Defensive Protein Linked to Asthma

Defensive Protein Linked to Asthma
WEDNESDAY, Nov. 14 (HealthDay News) -- A protein that may haveoriginally evolved to help protect the airways now appears to be abiomarker that indicates severe asthma. And it may also play a role in thedevelopment of asthma, according to new research.
Reporting in the Nov. 15 issue of the New England Journal ofMedicine, Yale University researchers said that people with severeasthma were more likely to have elevated levels of the protein known asYKL-40 in their blood compared to people without asthma.
"We believe that it's a marker of the inflammatory response associatedwith asthma," said the study's lead author, Dr. Geoffrey Chupp, anassociate professor of medicine at Yale University School of Medicine.And, he added, "These new novel family of molecules could be veryimportant in asthma pathogenesis. Down the road, there could be newtreatments and new ways to characterize asthma."
YKL-40 is what's known as a chitinase-like protein. It attaches itselfto chitin, an abundant substance found in fungi, crustaceans and ininsects like dust mites and cockroaches. It's also present in the pharynxand eggs of parasitic worms called helminths. Infection with helminthsused to be common but is now rare in developed countries, according to theauthor of an accompanying editorial in the same issue of the journal, Dr.Burton Dickey, chairman of pulmonary medicine at M.D. Anderson CancerCenter in Houston. These worms migrate through the skin into thebloodstream and travel through the lungs to get into the gastrointestinaltract, he said.
Humans don't manufacture chitin but do produce chitinases (enzymes thatbreak down chitin) and chitinase-like enzymes (enzymes that bind tochitin, but don't break it down). The presence of chitin in the lungs maymake the body believe that it has a helminth infection that it needs todefend against, Dickey said. Unfortunately, he pointed out, this defensemechanism may now be reacting to harmless dust mites instead.
However, both Dickey and Chupp noted that the new study doesn't provethat YKL-40 is a cause of asthma, only that elevated levels appear to be amarker of severe asthma.
Chupp and his colleagues at Yale, the University of Paris and theUniversity of Wisconsin recruited 253 adults -- some with asthma and somewithout. Levels of YKL-40 were measured from blood samples at all threestudy sites. In Paris, the researchers also conducted lung biopsies.
The researchers found that, overall, people with asthma had higherlevels of YKL-40 in both blood levels and in lung biopsies than did peoplewithout the airway disease. In the Yale group, the average levels ofYKL-40 were 49.1 nanograms (ng) per milliliter of blood for people withmild asthma, 58.3 ng per milliliter for controls, 68.4 for those withmoderate asthma, and 77 ng per milliliter for those with severe asthma.The findings were similar in both the Paris and the Wisconsin groups, theresearchers said.
Chupp pointed out that the one of the biggest potential benefits of thenew research is that YKL-40 is easily detected in the blood.
The study's senior author, Dr. Jack Elias, chairman of medicine and aprofessor of immunobiology at Yale, said in a prepared statement: "Thismay allow us to identify a subpopulation of patients with severe asthmaand give us insights into the biologic processes that make the disease sosevere in these individuals.
"Our studies also have demonstrated that eliminating YKL-40 decreasesspecific types of tissue inflammation, which could be of particularbenefit to asthmatic patients with an elevated level of this protein," headded.
Dickey said: "It's always been something of a mystery why asthmaprevalence has risen in the 20th century, and this may help us begin tounderstand it. Chitinase and chitinase-like proteins are a highlyeffective protective response against worms, and for most of humanhistory, we have been burdened with these parasites. An asthma-likeresponse probably evolved to protect against worms. Now it appears thisprotective response may have gone awry and something as harmless as dustmites or pollen is initiating it."
Dickey said if chitin truly is triggering an inflammatory airwayresponse that leads to asthma, these findings could open up whole newavenues of research and new therapies.