Figure 3

Transmembrane (tm)TNF reverse signaling (RS)-induced secretion of soluble IL1-RI and IL1-RII depends on apoptotic rates and influences clinical response. (A, B) tmTNF RS-induced IL-1RI and IL-1RII expression was measured in in vitro monocyte cultures from rheumatoid arthritis (RA) patients after baseline incubation IgG and TNFR2:Ig for 16 hours. Individually paired data of IL1sRI (A) and IL1sRII (B) concentrations in control cultures (IgG) (solid circles) and in cultures with TNFR2:Ig (solid triangles) determined in vitro at baseline in monocytes from the subgroup of RA patients (n = 10) characterized by high rates of spontaneous in vitro apoptosis (SIA) are as indicated. Significant differences are indicated. (C) Levels of tmTNF RS-induced IL-1RI production (ΔIL-1sRI) by RA monocytes at baseline correlates with spontaneous monocyte apoptosis in these RA patients. Dot plots depicts rate of SIA in relation to the baseline concentration of tmTNF RS-induced IL1sRI (n = 18). ∆IL-1sRI is the difference of tmTNF RS-induced IL-1sRI production and spontaneous IL-1sRI production. Regression coefficient and significane level for linear regression are indicated. (D) Levels of baseline tmTNF RS-induced IL-1RII production by RA monocytes correlated negatively with change (Δ) in disease activity score (DAS)28 12 weeks after starting treatment. Dot plots depicts numeric improvement in (ΔDAS28) in RA patients (n = 18) after 12 weeks of TNF blockade in relation to the concentration of tmTNF RS-induced IL1-sRII (ΔIL-1sRII) at baseline. ∆IL-1sRII is the difference in tmTNF RS-induced IL-1sRII production and spontaneous IL-1sRII production. Regression coefficient and level of significance for the linear regression are as indicated.