Announced on Apr 12, 2017
The worst-case scenario for people with ankylosing spondylitis (AS) is complete fusion of the spine.
AS is a form of arthritis that primarily affects the joints of the spine for which there is currently no cure. It is characterized by pain, swelling and inflammation. The body adapts to the inflammation by calcifying the soft tissues around the affected joints (ie, turning them into bone). Over time, this process leaves the spine as stiff as a tree trunk, severely limiting mobility.
A particular gene, called the human leukocyte antigen B27 subtype (HLA-B27), is associated with the disease: over 90% of AS patients have HLA-B27. But fewer than 1 in 20 people with the HLA-B27 gene develop AS. Thus, there must be another mechanism involved in disease onset.
HLA-B27 delivers specific molecules, called antigens, to T-cells. T-cells activate the immune system when presented with antigens. Thus, a popular theory is that both HLA-B27 and disease-specific antigens are needed to initiate the chronic immune response observed in AS. But this theory has remained unproven.
A research team led by Krembil Senior Scientist Dr. Robert Inman and Dr. Malek Faham from Adaptive Biotechnologies Corporation recently investigated the possible link between HLA-B27 and the immune system by collecting T-cells from people with and without AS. In studying the cells, the team found 21 features that were unique to T-cells from AS patients with HLA-B27. These results suggest that the T-cells in people with AS are able to receive certain antigens from HLA-B27 that the T-cells in healthy people are not.
These findings advance our understanding of the complex relationship between HLA-B27, the body’s immune system and AS. They suggest that the immune system, triggered by a particular antigen that specifically interacts with HLA-B27, influences the development of AS—findings that may be the first step towards preventing the disease.
This work was supported by Adaptive Biotechnologies Corp., the W. M. Keck Foundation Medical Research Program and the Toronto General & Western Hospital Foundation.
Faham M, Carlton V, Moorhead M, Zheng J, Klinger M, Pepin F, Asbury T, Vignali M, Emerson RO, Robins HS, Ireland J, Baechler-Gillespie E, Inman RD. Discovery of T-Cell Receptor Beta Motifs Specific to HLA-B27+ Ankylosing Spondylitis by Deep Repertoire Sequence Analysis. Arthritis Rheumatol. 2016 Dec 21. doi: 10.1002/art.40028.