anti-IgE injections effects on allergic reactions.

[RubyViolet]

I was reading this article : http://www.medscape.com/viewarticle/777380_10 but quickly became confused where it said "The complexes of anti-IgE bound to IgE are then cleared from the circulation. Thus, activation of allergic responses, at least to small amounts of peanut protein, can be prevented."

I was wondering if someone could explain to me how reducing circulating IgE concentrations affect the response for peanut allergy. Since the IgE involved in peanut allergy is bound to mast cells by its Fc region, I was wondering if after allergic reactions mast cell numbers are decreased and hence need to make more peanut specific IgE to present on their cell surface.

 

Can anyone help?

[jimmydasaint]

Sorry, I could not read the article as a non-registered person. However, a useful homologous study found the following:

 

Allergic diseases are characterized by biphasic reactions mediated by IgE.18 The immediate reaction appears within minutes after exposure to an antigen, and the late-phase reaction may occur two to eight hours afterward. The latter process is the model for allergic disease.19,20 Lung biopsy21,22 and bronchoalveolar lavage23 in subjects with stable asthma show the presence of inflammation consistent with a late-phase reaction, whereas pulmonary-function tests show hyperresponsiveness of the airway that is proportional to the magnitude of the late-phase reaction.24IgE binds to high-affinity receptors on tissue mast cells and circulating basophils.10,25 In subjects with asthma, there is a correlation between serum IgE concentrations and both airway responsiveness26 and the number of high-affinity receptors.25

Effective allergen immunotherapy attenuates the late-phase reaction.27 However, immunotherapy as currently practiced has not been uniformly effective in the treatment of allergic disease.28,29Consequently, the basis of therapy remains the consistent use of antiinflammatory medication, most often in the form of inhaled corticosteroids, to block the late-phase reaction and reduce airway hyperresponsiveness.8,30 Successful antiinflammatory therapy leads to long-term prevention of the symptoms of asthma by suppressing, controlling, and reversing inflammation.8,30 The clinical efficacy of rhuMAb-E25 may be the result of similar effects on the pathogenesis of the allergic response.

Although immunotherapy is effective only in a narrow, antigen-specific range,9 rhuMAb-E25 removes IgE from the circulation, basophils,10 and mast cells regardless of its antigen specificity.31,32 In this study and in earlier work,5,6 a single dose of rhuMAb-E25 rapidly reduced serum free IgE serum concentrations by more than 95 percent. Although serum free IgE concentrations declined precipitously, mean serum total IgE concentrations, consisting mostly of immunoglobulin complexes, increased over time and appeared to reach a plateau.4 Analytic ultracentrifugation and size-exclusion chromatography identified the largest complexes of rhuMAb-E25 and IgE as heterohexamers with a molecular mass of 1,000,000 or less.33 Because these complexes cannot bind IgE receptors, they lack the biologic activity of IgE. The complexes are cleared by low-avidity interaction with the Fcγ receptors of leukocytes and the reticuloendothelial system.4 These low-molecular-weight complexes, which do not fix complement or accumulate in renal glomeruli, do not pose a risk of immunopathogenicity.4

 

http://www.nejm.org/doi/full/10.1056/NEJM199912233412603#t=articleDiscussion

It appears that there is a combination therapy of anti IgE antibodies and anti-inflammatory drugs and that this combination has the effect of decreasing the allergic response. Other chemicals seem not to act on IgE connected to mast cells but down regulate the manufacture of IgE receptors.

Edited April 8, 2013 by jimmydasaint