Association of T-cell receptor β repertoire diversity and frequent exacerbation phenotype in COPD

<bold>Aims:</bold> Exacerbations of COPD negatively impact health status, rates of hospitalization and readmission, and disease progression in patients. The frequent exacerbation phenotype defined by two or more exacerbations in a given year is a distinct subgroup associated with poorer clinical outcomes. Adaptive immune processes have been implicated in the pathogenesis of COPD, and peripheral T-cell dysfunctions are associated with disease severity. We aim to characterize the association between the circulating T-cell receptor (TCR) β repertoire and exacerbation risk or airflow limitation in stable COPD patients. <bold>Methods:</bold> The composition and diversity of peripheral blood TCR β-chain complementarity determining region 3 (CDR3) genes in 25 patients with COPD at stable state and 13 healthy control subjects were investigated using high-throughput sequencing. <bold>Results:</bold> The Shannon and Richness indexes significantly differed between COPD patients and healthy controls. Moreover, the two indices were further decreased in the frequent exacerbators (FE) and the patients with higher mMRC scores (grade 3-4) than infrequent exacerbators (IF) and the patients with lower mMRC scores (grade 1-2), respectively. Potential pathological FE-specific CDR3 motifs were identified. Shannon and Richness indexes are correlated with lung function parameters, including FEV1/FVC, FEV1%pred, MEF50, and MEF25. <bold>Conclusions:</bold> Our study revealed a potential association between TCR repertoire features and the frequent exacerbation phenotype and disease severity in COPD, providing potential immune biomarkers and therapeutic targets for further investigation.