Creation of Asian Immune Diversity Atlas - Multinational study establishes health standards

The Human Cell Atlas (HCA) Consortium is an international research consortium that aims to create a comprehensive reference map of all cells in the human body to deepen understanding of human health and promote disease diagnosis, monitoring, and treatment. Currently, approximately 3,900 researchers from 104 countries are involved. As one of its major projects, the Asian Immune Diversity Atlas (AIDA) Consortium, formed by researchers from five countries—Japan, Singapore, South Korea, Thailand, and India—has created the world's first AIDA by conducting a multinational study of immune cells in human blood at single-cell resolution. This is expected to provide insights into the genetic diversity of Asian populations and contribute to the stratification of disease risk, diagnostic criteria, and determination of treatment targets for Asians. From Japan, the RIKEN Center for Integrative Medical Sciences participated in this research. Their findings were published in Cell.

Previous genomic research has primarily focused on European populations, leading to insufficient understanding of genetic variations in other populations. The AIDA Consortium used single-cell genomics technology to profile 1,265,624 immune cells from blood samples of 625 healthy donors living in the five Asian countries. They analyzed how ancestry (genetic background), age, and gender affect immune cell characteristics, and created AIDA as a baseline that shows reference information on the immune cells of healthy Asians and predicts abnormalities and disease risks among Asian populations.

The analysis revealed several characteristics of immune cells in blood among populations with different genetic backgrounds. Blood samples from donors living in Thailand showed a lower-than-average proportion of monocytes, a type of white blood cell. Meanwhile, blood samples from donors living in South Korea showed very low proportions of regulatory T cells (Tregs), white blood cells involved in autoimmune diseases.

Donors living in South Korea and Chinese/Malay donors living in Singapore showed differences in age-related variation trends in CD4⁺ T naïve cell subtypes. In contrast, no differences were observed in donors living in Japan and Thailand. The researchers discovered that the levels of CD4⁺ T naïve cell subtypes differ depending on self-reported ethnicity and age, even among healthy donors.

This means that when using CD4⁺ T naïve cell levels as a diagnostic marker, it is necessary to consider both self-reported ethnicity and age in diagnosis, as the proportion of CD4⁺ T naïve cell subtypes differs due to genetic background and other factors.

For genetic mutations that have been identified as potential causes of diseases in previous studies of human populations, including Japanese cohorts, AIDA also identified candidate cell types and genes affected by these mutations. For example, the rs2230500 gene mutation associated with rheumatoid arthritis is found in Japanese donors and is common in East Asia but rare in non-Asian populations. The newly created AIDA indicates that genes such as HIF1A, which responds to low oxygen, and B cell subtypes involved in immune responses to pathogens are candidates for genes and cell types affected by rs2230500.

The AIDA created in this study is expected to deepen understanding of immune diversity in Asia by providing reference information on the immune cells of healthy people in each Asian population, while enabling stratification of disease risk, improved accuracy of diagnostic criteria, and personalized treatment for Asian populations. It may also lead to more accurate and effective medical interventions. Furthermore, the valuable insights gained into genetic mutations specific to Asian populations have demonstrated the importance of diversity in genomic research.

Journal Information
Publication: Cell
Title: Asian diversity in human immune cells
DOI: 10.1016/j.cell.2025.02.017