Genetic variations in antibody genes can influence how we respond to infections and vaccines, say two new studies from Sweden’s Karolinska Institute, published in the journal Science. immunity. Researchers mapped variations in immune genes across multiple populations around the world and showed how these variations affect the ability to form neutralizing antibodies against, for example, influenza viruses.
“We show that the genes that enable the body to form antibodies are much more diverse than previously thought. This difference can be seen both in the code and in differences in gene copy number,” said Professor Gunilla Karlsson-Hedesttam from the Karolinska Institutet’s Department of Microbiology, Tumors and Cell Biology, who led the study.
Antibodies, or immunoglobulins (IGs), are produced by the B cells of the immune system and are central to the detection and neutralization of foreign substances. In the first study, researchers described the development of a new targeted sequencing method, ImmuneDiscover, and used it to map antibody genes in 2,486 people from 25 population groups around the world. This method has made it possible to analyze genomic regions that are genetically difficult to reach in far more cases than previously possible.
May increase susceptibility to infections
The most notable finding was a common genetic deletion of six consecutive IGHD genes, the frequency of which varied between population groups. The IGHD gene encodes part of the antibody that recognizes and binds to foreign substances. IGHD deletions occurred in all populations, but were particularly common in people of East Asian origin, with up to 30% of some populations having deletions in both chromosomes, which affected the types of antibodies produced.
The study also identified more than 300 previously unknown genetic variants, which were shown to be present at different frequencies in different population groups.
The human immune system has evolved over thousands of years in populations living in vastly different environments, resulting in local adaptations of antibody genes against major diseases, explains Martin Corcoran, a researcher at Karolinska Institutet’s Department of Microbiology, Tumors and Cell Biology.
“Being able to map these genes in large populations will provide new knowledge about how differences in immune genes influence our physiology in conditions ranging from infections and autoimmune diseases to cancer, and importantly, provide a mechanism for reading our species’ immunological history encoded within our DNA,” he says.
Some antibody reactions may not occur
In the second study, researchers collaborated with the Scripps Research Institute in the US to investigate how genetic differences affect the immune response to influenza viruses. Using a new technology called ISCAPE, also developed at the Carlson Hedestam Institute, they were able to analyze individual B cells from four healthy adults and identify which antibody genes are used to produce neutralizing antibodies against surface hemagglutinin (HA) proteins.
This analysis again showed large differences between individuals and identified common genetic variations that were found to affect the ability to form specific classes of neutralizing antibodies against the part of HA that the virus uses to bind to cells. Importantly, the researchers showed that many of the neutralizing antibodies required the use of antibodies that bind to the IGHD gene, which is absent in many people, and specifically to the more stable stem region of hyaluronan, a critical structure in the development of widespread influenza vaccines.
It turns out that certain types of antibody responses can only occur in people with certain genetic mutations. This shows how important it is to consider genetic diversity when designing globally effective vaccines. ”
Professor Gunilla Karlsson Hedesttam, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
New resources for researchers
As part of the first study, the researchers collaborated with Sweden’s SciLifeLab’s Data Science Node in Precision Medicine and Diagnostics to build an open resource called the Karolinska Institute Adaptive Immune Receptor Gene Variant Atlas KIARVA. This will make available information about antibody gene variation in the world’s population. Through KIARVA, researchers can determine how common different genetic variants are in different regions of the world, facilitating future research into the role of germline-encoded variations in immunoglobulin genes in infection susceptibility, vaccine response, and autoimmune diseases.
Both studies were funded by grants from the Swedish Research Council, the European Research Council (ERC), and the Knut and Alice Wallenberg Foundation. Karolinska Institute doctoral students Alexandra Fischer and Martin Corcoran are co-lead authors of the second study, which was also funded by grants from SciLifeLab and the National Institutes of Health. Martin Corcoran and Gunilla Karlsson Hedestam are the founders of ImmuneDiscover Sweden AB and have filed a patent application for the technology used in their research.
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References:
- Fisher, A.A. Others. (2026) Genetically diverse influenza antibodies highlight the role of IG germline genetic variation and inform population-inclusive vaccine strategies. immunity. Doi: 10.1016/j.immuni.2026.03.002. https://www.cell.com/immunity/fulltext/S1074-7613(26)00113-5
- Corcoran, M. Others. (2026) Ultra-high-throughput IGH genotyping of 25 global populations reveals population-biased allelic diversity and homozygous V and D gene deletions. immunity. Doi: 10.1016/j.immuni.2026.01.026. https://www.cell.com/immunity/fulltext/S1074-7613(26)00047-6
