In some regions of the world, seasonal allergies are fairly common. Japanese cedar pollinosis is one of the most prevalent allergy disorders in Japan, where it is believed that around one-third of the population is allergic to the pollen of this native tree species. Fortunately, allergen immunotherapy has advanced significantly over the past few decades and is now the most effective treatment option available for both seasonal and year-round allergies.
By applying small, concentrated doses of an allergen under the tongue on a daily basis, patients undergoing sublingual immunotherapy (SLIT) can progressively develop immunity to the allergen. After a few months, a sizable portion of patients notices that their reactions to the same allergens in normal life are substantially milder.
While the majority of patients with allergic rhinitis, or those who experience inflammation of the nose following exposure to allergens, benefit from SLIT, roughly 20–30% of them do not.
Sadly, there is currently no way to determine whether SLIT will be effective for a patient other than to try it out and monitor their response over a period of up to two years. This means that 20–30% of patients would have to tolerate all of the treatment’s side effects for that long of a time without receiving any benefit.
In light of this, a group of Japanese researchers set out to identify a biomarker that may be used to gauge an individual’s propensity to respond 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.
Our results suggest that patients carrying at least one HLA-DPB1*05:01 allele have an increased risk of being non-responders to SLIT in their second season of the immunotherapy. This implies that differences in the antigen-binding pocket on the HLA-DPB1 protein may influence the effect of allergen immunotherapy.
Professor Shigeharu Fujieda
So, what is the HLA-DPB1 gene and why would it be related to one’s responsiveness to SLIT?
This gene gives instructions for producing a protein that is essential for the immune system’s ability to distinguish between proteins manufactured by the body’s own cells and those produced by foreign invaders like 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.
These genes, however, are extremely polymorphic, which means that numerous genetic variations (alleles) occur. This research team has previously found that specific structural variations in the antigen-binding pockets between HLA-DPB1 alleles may increase a person’s susceptibility to Japanese cedar pollinosis and sensitization.
They concluded that there might potentially be a relationship between an individual’s reactivity to SLIT and the HLA-DPB1 alleles. They enlisted more than 200 individuals with Japanese cedar pollinosis who underwent SLIT in order to test their theory. The HLA-DPB1 alleles were identified in these individuals, and statistical studies were carried out to assess whether they were associated with their response to SLIT.
“Our results suggest that patients carrying at least one HLA-DPB1*05:01 allele 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.”
Hope that immunotherapy keeps improving so that no one has to experience the negative effects of severe allergies.
