Just as food and climate vary by location, so do our immune systems. Pollen allergies may be common in one country, yet rare in another; an identical rash in two people might be caused by different local species of dust mites. However, our present-day understanding of human immunity comes largely from data drawn from European populations, leaving many others underrepresented.
A sweeping new survey of immune diversity stands to change that. An international research consortium has recently published the Asian Immune Diversity Atlas (AIDA): a comprehensive immune reference map of multinational Asian populations. Comprising the single-cell RNA sequences of ~1.2 million circulating immune cells from 619 donors, AIDA charts—in molecular detail—how age, sex and ancestry shape healthy immune cell behaviour across seven population groups in five countries.
“The question we sought to answer with AIDA was: how different are we from each other at an immunological level?” said Shyam Prabhakar, Associate Director of the A*STAR Genome Institute of Singapore (A*STAR GIS). “Those differences can shape what counts as ‘normal’ or a ‘healthy baseline’ when diagnosing disease, as well as optimal drug choices and doses.”
The effort united researchers across Asia, including Assistant Director Jay W. Shin and Senior Scientist Kian Hong Kock of A*STAR GIS; Woong-Yang Park of the Samsung Genome Institute, South Korea; Varodom Charoensawan and Ponpan Matangkasombut of Mahidol University, Thailand; Partha Majumder of the John C. Martin Centre for Liver Research and Innovations, India; and dozens of others from institutes across India, Japan, Singapore, South Korea, Thailand and the US. Prabhakar, Shin and Park are cofounders of the AIDA consortium, which commenced during Shin’s tenure at RIKEN, Japan.
AIDA uncovered many genetic variants, common in Asia but rare elsewhere, which affected immune cells and are linked to differences in disease risk. These included rs2230500, a rheumatoid arthritis-linked variant that AIDA correlated with the expression of a hypoxia-related gene.
“We’ve also found the pervasive effects of sub-continental diversity on a range of traits, such as variations in cellular abundance or gene expression patterns between Singapore’s ethnic communities,” said Shin. “AIDA shows that ‘Asians’ cannot be treated as a single group; there are meaningful biological differences.”
Some discoveries were especially unexpected, such as how South Korean donors had significantly lower levels of regulatory T cells—a cell type vital for preventing autoimmune issues—compared to other AIDA cohorts. Age and sex differences also manifested differently across populations; for example, the abundance of CD4+ T naïve cells—a cell type implicated in autoimmune diseases such as lupus— shifted differently with age in South Korean, Singaporean Chinese and Singaporean Malay donors.
“Our findings suggest that reference ranges for immune cells need to account for multiple dimensions of human diversity, including sex, age and self-reported ethnicity,” said Kock.
The team hopes AIDA will support next-generation clinical diagnostics by pinpointing disease-related cell subtypes, states and gene expression patterns. “AIDA also provides a blueprint for global precision medicine efforts,” said Prabhakar. “We’re continuing to add new populations and expand into new analyses, such as ageing-related changes, to close research gaps and extend healthspans worldwide.”
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Genome Institute of Singapore (A*STAR GIS).
