Association between specific human leukocyte antigen alleles and development of thyroid immune-related adverse event
Creators: name: Sasaki, Eisaku
name: Natori, Yutaka
name: Tokuda, Emi
name: Kimura-Tsuchiya, Reiko
name: Suga, Junko
name: Kanazawa, Kenya
name: Koguchi, Tomoyuki
name: Kikuchi, Nobuyuki
name: Okabe, Naoyuki
name: Murono, Shigeyuki
name: Tachibana, Kazunoshin
name: Soeda, Shu
name: Shimabukuro, Michio
name: Saji, Shigehira
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Space Science
subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Physiology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Developmental Biology
subject: Cancer
subject: Mental Health
subject: Infectious Diseases
subject: FOS: Health sciences

description: <b>Aim:</b> Inherent variations in human leukocyte antigen (HLA) alleles have been revealed epidemiologically to influence the development of autoimmune diseases. HLA alleles may thus also be associated with the development of immune-related adverse events (irAEs), such as thyroid irAE. <b>Materials &amp; methods:</b> In this case–control study, 71 cancer patients who received immune checkpoint inhibitors were enrolled and HLA-genotyped and the frequency of HLA alleles was compared. <b>Results:</b><i>A*26:01</i>, <i>DPA1*01:03</i> and <i>DPB1*02:01</i> were significantly more frequent in patients with thyroid irAE than in patients without any irAEs (35.0 vs 3.2% [<i>p</i> = 0.004], 80.0 vs 45.2% [<i>p</i> = 0.020] and 55.0 vs 25.8% [<i>p</i> = 0.044], respectively). <b>Conclusion:</b><i>A*26:01</i>, <i>DPA1*01:03</i> and <i>DPB1*02:01</i> appear to be associated with thyroid irAE. Everyone has a unique combination of human leukocyte antigens (HLAs) in their body that help the immune system identify threats. HLAs were named from the fact that they were first identified on the surface of human leukocytes. Afterward, HLAs were also found on all human cells. HLAs present antigens to immune cells. These HLAs also influence how the immune system attacks cancer cells. Immune checkpoint inhibitors are drugs that can help the immune system fight cancer, but they sometimes cause severe adverse events. In this study, we investigated whether specific HLA genes are related to the development of an adverse event that affects the thyroid in cancer patients treated with immune checkpoint inhibitors. We found an association between three HLA genes (<i>A*26:01</i>, <i>DPA1*01:03</i> and <i>DPB1*02:01</i>) and the development of the thyroid adverse event. However, larger studies are needed to confirm and generalize these initial exploratory findings. Variations in HLA alleles may be associated with the development of immune-related adverse events (irAEs). We found specific HLA alleles that were highly frequent in patients with thyroid irAE. Human leukocyte antigen (HLA) alleles may influence the development of immune-related adverse events (irAEs) affecting the thyroid. In the present case–control study, 71 cancer patients who received immune-checkpoint inhibitors (ICIs) were divided into groups and the frequency of the HLA alleles in the groups was compared. <i>A*26:01</i> was significantly more frequent in the thyroid-irAE group than in the no-thyroid-irAE group (35.0 vs 7.8% [<i>p</i> = 0.009]). <i>A*26:01, DPA1*01:03</i> and <i>DPB1*02:01</i> were significantly more frequent in the thyroid-irAE group than in the no-irAE group (35.0 vs 3.2% [<i>p</i> = 0.004], 80.0 vs 45.2% [<i>p</i> = 0.020] and 55.0 vs 25.8% [<i>p</i> = 0.044], respectively). <i>DPA1*01:03</i> was significantly more frequent in the other-irAE group than in the no-irAE group (75.0 vs 45.2% [<i>p</i> = 0.046]). <i>A*26:01</i> and <i>DPB1*02:01</i> appeared to be specific for the thyroid irAE group; in contrast, <i>DPA1*01:03</i> was found to be in common between the thyroid-irAE group and the other-irAE group. The frequency of the combination of <i>A*26:01</i> and <i>DPA1*01:03</i> was significantly higher in the thyroid-irAE group than in the no-thyroid-irAE group (25.0 vs 3.9% [<i>p</i> = 0.016]). The odds ratio of <i>A*26:01, DPA1*01:03</i> and <i>DPB1*02:01</i> for the development of thyroid irAE was 16.2, 4.9 and 3.5, respectively. The combination of <i>A*26:01</i> and <i>DPA1*01:03</i> showed the highest odds ratio of 20.3. The median time to onset of thyroid irAE was shorter in patients with <i>A*26:01</i> than in all patients overall (53 vs 72 days). Our results indicate that HLA genotyping prior to the administration of ICIs may help predict the risk of thyroid irAE development.