title: Decreased frequencies of circulating follicular helper T cell counterparts and plasmablasts in ankylosing spondylitis patients Naïve for TNF blockers.
abstract: Follicular helper T cells (Tfh), localized in lymphoid organs, promote B cell differentiation and function. Circulating CD4 T cells expressing CXCR5, ICOS and/or PD-1 are counterparts of Tfh. Three subpopulations of circulating CD4+CXCR5+ cells have been described: CXCR3+CCR6- (Tfh-Th1), CXCR3-CCR6+ (Tfh-Th17), and CXCR3-CCR6- (Tfh-Th2). Only Tfh-Th17 and Tfh-Th2 function as B cell helpers. Our objective was to study the frequencies of circulating Tfh (cTfh), cTfh subsets and plasmablasts (CD19+CD20-CD27+CD38high cells), and the function of cTfh cells, in patients with Ankylosing Spondylitis (AS). To this end, peripheral blood was drawn from healthy controls (HC) (n = 50), AS patients naïve for TNF blockers (AS/nb) (n = 25) and AS patients treated with TNF blockers (AS/b) (n = 25). The frequencies of cTfh and plasmablasts were determined by flow cytometry. Cocultures of magnetically sorted CD4+CXCR5+ T cells with autologous CD19+CD27- naïve B cells were established from 3 AS/nb patients and 3 HC, and concentrations of IgG, A and M were measured in supernatants. We obseved that AS/nb but not AS/b patients, demonstrated decreased frequencies of circulating CD4+CXCR5+ICOS+PD-1+ cells and plasmablasts, together with a decreased (Tfh-Th17+Tfh-Th2)/Tfh-Th1 ratio. The amounts of IgG and IgA produced in cocultures of CD4+CXCR5+ T cells with CD19+CD27- B cells of AS/nb patients were significantly lower than observed in cocultures established from HC. In summary, AS/nb but not AS/b patients, demonstrate a decreased frequency of cTfh and plasmablasts, and an underrepresentation of cTfh subsets bearing a B helper phenotype. In addition, peripheral blood CD4+CXCR5+ T cells of AS/nb patients showed a decreased capacity to help B cells ex vivo.
authors.affiliation: Department of Rheumatology, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: María-Belén
authors.initials: MB
authors.lastname: Bautista-Caro
authors.affiliation: Department of Rheumatology, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Arroyo-Villa
authors.affiliation: Department of Rheumatology, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Castillo-Gallego
authors.affiliation: Department of Rheumatology, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: de Miguel
authors.affiliation: Department of Rheumatology, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Peiteado
authors.affiliation: Department of Rheumatology, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: Chamaida
authors.initials: C
authors.lastname: Plasencia-Rodríguez
authors.affiliation: Department of Rheumatology, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Villalba
authors.affiliation: Laboratorio de Inmuno-Oncología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Sánchez-Mateos
authors.affiliation: Laboratorio de Inmuno-Oncología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Amaya
authors.initials: A
authors.lastname: Puig-Kröger
authors.affiliation: Department of Rheumatology, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Martín-Mola
authors.affiliation: Department of Rheumatology, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: María-Eugenia
authors.initials: ME
authors.lastname: Miranda-Carús
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology*; D054380:Receptors, CXCR5 / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D054380:Receptors, CXCR5