Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Increased T Cell Receptor Clonotype Sharing Among Ankylosing Spondylitis Patients Revealed by Deep Repertoire Sequence Analysis.
Faham1, Malek, Carlton1, Victoria, Moorhead1, Martin, Zheng1, Jianbiao, Asbury1, Tom, Inman2, R. D.
Of all rheumatic diseases, ankylosing spondylitis (AS) exhibits the strongest HLA association, with over 90% of AS patients carrying the class I MHC allele HLA B27. Since the canonical role for class I MHC is peptide presentation to T cells, the HLA-B27 relationship in AS has implicated a T cell response restricted by this antigen presentation function. By implication, this has also suggested that a specific antigen is important in the pathogenesis of the disease. This hypothesis would predict that specific T Cell Receptor (TCR) sequences would be shared among different AS patients.
We have developed a technology for large scale sequencing of TCRb to assess the repertoire profile in individual samples. All TCRb sequences are amplified from peripheral blood samples and >1 million TCRb sequences are obtained to generate a comprehensive profile of the blood TCR repertoire at that time point. We have applied this new technology to determine whether AS patients have excess sharing of TCR sequences.
We assessed TCRb repertoire data obtained from blood samples of 16 individual AS patients, all of whom met the modified New York criteria for AS. This profile was compared with 16 patients with systemic lupus erythematosus (SLE), representative of another autoimmune disease with much lower HLA association. We counted clonotypes that are shared among each patient set (present in >7/16 patients) and found a significantly higher number of shared clonotypes among AS patients (p= 5 = 10-4). Many of the shared clonotypes can be anticipated to be shared by chance, due to the small number of added bases in these clonotypes during the recombination to form the specific TCRb sequence. Therefore we used a TCRb repertoire data from 50 blood samples from 21 healthy individuals to filter out clonotypes that seem to be present in an appreciable number of these samples. We filtered clonotypes present in more than 3 of the normal samples to identify a shared specific clonotypes for each of the SLE and AS patients. We observed a significantly higher number of shared non-generic clonotypes among AS when compared to lupus patients (p= 1.0 = 10-4). A number of these clones, present in 9/16 AS patients, seem highly specific as they were not present in another set of 50 unrelated individuals.
Using a novel deep repertoire sequence analysis, we provide evidence that there is a distinctive set of shared clonotypes in the T cell repertoire in AS patients. This sheds light on the immunological role of HLA B27 in AS, and lays the groundwork for defining the antigenic stimulus for this T cell response, as well as the application of TCR profiling in the diagnosis and clinical assessment of AS.
To cite this abstract, please use the following information:
Faham, Malek, Carlton, Victoria, Moorhead, Martin, Zheng, Jianbiao, Asbury, Tom, Inman, R. D.; Increased T Cell Receptor Clonotype Sharing Among Ankylosing Spondylitis Patients Revealed by Deep Repertoire Sequence Analysis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1339