheumatoid factor activity was found in all four subclasses, its distribution was not the same as that of the total subclasses in normal sera. Results are discussed in relation to the possible clinical value of measuring IgG rheumatoid factor in sera and synovial fluids of patients with rheumatoid arthritis.

Adult

Elevated serum IgE and IgG4 in patients with atopic dermatitis.

The quantitative measurement of the IgE and IgG subclass levels in the sera of 29 patients with atopic dermatitis has revealed significantly elevated levels of IgE and IgG4 in a relatively high proportion of patients with this condition compared to non-atopic patients with warts and to a group of normal volunteers studied previously. The possible significance of these observations is discussed in relation to current evidence suggesting the involvement of IgG4 in certain immediate-type hypersensitivity disorders.

Adolescent

Asymmetric depression in the serum level of IgG subclasses in patients with nephrotic syndrome.

Thirty-three nephrotic patients were studied for IgG-subclass levels in matched pairs of serum and urinary specimens. Levels in the serum were compared with those found in the sera of non-nephrotic control children and normal adults. Results have shown an asymmetric depression in the serum level of certain IgG subclasses in some patients with minimal-change nephrotic syndrome, focal glomerulosclerosis, and proliferative glomerulonephritis, indicating that the urinary loss of IgG alone cannot account for the low blood levels of this immunoglobulin class in these conditions.

Adolescent