Background Rheumatoid arthritis (RA) is characterized by abnormal prevalence of Th1, Th2, Th17, and regulatory (Treg) subsets. Some data suggest that these subsets are influenced by anti-RA agents. Biologic therapies target different elements in autoimmune process. These agents are regarded as therapeutically equivalent clinical alternatives in RA. However, there are still some slight differences in their action, individual responses, and side effect profile. Follow-up studies monitoring T cell phenotype in response to biologic therapies are limited. We investigated the alteration of CD4+ and CD8+ T cell subset distribution during long term follow-up of anti-TNF and IL-6 receptor antagonist (IL6ra) therapies.
Methods We enrolled RA patients including 28 anti-TNF responders, 38 IL6ra responders and 19 secondary anti-TNF non responders. Blood was taken at least half year after the initiation of biologic therapies. Ten volunteers served as controls. The T cell phenotype was assessed with flow cytometry.
Results In anti-TNF responders, CD4+ prevalence was lower than in anti-TNF non responders, IL6ra responders and controls (Figure). CD4/CD45RA prevalence was lower in all RA groups than in controls. CD4/CD69 prevalence was higher in IL6ra responders than in anti-TNF responders and anti-TNF non responders. CD4/HLADR prevalence was higher in anti-TNF and IL6ra responders than in controls. CD4/CD25 prevalence was lower in all RA groups than in controls and CD4/CD25 prevalence was higher in IL6ra responders than in anti-TNF responders. In IL6ra responders, Th1 prevalence decreased, while Th2 prevalence increased compared to anti-TNF treated groups and controls; and anti-TNF responders and controls, respectively. Th17 prevalence was higher in all RA groups than in controls and Th17 prevalence was also higher in IL6ra responders compared to anti-TNF treated groups. Treg prevalence normalized in all RA groups (Figure) (1). CD8+ prevalence was lower in IL6ra responders than in anti-TNF treated groups and controls (Figure). CD8/CD45RA and CD8/CD45RO prevalence were lower in all RA groups than in controls. CD8/CD69 prevalence was higher in IL6ra responders than in anti-TNF treated groups and controls. CD8/HLADR prevalence was higher in anti-TNF responders than in controls.
Conclusions Biological therapies exhibit marked effects on all the cell populations investigated; some significant differences in this action exist between anti-TNF and IL6ra therapies. This study on peripheral blood samples has provided comprehensive information regarding the long term impact of biologic therapies on CD4+and CD8+ cell distributions.
Szalay B, Vásárhelyi B, Cseh Ά, Tulassay T, Deák M, Kovács L, Balog A. The impact of conventional DMARD and biological therapies on CD4+ cell subsets in rheumatoid arthritis: a follow-up study. Clin Rheumatol 2014. 33:175–85.
Disclosure of Interest None declared