Gene variant may impede sublingual immunotherapy for Japanese cedar allergies
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Researchers have associated a variant of the HLA-DPB1 gene with poor responsiveness to sublingual immunotherapy for Japanese cedar pollinosis, according to a study published in Allergy.
“Our results suggest that patients carrying at least one HLA-DPB1*05:01 allele have an increased risk of being nonresponders to SLIT (sublingual immunotherapy),” Shigeharu Fujieda, MD, PhD, of the division of otorhinolaryngology, head and neck surgery at University of Fukui in Matsuoka, Japan, said in a press release.
“This implies that differences in the antigen-binding pocket on the HLA-DPB1 protein may influence the effect of allergen immunotherapy,” Fujieda said.
Approximately one-third of the population of Japan is allergic to the pollen of the Japanese cedar, but about 20% to 30% of patients do not respond to SLIT, the researchers said.
SLIT often requires up to 2 years before it is effective, leaving these patients to endure its side effects for that long period without benefit, the researchers wrote, but the HLA-DPB1 gene variant may serve as a biomarker to spare these patients from that ineffective care.
HLA-DPB1 provides instructions for making a protein that helps the body distinguish its own proteins from proteins made by bacteria, viruses and other foreign invaders. Structural differences in the antigen-binding pockets between HLA-DPB1 alleles, however, could make individuals more susceptible to Japanese cedar pollinosis and sensitization, the researchers wrote.
The study enrolled 219 patients with Japanese cedar pollinosis who received SLIT over various seasons, including 203 patients available during the time of peak symptoms in the second season. The patients had a mean age of 37.8 ± 18.2 years, and 60.1% of them were male.
According to the study, 160 of the 203 patients during the time of peak symptoms in the second season had a total VAS score of less than 5, indicating responsiveness to SLIT treatment, whereas 43 had VAS scores of 5 or greater, indicating non-responsiveness.
The researchers then identified and analyzed which HLA-DPB1 alleles these patients harbored to see if they were related to the patients’ responsiveness to treatment.
HLA-DPB1*05:01 (39.9%), HLA-DBP1*02:01 (21.2%) and HLA-DPB1*09:01 (9.9%) were the most frequently observed alleles. HLA-DBP1*05:01 carriers showed less improvement in their VAS scores than noncarriers (P = .005).
Also, HLA-DPB1*05:01 carriers had lower expression of IL-10 than noncarriers (P = .04). Regulatory T cells express IL-10 after SLIT, and it is considered an early biomarker of allergen immunotherapy responsiveness.
The researchers said that based on their results, HLA-DPB1*05:01 carriers may be less able to produce Japanese cedar pollen-derived IL-10 after SLIT than noncarriers, leading to non-responsiveness to SLIT.
Also, the researchers said their work may be the first study to associate a genetic biomarker with an individual’s response to allergen immunotherapy. Genotyping the HLA-DPB1 gene could help providers cost-effectively predict a patient’s responsiveness to SLIT for Japanese cedar pollinosis, the researchers wrote, saving valuable time.
These findings additionally could help researchers worldwide rethink how they could use genetic biomarkers both in research and clinical practice, the researchers continued.
“Our study could prompt updates in current international guidelines and consensus documents on the potential of genetic biomarkers,” Fujieda said.