Some joints may be primed for rheumatoid arthritis before birth: Science Daily

[Mij]

Why rheumatoid arthritis attacks some joints but spares others may be determined partly before birth

Date: September 5, 2026

Source: University of Oxford

Summary: Scientists have found evidence that vulnerability to rheumatoid arthritis may begin before birth. Finger joints commonly affected by the disease develop with different tissue structures and larger populations of specialized fibroblasts than joints that are usually spared. Those cells also respond differently to inflammation, suggesting that the architecture of each joint may help determine where arthritis eventually takes hold.

A Developmental Clue to Rheumatoid Arthritis

The findings point to a broader explanation for why rheumatoid arthritis selectively affects particular joints.

Rather than joint vulnerability being determined entirely by immune activity later in life, the tendency for inflammation to develop may also depend on cellular and structural features established while the joints are forming.

In other words, each joint's local biological environment may help determine how susceptible it becomes to rheumatoid arthritis years or decades later.

STUDY

 

[Chandelier]

The embryonic origins of site-specific arthritis, 2026, Davidson et al

Spoiler: Authors

Davidson, Sarah; Simone, Davide; Jansen, Kathrin; Cowan, Max; Machado, Caio; Reekie, Ian; Bhalla, Ananya; Borst, Rowie; Prada Medina, Cesar; Bull, Joshua; Wong, Zhi Yi; Hill, Sarah; Garvilles, Micon; Pledger, Sam; Nisa, Patricia Reis; Schwingen, Nora Rebecca; Windell, Dylan; Attar, Moustafa; Disney, Catherine; Bodey, Andrew J.; Parmenter, Alissa; Byrne, Helen; Ahmed, Sharif; Marathe, Shashidhara; Lee, Peter D.; Mahony, Chris; Croft, Adam P.; Sansom, Stephen; Coles, Mark C.; Buckley, Christopher D.

Abstract
The cellular basis for site-specific inflammation remains unclear. In human fingers, proximal interphalangeal (PIP) joints are preferentially affected by inflammatory arthritis, whereas distal interphalangeal joints are spared, providing a model to investigate the predilection of inflammation to distinct sites.
Here we combine single-cell RNA sequencing, imaging and X-ray tomography to examine cellular composition, spatial organization and structure of finger joints during fetal development.
PIP joints had a larger synovial volume and were enriched for PI16 + ‘universal’ fibroblasts.
These cells were located in perivascular regions and at developing tendon–ligament interfaces. PI16 + fibroblasts exhibited both a shared inflammatory and cell-type-specific response to cytokine stimulation, suggesting that the combination of their spatial location and transcriptional responses promote inflammation.
We suggest that differences in the stoichiometry of mesenchymal cells established in utero, including the key role of PI16 + fibroblasts, is a general principle that drives inflammation susceptibility across tissues.

Web | DOI | PMC | PDF | Nature Immunology | Open Access

 

[Utsikt]

Summary: Scientists have found evidence that vulnerability to rheumatoid arthritis may begin before birth.

That’s a weird way of saying genetics. Unless they are suggesting that something else influence the joints during pregnancy?

 

[Jonathan Edwards]

Chris B seems to have forgotten that we made this point in 1997 and I suspect with much more relevant markers like VCAM-1. It is bizarre that people I worked alongside (I think Chris B took up the chair at Bimingham that I had been offered but politely declined) have forgotten, or maybe never registered, the work that set rituximab in motion. Of course these joints are susceptible because of their stromal cell population behaviour. Talk about Rip van Winkel.