LAUSR

Pleiotropic effects of IL-6 receptor antagonist tocilizumab (TCZ) in rheumatoid arthritis (RA) involve circulating T-cells. Preliminary reports have suggested that TCZ therapy can modulate T cell function and humoral immune responses in RA [1,2]. According to other studies, TCZ had no influence on T-lymphocyte subdifferentiation [3].To assess the effect of 12 months (m) TCZ therapy on T-cell phenotype, and to analyze the association between T-cell subsets and RA activity.36 active RA pts (29F/7M); median age 55[46; 64] years; disease duration 120[72; 1928]m; DAS28 score 6,3[5,7;6,7]; RF+100%, ACCP+ 86% were treated with TCZ (8 mg/kg every 4 weeks) in an open-label study. Immunophenotyping was performed at baseline, 6m and 12m. T-cell subpopulations and key laboratory parameters (CRP, RF, ACCP, MCV, MMP-3) were assessed.At baseline, the absolute counts of T cell subpopulations in RA pts - (CD3+), Th (CD3+CD4+), Tc (CD3+CD8+), NK cells (CD3-CD56+) - were comparable with counts in healthy donors (table1). At baseline, the absolute NK cells (CD3-CD56+) count correlated with MCV (r=0,35, p<0,05) and with MMP-3 (r=0,57, p<0,05) in RA pts. After 6m of TCZ therapy, 34% of pts were classified as good responders, 66% - as moderate responders; after 12m of TCZ therapy 68% of pts - as good responders, 32% - as moderate responders, according to the response criteria of the EULAR. Tc (CD3+CD8+) absolute count reductions were documented after 6m of TCZ therapy, absolute of T cells (CD3+) count and Th (CD3+CD4+) count - after 12m of TCZ therapy (table1). A positive correlation between Tc (CD3+CD8+) absolute counts and RF (r=0,50, p<0,05) was found after 6m of TCZ therapy. A negative correlation of Δ CRP was established with Δ T cells (CD3+) (r=-0,45], Δ Th (CD3+CD4+) (r=-0.47), and Δ Tc (CD3+CD8+) (r=-0,59, p<0,05 in all cases) after 12m of TCZ. The median absolute counts of T cells (CD3+), Th (CD3+CD4+) was lower than on healthy donors after 12m of TCZ therapy. NK cells (CD3-CD56+) counts and Th/Tc index did not change after 12 m of TCZ therapy vs healthy donors and baseline values.Immunophenotyping in pts with active RA showed no difference in the absolute counts of T-cell subpopulations (T cells (CD3+), Th (CD3+CD4+), Tc (CD3+CD8+), NK cells (CD3-CD56+)) compared to healthy donors. T cells (CD3+), Th (CD3+CD4+) and Tc (CD3+CD8+) T cell counts dropped after 6 or 12m of TCZ therapy. Significant correlation between the T-cell subpopulations counts and values of RA laboratory indicators (CRP, MCV, RF, MMP-3) suggest potential T-lymphocytes involvement in RA pathogenesis.[1]Kasama T, Isozaki T, Takahashi R, Miwa Y.Clinical effects of tocilizumab on cytokines and immunological factors in patients with rheumatoid arthritis. Int Immunopharmacol. 2016 Jun;35:301-306. doi: 10.1016/j.intimp.2016.03.016.[2]Schinnerling K, Aguillón JC, Catalán D, Soto L. The role of interleukin-6 signalling and its therapeutic blockage in skewing the T cell balance in rheumatoid arthritis. Clin Exp Immunol. 2017 Jul;189(1):12-20. doi: 10.1111/cei.12966.[3]Schwaneck EC, Renner R, Junker L. et al. T cells, natural killer cells, and gammadeltaT cells in a large patient cohort with rheumatoid arthritis: influence of age and anti-rheumatic therapy. Scand J Rheumatol. 2020 Jan;49(1):8-12. doi: 10.1080/03009742.2019.1634755.Table 1.The effect of tapering tocilizumab on achieving outcomesDonorsBaseline6m12mT cell (CD3+)1,3 (1,2-1,8)∧1,2 (0,9; 1,7)*1,1 (0,7; 1,4)1,0 (0,7; 1,5)* ∧Th (CD3+CD4+)0,9 (0,7-1,2) ∧0,8 (0,6; 1,0)*0,7 (0,5; 1,0)0,6 (0,4; 1,1) * ∧Tc (CD3+CD8+)0,4 (0,3-0,5)0,4 (0,2; 0,5)**0,3 (0,2; 0,04)**0,3 (0,3; 0,5)Тh/Тc2,5 (1,9-3,1)2,3 (1,4; 3,0)2,3 (1,5; 3,6)2,3 (1,4; 4,0)NK (CD3-CD56+)0,2 (0,2-0,5)0,2 (0,1; 0,2)0,2 (0,1; 0,3)0,2 (0,1; 0,3)Note: * - p<0,05 between pts at baseline and after 12 m of TCZ therapy;**- p= 0,02 between pts at baseline and after 6 m of TCZ therapy;∧ - - p<0,05 between donors and pts after 12 m of TCZ therapy.None declared