Researchers Explore Mechanisms of Allergic Disease

CD14 A POTENTIAL TARGET FOR PROBIOTICS

Researchers have discovered that the molecule CD14 may be a potential target for preventative measures against atopic disease. These findings were presented today at the 2005 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) in San Antonio.

Promising results have recently been reported from studies using probiotics, microbes that beneficially stimulate the host's immune system and intestinal microbes, to reduce the risk of atopic disease in infancy and childhood. However, the mechanisms by which probiotics might exert their effect remain unclear. Samuli Rautava, MD, and colleagues from the University of Turku, FINLAND, investigated the role of the molecule CD14 in the development of atopic disease. Eighteen infants received a mixture of probiotics during the first year of life and 20 received a placebo mixture. Researchers found that probiotics increased the serum level of soluble CD14 at one year of age compared to infants who received the placebo.

These results suggest that specific probiotics may enhance healthy hot-microbe interaction through the molecule CD14 and influence the development of atopic disease in infancy.

NON-CANONICAL GENE SPLICING ESSENTIAL TO AUTOIMMUNE DISEASES

Researchers believe that non-canonical gene splicing is an essential feature for most proteins involved in autoimmune diseases. These findings were presented today at the 2005 AAAAI Annual Meeting in San Antonio.

When genes are encoded into proteins, unwanted internal segments are removed in a process called splicing. The canonical form of splicing occurs in more than 99% of regular proteins. However, in proteins that are targets of autoimmune diseases, canonical splicing is significantly reduced, and another form of splicing called non-canonical splicing occurs more frequently.

To determine to what extent non-canonical splicing takes place, Bernard Ng, MD, and colleagues from Baylor College of Medicine, compared 45 randomly selected proteins associated with autoimmune diseases to 9,554 randomly selected proteins from the human genome.

Researchers discovered that 80% of the autoimmune disease proteins underwent non-canonical splicing, which was significantly higher than the less than 1% rate found in the human genome proteins. These findings demonstrate the potential power of mining the human genome sequence for understanding the molecular mechanisms by which autoimmune diseases develop. Defining the molecules targeted by the immune system in these diseases should also enable the development of novel therapies.

HIGH DOSE OF AN ALLERGEN PREVENTS ALLERGIC SENSITIZATION

A new therapy called high dose allergen exposure may prevent the development of allergies, according to new research presented at the 2005 AAAAI Annual Meeting in San Antonio.

Marc A. Riedl, MD, and colleagues from the David Geffen School of Medicine at UCLA, using a human nasal allergic sensitization model, examined the effect of nasal allergen dose on the likelihood of becoming allergic to that specific allergen. A protein called keyhole limpet hemocyanin (KLH) was used as the model allergen due to its safety and rare chance of exposure in everyday life.

Allergic individuals completed a series of nasal sprays with varying doses of KLH. At the end of the study, nasal washes were examined for allergic antibodies to KLH. Upon examination, researchers discovered:* At low dose of KLH " 100% of the patients became allergic * At medium dose of KLH " 57% became allergic* At high dose of KLH" only 11% developed an allergy

These results suggest that a high dose of an initial exposure to an allergen may teach the immune system to "tolerate" the allergen rather than produce an allergic reaction. Future research will test whether high dose allergen exposure is a useful therapy to prevent allergies from ever developing in certain individuals.

TOLL-LIKE RECEPTOR 7 PLAYS A ROLE IN DECREASING ASTHMA

The activation of toll-like receptor 7 plays an important role in the onset of asthma, according to new research presented today at the 2005 AAAAI Annual Meeting in San Antonio.

Toll-like receptors activate multiple steps in the inflammatory reactions that help eliminate invading pathogens and coordinate systemic defenses. Serder Sel, MD, from Biomedical Research Center, Marburg, Germany, and colleagues evaluated the impact of toll-like receptor 7 (TLR-7) activation on established allergen triggered asthma in mice.

After inducing allergic asthma in mice, researchers administered injections of R-848, a synthetic TLR-7 ligand. They found that the TLR-7 ligand completely reversed allergic asthma in the mice. It suppressed airway eosinophilia, inflammation of the airway mucosa, IgE production and normalized airway responsiveness.

These studies were presented at the 2005 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI). The AAAAI is the largest professional medical specialty organization in the United States representing allergists, asthma specialists, clinical immunologists, allied health professionals and others with a special interest in the research and treatment of allergic disease. Allergy/immunology specialists are pediatric or internal medicine physicians who have elected an additional two years of training to become specialized in the treatment of asthma, allergy and immunologic disease. Established in 1943, the AAAAI has over 6,000 members in the United States, Canada and 60 other countries. The AAAAI serves as an advocate to the public by providing educational information through its Web site, http://www.aaaai.org, and its Physician Referral and Information Line, 1 (800) 822-2762.