Polarization of circulating Follicular Helper T cells correlates with the severity of Bullous Pemphigoid.

Abstract

BACKGROUND T-follicular-helper (Tfh) cells form a distinct population of T-helper cells with different polarizations (type 1, type 2 and type 17) that regulates humoral responses and may participate in the pathophysiology of B-cell mediated autoimmune diseases, such as bullous pemphigoid (BP), a dermatosis mediated by auto-antibodies specific for hemidesmosomal proteins. OBJECTIVES The aim was to evaluate the impact of superpotent topical corticosteroid (TCS) treatment, which is more effective and safer than high doses of oral corticosteroids and recommended first-line treatment of BP, on circulating Tfh cells. METHODS We compared by flow cytometry the frequency, polarization and activation of blood Tfh cells from patients with BP at baseline and longitudinally after initiation of TCS treatment to age- and sex-matched healthy subjects. RESULTS We observed that circulating Tfh cells were more frequent in patients with BP at baseline than in healthy subjects and exhibited an activated phenotype. We further showed a decrease of type 1 and an increase of type 17 Tfh cells in the blood of patients, which resulted in a higher (type 2+type 17) to type 1 Tfh cell ratio. This ratio correlated positively with disease severity as measured by the Bullous Pemphigoid Disease Area Index. Remarkably, along TCS treatment, although the frequency of Tfh cells returned to a level similar to control, the activated phenotype persisted. Interestingly serum IL-21 levels and the Tfh cell subset ratio, similarly to disease activity and serum anti-BP180 and anti-BP230 auto-antibodies, were decreased under the TCS treatment. CONCLUSIONS Overall, our findings suggest an involvement of the polarization of Tfh cells in the pathophysiology of BP and open the door to a modulation of their activity for therapeutic purposes.