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Biomedical subjects

F Shakib

Publications and source records attributed to F Shakib.

At least 19 recordsLinked to original sources
PubMed1995

Der p I, a major allergen of the house dust mite, proteolytically cleaves the low-affinity receptor for human IgE (CD23).

The nature of the proteases that cleave CD23 in vivo is of considerable interest, but remains unknown. Here, we demonstrate that Der p I, a major allergen of the house dust mite Dermatophagoides pteronyssinus, cleaves CD23 from the surface of cultured human B cells (RPMI 8866 B cell line). The cleavage of the receptor from the B cell surface was associated with a parallel increase in soluble CD23 (sCD23) in the culture supernatant. Furthermore, the proteolytic effect of Der p I was specific for CD23, since none of the other B cell markers tested (CD20, HLA-DR, CD71 and CD49d) were affected. Labeled antibody experiments and protease inhibition assays clearly demonstrate that Der p I is a cysteine protease that directly cleaves a 25-kDa fragment of CD23. These data suggest that the cysteine protease Der p I, in addition to being highly immunogenic, may up-regulate IgE synthesis by virtue of its ability to cleave CD23.

Allergens↗
PubMed1995

Do autoantibodies to IgE play a role in IgE-mediated events?

Elevated blood levels of IgG anti-IgE are detectable in individuals exhibiting enhanced IgE production, namely those with allergic conditions and helminthic parasite infections. The fact that there are epitope-specific subpopulations of autoanti-IgE suggests that this autoantibody could potentially have multiple effects in immunological events involving IgE.

Animals↗
PubMed1995

Potentiation of in vitro synthesis of human IgE by cyclosporin A (CsA).

In this study, we investigated the modulatory effects of CsA on in vitro synthesis of IgE, IgG1 and IgG4 by human peripheral blood mononuclear cells (PBMC). In contrast to its known immunosuppressive effect, we have demonstrated that a low dose of CsA (10(-7) M, 120 ng/ml) potentiated IgE production by up to 40-fold (i.e. from 33 +/- 4.5 to 1346 +/- 290 ng/ml). This potentiation was specific for IgE since no such effect was demonstrable with IgG1 and IgG4. Potentiation of IgE synthesis by CsA in the PBMC cultures was partly due to CsA acting on T cells, as demonstrated by the addition of CsA-treated T cells to T cell-depleted cultures. However, potentiation was also demonstrable in a T cell-depleted, anti-CD40-stimulated culture (four-fold increase from 400 +/- 48 to 1606 +/- 127 ng/ml). Our data therefore suggest that there are at least two mechanisms for CsA-induced potentiation of IgE synthesis, one T cell-dependent and the other T cell-independent. The clinical implications of these findings are discussed with regard to the use of CsA in the treatment of Th2-mediated diseases.

Adjuvants, Immunologic↗
PubMed1994

In vitro basophil histamine-releasing activity of circulating IgG1 and IgG4 autoanti-IgE antibodies from asthma patients and the demonstration that anti-IgE modulates allergen-induced basophil activation.

In this study we have examined the relationship between the in vitro basophil histamine-releasing activity of human IgG anti-IgE, isolated as euglobulin fractions from sera of asthmatic patients, and its IgG1/IgG4 subclass distribution. In particular, we have investigated whether IgG anti-IgE modulates allergen-induced basophil activation. The study has revealed that only a small proportion of IgG anti-IgE samples triggered histamine release from basophils of an asthmatic individual (4/21; 19%), a hay fever sufferer (4/10; 40%) and a healthy person (7/21; 33%). The basophil histamine-releasing activity of IgG anti-IgE did not seem to be determined by the IgG1/IgG4 subclass composition of the IgG anti-IgE preparation used. Furthermore, we have demonstrated that autoanti-IgE antibodies modulate allergen-induced basophil histamine release. The three modulatory effects exerted by IgG anti-IgE antibodies on allergen-triggered basophil activation (i.e. additive, synergistic and blocking) were not dependent on the subclass nature of IgG anti-IgE or the use of histamine-releasing anti-IgE preparations. Our data suggest that IgG anti-IgE antibodies in asthma patients may consist of two functionally distinct subpopulations: those which up-regulate (pro-allergic) and those which down-regulate (anti-allergic) the allergic release of mediators from mast cells and basophils.

Allergens↗
PubMed1994

Circulating levels of IgG1 and IgG4 anti-IgE antibodies and asthma severity.

In this paper, we have determined the levels of IgG1 and IgG4 anti-IgE in the sera of 66 asthma patients suffering from mild (n = 24), moderate (n = 23), or severe (n = 19) symptoms, and 20 nonatopic, healthy subjects. The study has revealed that although asthma patients have significantly elevated levels of IgG1 and IgG4 anti-IgE antibodies, the concentration of these autoantibodies is not related to the severity of asthma. This conclusion may be related to the known heterogeneity of autoanti-IgE antibodies in terms of their ability to trigger basophil histamine release.

Adolescent↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

The IgG4 subclass.

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Antibodies, Anti-Idiotypic↗