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Cincinnati Children's Hospital Medical Center Location S
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Cell Type May Help Explain Why Some People Have Dangerous Food Allergies
CINCINNATI--Researchers have discovered a new cell type
that appears to drive life-threatening food allergies and may help
explain why some people get severe allergic reactions and others do not.
Reporting their study data Sept. 22, 2015, in the journal Immunity, scientists at Cincinnati Children's Hospital Medical Center
say their findings in mice should also provide insights into new
therapeutic strategies and diagnostics for food allergies and
anaphylactic shock triggered by the immune antibody IgE (immunoglobulin
E).
The authors report discovery of what they
call "IL-9-producing mucosal mast cells" or (MMC9 cells). The cells
produce large amounts of an inflammatory immune protein called
interlukin 9 (IL-9), which amplifies anaphylactic shock in response to
ingested food. Prior to this study, the primary cellular source of IL-9
was unknown, according to the authors.
"Our
study suggests that although you need to have some level of IgE to
trigger a food allergy response, you also have to produce MMC9 cells to
get a severe response and anaphylaxis," says Yui-Hsi Wang, PhD, lead
investigator, a researcher in the Division of Allergy and Immunology at
Cincinnati Children's and an assistant professor of pediatrics at the
University of Cincinnati College of Medicine. "Without these cells you
will not get severe food allergies."
Set off by
certain foods like peanuts, shell fish and a host of others,
IgE-associated food sensitivity prompts the immune systems of some
children to surge out of control. Unless there is immediate medical
intervention, this can trigger a molecular chain reaction in the
intestines and other organs – leading to diarrhea, hypothermia,
respiratory distress and shock.
About 40
percent of children have some IgE-associated food sensitivity, but only 8
percent of the 40 percent develop the severe food reactions that can
lead to anaphylactic shock, according to Wang.
"Unfortunately
the best medical intervention for these allergies remains avoiding the
foods that cause them," he said. "We don't know why some patients
develop such a strong response and why some don't. This is where we as
basic scientists are coming in to see if we can use mouse models to
learn this, because mice are very much like humans."
Wang
and his colleagues suspect that some people are wired genetically to
have higher or lower susceptibility to severe IgE-related allergic
reactions. Still, it also remains unknown exactly how genetics
contributes to these molecular chain reactions.
Just
as people with food allergies have different degrees of susceptibility,
so do mice. To account for this, the researchers conducted their study
in several distinct strains of genetically bred mice. They gave the mice
an egg white protein called ovalbumin to trigger allergic reactions and
study biological reactions in the animals.
They
observed that after allergic sensitization, some mouse strains
generated large populations of MMC9 cells while other strains did not.
Mice that did not produce MMC9 cells exhibited only minor allergic
responses. Mice that produced intestinal MMC9 cells all had severe
allergic reactions, regardless of whether they had low or high levels of
IgE.
Wang and his colleagues report that
production of MMC9 cells required the presence of type-2 CD4+ T helper
immune cells and the proteins interlukin-4 and STAT6. By producing
significant amounts of IL-9, the MMC9 cells caused mastocytosis and the
production of mast cells, which may migrate out of the intestines to
other organs as they secrete histamines and other molecules that cause
anaphylaxis.
To verify that MMC9 cells were
fueling severe allergic reactions in the mice, the researchers treated
the mice with an antibody, which eliminated the cells and decreased food
allergy symptoms. When MMC9 cells were transferred back into the same
mice, the animals resumed exhibiting food allergy symptoms.
Researchers
next conducted tests to see if their identification of MMC9 cells was
relevant to the development of human food allergies. Analyzing small
intestine biopsy samples from food allergy patients (who gave authorized
consent) the scientists looked for molecular signatures of MMC9 cells.
They found significantly increased expression of the Il9 genetic
transcript and other related transcripts in the samples of food allergy
patients, suggesting a possible connection.
Wang
said the researchers are now trying to find the human equivalent
(orthologue) of the MMC9 cells they found in their mouse models. One
goal the researchers have is to identify that cell and its biological
mediators to see if it possible to develop a biomarker that might allow
development of a blood test for food allergies. Eventually, Wang said,
the team wants to develop a blood test that would allow clinicians to
determine which patients are at higher risk for severe food allergies,
and to find improved treatments for food allergy.
Also
working with Wang on the study were co-first authors and Cincinnati
Children's colleagues Chun-Yu Chen, PhD and Jee-Boong Lee, PhD the
Division of Allergy and Immunology.
Funding
support for the study came from, the National Institutes of Health
(AI090129-1, A1073553), the Digestive Health Center Pilot and
Feasibility Award (P30 DK078392), the Campaign Urging Research for
Eosinophilic Diseases (CURED) Foundation, the Buckeye Foundation and the
Food Allergy Research Education Fund.
According to these findings and others, that is why I encourage the Medical Practice to perform an Immunoglobulin E, Test in Blood, before any other Allergy Testing.
for comments: Carlos E Mijares, MD, www.carlosmixares@gmail.com
www.centromedicodecaracas.com.ve
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