Longitudinal TCR repertoires in ulcerative colitis patients show features distinguishing disease states.

BACKGROUND

Ulcerative colitis (UC) affects an estimated 10 million people worldwide. The exact etiology of the disease is unknown, but T-cell dysregulation and aberrant activation is associated with UC-prompting research into T-cell receptor (TCR) repertoires in UC patients. However, few studies have compared UC patient TCR repertoires in flare (inflamed) and remission (uninflamed) states. Moreover, this is the first dataset to our knowledge examining multiple repertoires from UC patients over time, enabling longitudinal analyses.

METHODS

The T-cell receptor repertoires were obtained for 21 patients across multiple timepoints, yielding a total of 58 samples. Repertoire clonality, diversity, overlap, and gene usage frequencies were compared across all patients. Complementarity-determining region CDR3 sequences were split into K-mers (sequences of length K), and enriched K-mers in flare and remission states were identified using turboGliph.

RESULTS

Although repertoires vary across patients, there were significant differences in the usage of 20 Vβ genes across flare and remission states. Moreover, calculation of the overlap in repertoires with enriched K-mers showed higher overlap scores than when using full TCR sequences. We identified 622 unique enriched K-mers in flare states and 495 in remission states, with only 57 overlapping between the 2 states.

CONCLUSIONS

Overall, these results highlight the importance of analyzing Vβ gene usage and K-mer enrichment in TCR repertoires, particularly given the lack of public clones across patient cohorts. Future studies characterizing the specific antigenic targets associated with these features will pave the way for biomarker discovery in UC.