Scientists find that a specific variant of the HLA-DPB1 gene is associated with poor responsiveness to allergy treatment

Seasonal allergies are very common in some parts of the world. In Japan, it is estimated that about one-third of the population is allergic to pollen from Japanese cedar, a native tree species, making Japanese cedar pollinosis one of the most common allergic diseases in the country. Fortunately, allergen immunotherapy has come a long way in recent decades, becoming the closest thing to a cure for seasonal and year-round allergies. In sublingual immunotherapy (SLIT), patients can gradually build up 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.

Although SLIT is beneficial for most people with allergic rhinitis, i.e. those who suffer from inflammation of the inside of the nose after exposure to allergens, the treatment is ineffective for about 20 30% of them. Unfortunately, there is currently no way to tell if SLIT will work for a patient unless they try it and observe their response over as long as two years, which means that 20-30% of patients would have to tolerate all the side effects of the treatment without any benefit, for such a long time.

In this context, a team of Japanese researchers set out to find a biomarker that could be used to predict a person’s reactivity to SLIT for Japanese cedar pollinosis. In their latest article, published online on 12and February 2022 in Allergy, they report a newly discovered association between a specific variant of the HLA-DPB1 gene and a poor response to SLIT. This work is the result of a collaborative effort led by Prof. Shigeharu Fujieda and Dr. Masanori Kidoguchi of Fukui University, and Prof. Emiko Noguchi of the University of Tsukuba.

So what is the HLA-DPB1 gene and why would it be related to its reactivity 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 forms a functional protein complex with the protein encoded by the HLA-DPA1 uncomfortable. However, these genes are highly polymorphic, which means that there are a large number of genetic variants (alleles). In previous studies, this research team had found that certain structural differences in antigen-binding pockets between HLA-DPB1 the alleles could make an individual more susceptible to Japanese cedar pollinosis and sensitization.

This led them to think that there might also be a link between the alleles of HLA-DPB1 and an individual’s responsiveness to SLIT. To test their hypothesis, they recruited more than 200 Japanese cedar pollinosis patients who underwent SLIT. The researchers determined the HLA-DPB1 alleles in these patients and performed statistical analyzes to see if they were related to their reactivity to SLIT. “OOur results suggest that patients with at least one HLA-DPB1*05:01 allele have an increased risk of not responding to SLIT in their second season of immunotherapy“, says Professor 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 should be noted that this may be the first study to find an association between a genetic biomarker and an individual’s response to allergen immunotherapy. Genotyping HLA-DPB1 could serve as a cost-effective biomarker to predict a given patient’s reactivity to SLIT for Japanese cedar pollinosis, thereby saving valuable time. Moreover, these findings may help researchers around the world rethink how genetic biomarkers can be used in both research and clinical practice, as Professor Fujieda points out: “Our study may result in updates to current international guidelines and consensus documents on the potential of genetic biomarkers.

Hopefully, immunotherapy continues to progress until no one has to suffer the consequences of severe allergies.

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Material provided by Fukui University. Note: Content may be edited for style and length.

Sara H. Byrd