Definition of B cell helper T cells in rheumatoid arthritis and their behavior during treatment

Immunopathogenesis of rheumatoid arthritis (RA) is not yet clearly defined. Besides known B-cell involvement, RA development and evolution involves CD4⁺ T helper cell homeostasis dysregulation. Imbalance between Th17 cells and regulatory T cells have been reported and may contribute to sustained inflammation. Since the last decade, increasing reports focused on a newly described CD4⁺ T helper cell subset, called T follicular helper (Tfh) cells, functionally distinct from other subsets due to their own property to provide help to B cells by enhancing their survival and differentiation into long-lasting antibody secreting cells. More recently, another B cell helper subset, named T peripheral helper (Tph) cells, has been specifically described in synovial tissues and blood of RA patients.

We conducted an exhaustive and careful literature search focusing our interest on T cells specialized on B cell help, Tfh cells and Tph cells, in RA pathogenesis and focused on their modulation during treatments.

Tfh cells and in higher proportions Tph cells were described in synovial tissue and liquid of RA patients. In blood of RA patients, despite the use of diverse Tfh cell definitions, a vast majority of reports revealed an increase of circulating Tph and Tfh cell frequency, compared to healthy controls. However, discordant correlations between disease activity score and either effector or activated circulating Tfh cell subsets were highlighted, probably due to heterogeneity of cohort design in term of definition of disease activity, cohort size and use of different treatments. Indeed, frequencies of circulating Tfh and Tph cells are modulated depending on the nature and duration of RA treatment. Interestingly, it has been demonstrated that the proportion of ICOS-expressing blood Tfh cells before abatacept initiation was an independent and significant predictor of DAS28-ESR improvement at week 24. This report may encourage to conduct further investigations based on T-cell subsets as predictive biomarkers of response to biotherapies.

Mounting evidences hypothesize that circulating Tfh and Tph cells may be involved in RA pathogenesis and response to treatment.