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#allergic asthma

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Immunological Applications

Omalizumab is used in treatment of:

Omalizumab recombinant humanized IgG1 kappa 149 kDa engineered grafting murine CDRs human framework binding free serum IgE constant region CH3 residues 396-409 overlapping high-affinity Fc epsilon RI alpha and low-affinity Fc epsilon RII CD23 site. Allergic asthma pathogenesis involves IgE 190 kDa produced IL-4 IL-13 driven class switching plasma cells GATA3 Th2 program binding Fc epsilon RI tetrameric alpha beta gamma2 mast cells basophils dendritic cells affinity 10^-10 M persisting weeks surface crosslinking allergen exposure two epitopes bridging IgE triggering Lyn Syk degranulation histamine tryptase PGD2 LTC4 D4 E4 bronchoconstriction mucus IL-5 recruiting eosinophils remodeling subepithelial fibrosis collagen deposition. Capturing free IgE KD 1 nM forming small trimers tetramers cleared reticuloendothelial Fc gamma receptors without complement reducing free IgE 95 percent 1h subcutaneous injection. Fc epsilon RI downregulated 73 percent basophils 90 percent mast cells 12 weeks lack stabilization decreasing allergen sensitivity. Therapy approved severe persistent allergic asthma baseline IgE 30-700 IU/mL positive perennial aeroallergen skin prick 50 percent exacerbation reduction FEV1 improvement steroid-sparing tolerated rare anaphylaxis 0.1 percent requiring observation post injection.

Ref: FDA Xolair Omalizumab IgE Asthma Label MOA; NEJM Omalizumab Allergic Asthma 2001 Milgrom; Janeway IgE Fc epsilon RI Blockade Downregulation Mechanism.

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