A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Circulating CXCR5(+)PD-1(+)ICOS(+) Follicular T Helper Cells Are Increased Close to the Diagnosis of Type 1 Diabetes in Children With Multiple Autoantibodies
Tekijät: Viisanen T, Ihantola EL, Nanto-Salonen K, Hyoty H, Nurminen N, Selvenius J, Juutilainen A, Moilanen L, Pihlajamaki J, Veijola R, Toppari J, Knip M, Ilonen J, Kinnunen T
Kustantaja: AMER DIABETES ASSOC
Julkaisuvuosi: 2017
Journal: Diabetes
Tietokannassa oleva lehden nimi: DIABETES
Lehden akronyymi: DIABETES
Vuosikerta: 66
Numero: 2
Aloitussivu: 437
Lopetussivu: 447
Sivujen määrä: 11
ISSN: 0012-1797
eISSN: 1939-327X
DOI: https://doi.org/10.2337/db16-0714
Tiivistelmä
Although type 1 diabetes (T1D) is primarily perceived as a T cell-driven autoimmune disease, islet autoantibodies are the best currently available biomarker for autoimmunity and disease risk. These antibodies are produced by autoreactive B cells, the activation of which is largely dependent on the function of CD4(+)CXCR5(+) follicular T helper cells (Tfh). In this study, we have comprehensively characterized the Tfh- as well as B-cell compartments in a large cohort of children with newly diagnosed T1D or at different stages of preclinical T1D. We demonstrate that the frequency of CXCR5(+)PD-1(+)ICOS(+)-activated circulating Tfh cells is increased both in children with newly diagnosed T1D and in autoantibody-positive at-risk children with impaired glucose tolerance. Interestingly, this increase was only evident in children positive for two or more biochemical autoantibodies. No alterations in the circulating B-cell compartment were observed in children with either prediabetes or diabetes. Our results demonstrate that Tfh activation is detectable in the peripheral blood close to the presentation of clinical T1D but only in a subgroup of children identifiable by positivity for multiple autoantibodies. These findings suggest a role for Tfh cells in the pathogenesis of human T1D and carry important implications for targeting Tfh cells and/or B cells therapeutically.
Although type 1 diabetes (T1D) is primarily perceived as a T cell-driven autoimmune disease, islet autoantibodies are the best currently available biomarker for autoimmunity and disease risk. These antibodies are produced by autoreactive B cells, the activation of which is largely dependent on the function of CD4(+)CXCR5(+) follicular T helper cells (Tfh). In this study, we have comprehensively characterized the Tfh- as well as B-cell compartments in a large cohort of children with newly diagnosed T1D or at different stages of preclinical T1D. We demonstrate that the frequency of CXCR5(+)PD-1(+)ICOS(+)-activated circulating Tfh cells is increased both in children with newly diagnosed T1D and in autoantibody-positive at-risk children with impaired glucose tolerance. Interestingly, this increase was only evident in children positive for two or more biochemical autoantibodies. No alterations in the circulating B-cell compartment were observed in children with either prediabetes or diabetes. Our results demonstrate that Tfh activation is detectable in the peripheral blood close to the presentation of clinical T1D but only in a subgroup of children identifiable by positivity for multiple autoantibodies. These findings suggest a role for Tfh cells in the pathogenesis of human T1D and carry important implications for targeting Tfh cells and/or B cells therapeutically.
Turun yliopiston Tutkimustietojärjestelmän portaali