<During the last few years, more than 30% of the population has been diagnosed with asthma.
The WHO has recently focused on asthma because of its rapidly increasing prevalence, affecting up to 100 millions of people, and the mortality is about 180000 cases/year.
Asthma is a disorder of the conducting airways characterized by TH2-mediated inﬂammation and enhanced mediator release; the symptoms are variable airﬂow obstruction highly responsive to inhaled corticosteroids, wheezing, shortness of breath, chest tightness, and coughing,
IgE sensitization to airborne particles is a hallmark of asthma.
Some persons may have an abnormality called atopy, a hereditary predisposition to the development of immediate hypersensitivity reactions against common environmental antigens. These individuals suffer by IgE regulatory defects that allow nonparasitic antigens to stimulate inappropriate IgE production, leading to tissue-damaging type I hypersensitivity.
The term allergen refers specifically to nonparasitic antigens capable of stimulating type I hypersensitive responses in allergic individuals.
Allergens are small proteins or protein-bound substances having a molecular weight between 15,000 and 40,000.
The abnormal IgE response of atopic individuals is at least partly genetic: one locus, on chromosome 5q, is linked to a region that encodes a variety of cytokines, including IL-3, IL-4, IL-5, IL-9, IL-13, and GM-CSF; a second locus, on chromosome 11q, is linked to a region that encodes the β chain of the high-affinity IgE receptor.
The cells that bind IgE are blood basophils and tissue mast cells, and they bind IgE by two different receptors: FcεRI and FcεRII.
The bound is calling cross-linkage.
It is well known that allergens initiate IgE-mediated inﬂammation by activating mast cells and basophils via binding to IgE and crosslinking of surface high-afﬁnity IgE receptors (FcεRI), causing degranulation within minutes. This process accounts for the early-phase response to allergen. The mast cells and basophils then produce newinﬂammatory mediators within hours, resulting in inﬂux of additional inﬂammatory cells and worsening of airway inﬂammation, which accounts for
the late early-phase response.
In summary, IgE plays a major role in the development of asthma, in airway inﬂammation, in both intrinsic and extrinsic stable asthma, in asthma exacerbations, and in long-term decline in lung function. Therefore, blocking IgE function was predicted to beneﬁt patients with asthma.
The New Therapy: OMALIZUMAB
Omalizumab (Xolair) is a humanized monoclonal antibody used in the treatment of adolescent and adult patients with moderate to severe allergic asthma
It is a biotechnological product, the first in allergic pathology. It could turn off the pathology from the apical effect. Omalizumab is a murine IgG1, humanized.
How it work?
Anti-IgE antibodies bind to the constant region 3 of the IgE heavy chain (CHε3) at the binding sites for the high-afﬁnity (FcεRI), and the low-afﬁnity (FcεRII or CD23
) IgE receptors.
This event prevents IgE binding to IgE receptors on basophils and mast cells. Omalizumab prevents IgE-mediated activation of basophils and mast cells, because the bound with anti-IgE have the same binding afﬁnity as does FcεRI.
Omalizumab was approved by the FDA
in 2003. Omalizumab has been administered via subcutaneous, that was selected as the most practical for clinical use.
The dose is 0.016 mg/kg per IU/ml of total serum IgE given for each four-week period. It is possible to calculate the appropriate dose based on the patient’s weight and total serum IgE.
Since November 2006, Omalizumab was approved also in Italy, by the AIFA.
Common side effects are pain, induration, erythema, burning sensation, warmth, and localized hive formation, headache, virus and upper respiratory infection… the follow-up are ongoing to study the serious adverse events (clinical trials