Altered balance between circulating T follicular helper and T peripheral helper cells and regulatory B cells in COPD: an exploratory cross-sectional study

Abstract Background Tertiary lymphoid organs (TLOs) develop in the lungs of patients with chronic obstructive pulmonary disease (COPD) and may contribute to persistent inflammation. CXCL13 is involved in lymphoid follicle organization, but the relationships among circulating T follicular helper (cTfh), T peripheral helper (cTph), regulatory B (cBreg) cells, and CXCL13 in COPD remain unclear. Methods cTfh, cTph, and cBreg cells were analyzed by flow cytometry in 41 patients with COPD, 24 non-COPD smokers, and 13 non-smoking healthy volunteers (HVs). Plasma CXCL13 levels were measured by enzyme-linked immunosorbent assay. Based on the observed immune-cell profiles, exploratory analyses were performed to assess the cPD-1 + ICOS + Tfh/cBreg and cTph/cBreg ratios as candidate markers for distinguishing patients with COPD from non-COPD smokers. Univariable logistic regression and receiver operating characteristic (ROC) analyses were performed. Results The percentage of cTfh cells did not differ significantly among the three groups. Patients with COPD had a significantly higher percentage of cPD-1 + ICOS + Tfh cells and cTph cells than non-smoking HVs, whereas the percentage of cTph cells did not differ significantly between patients with COPD and non-COPD smokers. The percentage of cBreg cells was significantly lower in patients with COPD than in both non-COPD smokers and non-smoking HVs. Plasma CXCL13 levels were significantly higher in patients with COPD than in both control groups. The cPD-1 + ICOS + Tfh/cBreg and cTph/cBreg ratios were significantly higher in patients with COPD than in non-COPD smokers. Exploratory ROC analyses showed moderate discriminatory ability for the cPD-1 + ICOS + Tfh/cBreg ratio, cTph/cBreg ratio, and plasma CXCL13, with AUCs of 0.730, 0.777, and 0.755, respectively. Conclusions Patients with COPD showed reduced cBreg cells, increased cPD-1 + ICOS + Tfh/cBreg and cTph/cBreg ratios, and elevated plasma CXCL13 levels. These findings suggest an altered helper/regulatory immune balance in COPD and support further evaluation of these immune-cell ratios and plasma CXCL13 as candidate immunological markers in independent cohorts.