SELECTED ARTICLES FROM THE RECENT LITERATURE 2006

12/5/06

Anti-IgE therapy and mast cell stabilization

Summary
Background – Omalizumab (Omal), a monoclonal anti-IgE antibody, has been approved for the treatment of moderate to severe IgE-mediated asthma.  There is continued investigation of the mechanisms underlying the clinical effects of Omal.

Findings – Some findings in the continued investigation of Omal effects were reviewed by Chang and Shiung of the National Tsing Hua Univ in Taipei, Taiwan.  They pointed out that original studies focused on the capacity of Omal therapy to inhibit binding of IgE to its high affinity receptor (Fc epsilon R I) on mast cells and basophils.  However, subsequent studies showed that within weeks to months of Omal therapy, the expression of Fc epsilon R I itself is reduced gradually to less than 5% of that present before Omal treatment.  Thus, mast cells and basophils of Omal-treated patients become much less sensitive to react with challenging allergens with a resultant marked decrease in mediator release.

Reference
J Allergy Clin Immunol 2006;117:1203-12

Editor's Comments
A key property of Omal leading to beneficial clinical effects is that it blocks binding of IgE to its high affinity receptor but does not activate mast cells and basophils already expressing IgE on their surface. This is in contrast to the effects of a number of polyclonal heterologous anti-IgE antibodies (made in the research lab) which activate such IgE-bearing mast cells and basophils.

The findings about a marked decrease in Fc epsilon R I expression during Omal therapy raise the possibility that Omal treatment may also be helpful in some patients with chronic idiopathic urticaria (CIU).  It has been found that the serum of about 30% of CIU patients contains increased levels of IgG antibodies directed against the Fc epsilon R I.  Although the pathogenic role of such antibodies in CIU are still not established, it is conceivable that depletion of Fc epsilon R I expression on mast cells and basophils may prevent a pathogenic interaction in CIU.

 

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