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Hello, my name is Atul Devdar. I'm a professor of medicine at Oregon Health and Science University in Portland, Oregon.
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And I am at the RheumNow desk at the ACR 2026 meeting.
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I wanted to talk today about the changing trends of management in axial spondyloarthritis.
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We have been treating patients with axial spondyloarthritis of course with physical therapy, non-steroids, and cytokine-based therapies.
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More recently, people are now getting interested in cell-based therapies for axial spondyloarthritis, and we are concentrating on the CD8-positive T-cells, and also the interaction
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between HLA-B27 molecule, which is an MHC class 1 molecule presenting an arthritogenic peptide, which was the original theory, to a CD8-positive T-cell.
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It has been found that there is a possibility that this so-called arthritogenic peptide could be a peptide coming from the gut.
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A small peptide is sitting into that HLA-B27 groove, recognized by the CD8-positive T-cell receptor.
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And if you think about the T-cell receptor, it has got the alpha chain and the beta chain and the CDR3 part — that is the complementarity-determining region three.
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Those are the molecules which interact with this particular peptide sitting in the HLA-B27 groove.
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It has been found that patients who develop spondyloarthritis somehow have their HLA-B27 presenting a small peptide probably received from the gut, and then the
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CD8-positive T-cells which actually have TRBV9 — the beta chain of this T-cell receptor — and the motif is TRBV9, they expand, and that particular
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clonotype expansion leads to development of axial spondyloarthritis.
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Interestingly, this has not only been found in the Caucasian population, but the same TRBV9 expansion has also been found in HLA-B27-positive axial spondyloarthritis patients in China.
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So it has been shown across different types of populations.
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It was then found out that TRAV21 — the alpha chain V21 — so this particular motif of TRBV9 and TRAV21 is even more specific.
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There are companies now which are developing antibodies to kill the TRBV9-positive T-cells or TRAV21-positive T-cells.
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To go even further, there are experiments being done to reduce expansion — or rather expression — of HLA-B27 on the antigen-presenting cell, to dislodge the peptide that they are presenting to the TRBV9-positive T-cells, or even to change or block one of the molecular steps involved.
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One of these is the endoplasmic reticulum — a molecular scissors, if you will — an aminopeptidase.
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It's an endoplasmic reticulum aminopeptidase; it actually chops the peptide into the correct size to fit into the HLA-B27 groove.
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And people are developing ERAP1 and ERAP2 blocking drugs.
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So going forward, the therapy of axial spondyloarthritis is moving away from cytokine-based therapies to cell-based therapies targeting the CD8-positive T-cells which carry the TRBV9 and TRAV21 motif, and in the even further future we will in fact be targeting the antigen-presenting cell itself.
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