Ten millennia of purifying selection on HLA-B27 reveals an ancient epidemic-scale burden of spondyloarthritis in West Eurasia.
Zheng M · 2026 · Autoimmunity reviews
Reading the original? How to read a paper.
What this paper found
Ancient DNA from nearly 16,000 people shows HLA-B27 was carried by about half of West Eurasians 8,500 years ago and has been steadily selected against ever since, down to about 4 percent today. The gene likely protected against infections in the past, and the disease it predisposes to was once common enough to shape human genetics.
Why this is on the map
Explains why HLA-B27 persists at all: an evolutionary trade-off, which the thread's biology papers assume but rarely state.
On the map under this thread
DOI: 10.1016/j.autrev.2026.104140 · opens in a new tab. The full paper is on the publisher’s site, not here.
Related papers on the board
Papers sharing one or more threads with this one.
HLA-B27-associated gut microbiota and amino acid perturbations promote ankylosing spondylitis through M1 macrophage activation
Gut Microbes
Shows that HLA-B27, the gene most strongly linked to AS, reshapes which bacteria live in the gut and how the body handles certain amino acids, which in turn activates the inflammatory immune cells driving the disease. Suggests targeting the gut and these metabolic changes could become a real treatment route.
Difficult-to- manage and treatment refractory axial Spondyloarthritis: Systematic review and meta-analysis of prevalence and determinants.
Autoimmunity reviews
Pooling 11 studies of 5,648 patients, about one in ten people with axial spondyloarthritis have difficult-to-manage disease despite two or more biologics, and the strongest links were fibromyalgia, smoking and carrying HLA-B27. Persistent symptoms often reflect something other than ongoing inflammation, which changes what the next step should be.
Two patterns of sacroiliac joint bone marrow oedema are apparent in AxSpA determined by HLA-B27 status, body mass index or psoriasis.
Joint bone spine
MRI scans of 203 people with axial spondyloarthritis showed two different patterns of inflammation in the sacroiliac joints: a lower pattern tied to HLA-B27, male sex and X-ray damage, and an upper pattern tied to higher body weight, psoriasis and older age, which responded well to biologics. The disease may follow somewhat different paths depending on genetics versus mechanical load, and the scan can show which.
Why Do Some Therapies Work While Others Fail? Mechanisms of Response and Emerging Treatments in axial Spondyloarthritis: 2026 SPARTAN Annual Meeting Proceedings.
Current rheumatology reports
This 2026 review explains why some drugs work in axial spondyloarthritis and others do not: HLA-B27 can present fragments that expand a specific population of T cells making TNF and IL-17, while IL-23 matters less once inflammation is established, which fits the failure of IL-23 blockers. It names the next targets, including an interferon signature seen in people who fail TNF and IL-17 drugs and a macrophage factor called MIF.