Asthma phenotyping through CD26, CD126 and LRRC32 biomarkers: a prospective study

Abstract

The role of effector TH cells (Teff; CD25 low CD127 high ) like TH17 lymphocytes in asthma depends on their interplay with regulatory T cells (Treg; CD25 high CD127 low ), which display low levels of CD26 (TH17>>TH1>TH2>>Treg) but high of LRRC32. The Treg-TH17 balance is controlled by IL-6R, an asthma risk locus together with LRRC32. Our aim was to analyse the levels of CD26, CD126, CD127 and LRRC32 in different lymphocyte subsets during non-active stages of allergic (AA)/non-allergic asthma (NAA) and rhinitis (R). Blood/serum samples were obtained from 268 Spanish adults constituted by 32 healthy donors (HC) and 236 patients (43 R, 103 AA, 90 NAA), and surface markers were assessed by flow cytometry. Our results show that Treg percentage is higher in men, but Treg and Teff numbers remain unchanged in patients (AA, NAA, AR) compared to HC. As expected, AA and NAA have higher mean number of CD26 molecules on CD4 + T cells than HC. Moreover, CD26 (and LRRC32) mean fluorescence intensity within the Treg subset allows to differentiate NAA from AA patients. An expansion of a CD25 low CD26 low CD127 low (triple low; TL) TH subset is detected in AA patients, what is inversely related to CD26 levels and is in line with a reduction of soluble CD26. CD26 (%) and CD126 (%) display a strong positive correlation in TL lymphocytes, and CD26 (%) is decreased in NAA patients compared to AA, AR and HC donors; similar results are obtained for CD26 and CD126 in CD4 − lymphocytes. The % of CD127 + cells in Teff, TL and especially Tregs is increased in patients (AA, NAA, AR) compared to HC. In conclusion, our results open a way to differentiate different phenotypes of asthma according to different levels of T cell surface markers.