AB0165 A Decreased Frequency of Circulating Follicullar Helper T Cell Counterparts and Plasmablasts in Ankylosing Spondylitis is Restored by TNF Blockers
Authors: M.-B. Bautista-Caro, I. Arroyo-Villa, C. Castillo-Gallego, E. de Miguel, D. Peiteado, C. Plasencia-Rodríguez, A. Villalba, A. Puig-Kröger, E. Martín-Mola, M.-E. Miranda-Carus
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Follicular helper T cells (Tfh), a CD4 T helper subset localized in lymphoid organs, help B cell differentiation and function. Circulating CD4 T cells expressing CXCR5 together with ICOS and/or PD-1 are considered as counterparts of Tfh, can function as B cell helpers, and can be subdivided into three subpopulations based on the expression of CCR6 and/or CXCR3: CXCR5+CXCR3+CCR6- (Tfh-Th1), CXCR5+CXCR3-CCR6+ (Tfh-Th17) and CXCR5+CXCR3-CCR6- (Tfh-Th2). Only Tfh-Th17 and Tfh-Th2, as opposed to Tfh-Th1, seem to display functional properties of Tfh cells. An altered proportion of these subpopulations has been associated with autoimmune diseases. <h3>Objectives</h3> To study the frequency of circulating Tfh and Tfh cell subsets together with the frequency of circulating plasmablasts (CD19+CD20-CD27+CD38high B cells) in patients with Ankylosing Spondilytis (AS). <h3>Methods</h3> Peripheral blood was drawn from healthy controls (n=50), AS patients receiving NSAIDs (n=25) and AS patients treated with TNF blocking agents (n=25). After isolation by Ficoll-Hypaque gradient, PBMCs were stained with antibodies to CD3, CD4, CXCR5, ICOS, PD-1, CCR6, CXCR3, CD19, CD20, CD27, and CD38, and examined by flow cytometry. The percentages of CXCR5+CXCR3+ CCR6- (Tfh-Th1), CXCR5+CXCR3- CCR6+ (Tfh-Th17) and CXCR5+CXCR3-CCR6- (Tfh/Th2) cells were calculated after gating for CD3, CD4 and CXCR5+. The percentage of CD20-CD38high cells was calculated after gating for CD19+ and CD27+. <h3>Results</h3> The frequency of circulating CXCR5+ cells gated for CD4+ T cells was not different among the studied groups. In contrast, AS patients receiving NSAIDs but not those on TNF blockers, demonstrated a decreased frequency of CD4+CXCR5+ICOS+ PD-1+ cells. Furthermore, in AS patients receiving NSAIDs, the frequency of Tfh-Th1 cells was significantly increased and the frequency of Tfh-Th17 and Tfh-Th2 cells was significantly decreased as compared with controls. Subsequently, the ratio (Tfh-Th17+Tfh-Th2)/Tfh-Th1 was decreased in these patients. At the same time, the frequency of circulating plasmablasts was decreased in AS patients on NSAIDs. Interestingly, there was a significantly positive correlation between the percentage of circulating plasmablasts and the frequency of CXCR5+ICOS+PD-1+CD4+ T cells. In addition, the frequency of circulating plasmablasts showed a positive correlation with the ratio (Tfh-Th17+Tfh-Th2)/Tfh-Th1. <h3>Conclusions</h3> AS patients treated with NSAIDS, but not those receiving TNF blockers, demonstrate a decreased frequency of circulating Tfh counterparts (CXCR5+ICOS+PD-1+CD4+ T cells) and altered proportions of circulating Tfh subpopulations, with underrepresentation of subsets bearing a phenotype associated with B cell helping capacity. At the same time, a decreased proportion of circulating plasmablasts is apparent in AS patients treated with NSAIDs. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1753