Abstract:
: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.
journal_name
Diabetesjournal_title
Diabetesauthors
Viisanen T,Ihantola EL,Näntö-Salonen K,Hyöty H,Nurminen N,Selvenius J,Juutilainen A,Moilanen L,Pihlajamäki J,Veijola R,Toppari J,Knip M,Ilonen J,Kinnunen Tdoi
10.2337/db16-0714subject
Has Abstractpub_date
2017-02-01 00:00:00pages
437-447issue
2eissn
0012-1797issn
1939-327Xpii
db16-0714journal_volume
66pub_type
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