SAT0033 TCR REPERTOIRE PROFILING OF SYNOVIAL FLUID OF HLA-B*27+ AND HLA-B*27- PATIENTS WITH PSORIATIC ARTHRITIS
Authors: Ekaterina Komech, Anastasia Koltakova, Alena Novikova, Elena Loginova, Tatiana Korotaeva, Ivan Zvyagin
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Diagnosis of psoriatic arthritis (PsA) is primarily based on clinical phenotype because of the diversity of the associated features [1]. The heterogeneity likely implies different mechanisms of the disease progression or initiation. Certain HLA alleles have been shown as risk factors for different spondyloarthropathies (SpAs), implying role of T cells in the pathogenesis. The most prominent association have been shown for HLA-B*27 allele with ankylosing spondylitis (AS), giving raise to the arthritogenic peptide theory of the disease initiation. Recently, using deep TCR profiling, new data supporting potential role of CD8+ T cells in AS have been published by our group and others [2,3]. Despite heterogeneous phenotype 24% of patients from combined cohort of AS and PsA fulfill both CASPAR and modified new-york criteria [4]. Also there is known tendency for axial disease in HLA-B*27+ PsA patients <h3>Objectives:</h3> Here we for the first time applied deep TCR profiling to study T cell repertoire of inflamed joints of patients with PsA, to characterise the similarity in clonal composition between patients in presence and absence of HLA-B*27 <h3>Methods:</h3> We collected paired PB and SF samples from HLA-B*27+ (n=5) and HLA-B*27- (n=7) patients. All patients fulfilled the CASPAR criteria. TCR beta profiling for total P/SFMC samples and T cell subsets was performed using high throughput sequencing of 5'-RACE double-barcoded TCR beta cDNA libraries following by repertoire reconstruction with molecular barcode-based error correction [5] <h3>Results:</h3> Clonal diversity in SF was largely restricted compared to PB, with significant enrichment of mostly expanded SF clonotypes compared to PB, suggesting antigen-driven migration and expansion of the T cells into inflamed site. Major clonal expansions of SF were private for each patient, yet SF shared significantly more clonotypes than PB independently from HLA-B*27 status. Most important, in CD8+ subsets from PB and SF we identified the previously described AS-associated T-cell clonotypes. These clonotypes were detected in SF of all HLA-B*27+ patients but not in samples from HLA-B*27- patients, suggesting the HLA-B*27 restriction of the TCR beta motif. The clonotypes were enriched in SF compared to PB, representing up to 1.6% of CD8+ SF T cells. All HLA-B*27+ patients had several variants of the TCR beta clonotypes in SF, suggesting the selection of the TCRs during disease development <h3>Conclusion:</h3> Our results further support the supposed role of the CD8+ T cells in SpAs and suggest that similarity of clinical phenotype between AS and HLA-B*27+ PsA patients could be associated with autoimmune response to similar antigens, represented by HLA-B*27 molecule <h3>References</h3> [1] Veale D. J. and Fearon U. (2018) 'The pathogenesis of psoriatic arthritis', Lancet (London, England). Elsevier Ltd, 391(10136), pp.2273–84 [2] Faham M. et al. (2016) 'Discovery of T-Cell Receptor Beta Motifs Specific to HLA-B27 + Ankylosing Spondylitis by Deep Repertoire Sequence Analysis', Arthritis &amp; Rheumatology, 11(10), pp.300–8 [3] Komech E. A. et al. (2018) 'CD8+ T cells with characteristic T cell receptor beta motif are detected in blood and expanded in synovial fluid of ankylosing spondylitis patients', Rheumatology (Oxford), 57(6), pp.1097–104 [4] Jadon D. R. et al. (2017) 'Axial Disease in Psoriatic Arthritis study: Defining the clinical and radiographic phenotype of psoriatic spondyloarthritis', Annals of the Rheumatic Diseases, 76(4), pp.701–7 [5] Zvyagin I.V. et al. (2017) 'Tracking T-cell immune reconstitution after TCRαβ/CD19-depleted hematopoietic cells transplantation in children', Leukemia, 31(5), pp.1145-53 <h3>Acknowledgement:</h3> Funding: RSF grant No 17-75-10220 <h3>Disclosure of Interests:</h3> Ekaterina Komech: None declared, Anastasia Koltakova: None declared, Alena Novikova: None declared, Elena Loginova Speakers bureau: Novartis, Celgene Corporation, Biocad, Janssen, AbbVie Inc, Tatiana Korotaeva Speakers bureau: Novartis, Celgene Corporation, AbbVie Inc, Biocad, Janssen, Pfizer, UCB, Lilly, Ivan Zvyagin: None declared