Phenotypic characteristics of peripheral blood effector follicular helper T cell subsets in patients with rheumatoid arthritis of different disease activity and their relationship with treatment responsiveness

WANG Nian; BAI Lin

doi:10.3969/j.issn.2095-252X.2026.02.007

Abstract：Objective To explore the phenotypic characteristics and mechanisms of peripheral blood effector follicular helper T cells(Tfh)and their subtypes in patients with rheumatoid arthritis(RA)of different disease activity levels,and determine their relationship with RA treatment responsiveness.Methods 126 RA patients admitted to our hospital from January 2021 to September 2023 were selected and divided into high activity group(n=42),medium activity group(n=39),and low activity group(n=45)based on disease activity.The levels of Tfh cells and their subtypes were compared between the two groups,and LOWESS regression analysis was used to investigate the correlation between Tfh and disease activity.Subsequently,patients were divided into a good response group(n=62)and a non response group(n=64)based on treatment responsiveness.The relationship between Tfh and their subtypes and treatment responsiveness was evaluated using a multi factor generalized linear mixed effects model,and their interaction with disease activity was analyzed.Using a restricted cubic spline model to analyze the relationship between Tfh and subtype levels and patient recurrence risk.Results Statistically significant differences were observed in Tfh(F=117.316,P<0.001),Tfh1(F=172.140,P<0.001),Tfh2(F=272.480,P<0.001)and Tfh17(F=20.228,P<0.001)among three groups.The LOWESS analysis results showed that the levels of Tfh,Tfh2,and Tfh17 were negatively correlated with DAS28 scores,while the level of Tfh1 was positively correlated with disease activity scores.Statistically significant differences were observed in Tfh(t=26.812,P<0.001),Tfh1(t=10.836,P<0.001),Tfh2(t=7.908,P<0.001)and Tfh17(t=3.397,P=0.001)between the two groups.The multi factor generalized linear mixed effects model showed that Tfh,Tfh2,and Tfh17 were negatively correlated with treatment non response(OR<1,P<0.05),while Tfh1 was positively correlated with treatment non response(OR>1,P<0.05).After adjusting for confounding factors,the correlation between Tfh,Tfh1,Tfh2,Tfh17 and treatment responsiveness still existed.In different disease activity groups,the Tfh,Tfh2,and Tfh17 of the non responsive subgroup patients were lower than those of the well responsive subgroup patients,and Tfh1 was higher than that of the well responsive subgroup patients.Tfh,Tfh1,Tfh2,Tfh17 had an interaction with disease activity,with Tfh,Tfh2,Tfh17 showing a negative interaction with high activity,and Tfh1 showing a positive interaction with high activity.The results of the restricted cubic spline model showed a non-linear dose-response relationship between Tfh,Tfh1,Tfh2,Tfh17 and prognostic risk(non-linear detection,P<0.001).As Tfh,Tfh1,Tfh2,Tfh17 increased,prognostic risk decreased;and as Tfh1 increased,prognostic risk increased.Conclusions The peripheral blood Tfh cells and their subtypes(Tfh1,Tfh2,Tfh17)are closely related to the disease activity and treatment responsiveness of RA.Tfh1 levels are positively correlated with disease activity and indicate no response to treatment and poor prognosis,while Tfh2 and Tfh17 may have protective effects.Clinical recommendations include dynamic monitoring of Tfh subgroups to optimize individualized treatment strategies.