Is it working? Scientists say gene variant indicates effectiveness of immunotherapy for allergies
Scientists discover that a specific variant of the HLA-DPB1 gene is
associated with poor responsiveness to treatment for allergies

Date:
March 7, 2022
Source:
University of Fukui
Summary:
Although sublingual immunotherapy (SLIT) has become an effective
treatment option for many allergies, about 20-30 percent of
patients don't respond to SLIT for Japanese cedar pollinosis --
a highly common disease. In a recent study, scientists reported
that a specific variant of the HLA-DPB1 gene is associated with
poor response to this treatment, highlighting the potential of this
and similar genes as relevant biomarkers in clinical practice for
predicting one's responsiveness to allergen immunotherapy.



FULL STORY ========================================================================== Seasonal allergies are very widespread in certain parts of the world. In
Japan, it is estimated that about one third of the population is allergic
to the pollen of the Japanese cedar, a native tree species, making
Japanese cedar pollinosis one of the most common allergic diseases in
the country. Luckily, allergen immunotherapy has progressed much over
the past few decades, becoming the closest thing we have to a cure for
both seasonal and year-round allergies.

In sublingual immunotherapy (SLIT), patients can gradually develop
immunity to a given allergen by regularly placing small, concentrated
doses of it under their tongue. After several months, a good percentage
of patients find themselves reacting much less severely when exposed to
the same allergens in their daily lives.


========================================================================== While SLIT is beneficial for most people with allergic rhinitis --
that is, those who suffer from inflammation of the inside of the nose
after allergen exposure -- the treatment is ineffective for about 20-30%
of them.

Unfortunately, there is currently no way of telling if SLIT will be
effective for a patient short of trying it out and observing their
response over a period of as long as two years, meaning that 20-30% of
patients would have to tolerate all the side effects of the treatment
for no benefit, for that long a period.

Against this backdrop, a team of researchers from Japan set out to
find a biomarker that could be used to predict the responsiveness of a
person to SLIT for Japanese cedar pollinosis. In their most recent paper, published online on 12th February 2022 in Allergy, they report a newly discovered association between a specific variant of the HLA-DPB1 gene
and poor response to SLIT. This work was the result of a collaborative
effort led by Prof. Shigeharu Fujieda and Dr. Masanori Kidoguchi of the University of Fukui, and Prof. Emiko Noguchi of the University of Tsukuba.

So, what is the HLA-DPB1 gene and why would it be related to one's responsiveness to SLIT? This gene provides instructions for making
a protein that plays a critical role in the immune system: helping
it distinguish the body's own proteins from proteins made by foreign
invaders, such as bacteria and viruses. The protein encoded by the
HLA-DPB1 gene forms a functional protein complex with the protein encoded
by the HLA-DPA1 gene. However, these genes are highly polymorphic, meaning
that a large number of genetic variants (alleles) exist. In previous
studies, this research team had discovered that certain structural
differences in the antigen-binding pockets between HLA-DPB1 alleles
could make an individual more susceptible to Japanese cedar pollinosis
and sensitization.

This led them to think that there might also be a connection between
the alleles of HLA-DPB1 and an individual's responsiveness to SLIT. To
test their hypothesis, they enrolled over 200 patients with Japanese
cedar pollinosis who underwent SLIT. The researchers determined the
HLA-DPB1 alleles in these patients and conducted statistical analyses to
see if they were related to their responsiveness to SLIT. "Our results
suggest that patients carrying at least oneHLA-DPB1*05:01allele have an increased risk of being non-responders to SLIT in their second season of
the immunotherapy," says Prof. Fujieda. "This implies that differences
in the antigen-binding pocket on the HLA-DPB1 protein may influence the
effect of allergen immunotherapy," he adds.

It is worth noting that this may be the first study ever to find an
association between a genetic biomarker and an individual's response
to allergen immunotherapy. Genotyping the HLA-DPB1 gene could serve
as a cost-effective biomarker to predict the responsiveness of a
given patient to SLIT for Japanese cedar pollinosis, saving valuable
time. Moreover, these findings may help researchers worldwide rethink how genetic biomarkers can be used both in research and clinical practice,
as Prof. Fujieda remarks: "Our study could prompt updates in current international guidelines and consensus documents on the potential of
genetic biomarkers." Let us hope immunotherapy keeps advancing until
no one has to suffer the consequences of severe allergies.

========================================================================== Story Source: Materials provided by University_of_Fukui. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Masanori Kidoguchi, Wataru Morii, Emiko Noguchi, Atsushi Yuta,
Yukiko
Ogawa, Takako Nakamura, Hirotaka Kikuoka, Hideaki Kouzaki,
Hiroyuki Arai, Rieko Ii, Naoto Adachi, Keisuke Koyama, Takahiro
Ninomiya, Yoshimasa Imoto, Masafumi Sakashita, Shigeharu
Fujieda. HLA‐DPB1*05:01 genotype is associated with
poor response to sublingual immunotherapy for Japanese cedar
pollinosis. Allergy, 2022; DOI: 10.1111/all.15254 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220307091716.htm

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