Background/Purpose: Relapsing polychondritis (RP) is a rare, systemic inflammatory disease characterized by recurrent inflammation of cartilaginous structures, including the nose/ears, joints, and trachea. The etiology of this life-threatening and disabling disease is currently unknown and little is known about its pathogenesis. HLA association evidence supports T-cell involvement in RP; however, the extent of T-cell involvement is incompletely understood. Previous studies demonstrate that TCR repertoire diversity is decreased in individuals with autoimmune diseases, such as rheumatoid arthritis and type 1 diabetes. Here we study the TCR repertoire of individuals with RP to identify potential disease-causing clones, which may provide critical knowledge in uncovering disease etiology, serve as a biomarker, or influence treatment decisions.

Methods: Peripheral blood leukocyte DNA was collected from 13 patients with highly active RP, and TCR-β chains were sequenced by Adaptive Biotechnologies. 3 samples containing a dominant clone were re-sequenced at a time of reduced disease activity. 13 age and sex matched healthy controls were obtained from the ImmuneACCESS public database. Data was analyzed using ImmunoSEQ Analyzer to quantify Productive Entropy, Max Productive Frequencies, Differential Abundance, and TCR- β chain V family gene usage. Frequencies were compared using the Mann-Whitney U test. Physician global assessment (PGA) was used to determine disease activity in a subset of the patients.

Results: Productive Entropy values were significantly lower in patients with RP compared to healthy controls (median 15.73 vs 16.86, P=0.0015), indicating a less diverse TCR repertoire in patients with RP. 3 patients had unique dominant clones with Max Productive Frequencies over 5 % (range 5.68-10.71%). In 2 of these patients Productive Entropy values increased in parallel with improvement in PGA scores (12.316 to 12.8916 and 14.1600 to 15.5207 respectively) and Max Productive Frequencies of dominate clones decreased (5.675% to 4.961% and 10.712% to 7.476% respectively). Additionally, 3 TCR- β chain variable (V) expansions were detected for Vβ9, Vβ19, and Vβ20 families that were not expanded in controls.

Conclusion: TCR repertoire is less diverse in patients with RP compared to healthy controls. Expanded TCR- β chain V families and dominant clones not expressed in healthy controls may provide insights to antigenic drivers of RP. Further, the TCR repertoire may be less diverse during active disease compared to lower disease activity. Based upon these findings, we intend to confirm the trends in a larger cohort of patients, make comparisons to immunophenotypes and clinical associations, and detect possible antigens by clustering TCRs with conserved CDR3 and V family motifs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/t-cell-receptor-tcr-sequencing-reveals-decreased-diversity-and-clonotypic-expansion-of-t-cells-in-relapsing-polychondritis-rp/