Plasma Cholinesterase Activity in Patients With Rheumatoid Arthritis and Toxoplasmosis

Background and objective Rheumatoid arthritis (RA) is a chronic autoimmune disease causing synovium inflammation and functional impairment. Toxoplasmosis is an intracellular zoonotic parasitic infection and a risk factor in immunosuppressed diseases including RA. The involvement of the cholinergic mechanism is not clear when both diseases exist in combination. This study aimed to examine plasma cholinesterase (ChE) activity in patients suffering from RA with concomitant toxoplasmosis, taking into account the enzyme susceptibility to in vitro inhibitory challenge with the organophosphate dichlorvos in RA patients. Methods This was a case-control study involving 88 RA patients and 61 healthy controls of both genders. The RA patients were allocated into three groups. The first group received no therapy (n=14), the second group received conventional anti-arthritis therapy (n=49), and the third group received conventional + biologic therapy (n=25). Plasma ChE activity was determined by an electrometric method. Plasma samples were screened for Toxoplasma gondii (T. gondii) infection, using ELISA T. gondii antibodies IgG and IgM. In vitro inhibition of plasma ChE activity was assessed by incubating the samples with dichlorvos at 0.25 and 0.5 μM. The time-dependent dichlorvos (0.25 μM)-induced plasma ChE inhibition and its kinetics were determined. Results The RA patients comprised 76 (86.4%) females and 12 males (13.6%), whereas healthy controls included 22 (36.1%) females and 39 (63.9%) males. The rates of toxoplasmosis IgG positivity in controls and RA patients were 26.2% and 39.8%, respectively. Plasma ChE activity in patients with RA was significantly higher than that in the control group, by 16%. Plasma ChE values of RA patients with conventional therapy and conventional + biologic therapy were higher than that of the control group, by 18% and 27%, respectively. Odds and risk ratios of elevated plasma ChE activity (20%) in RA patients with therapy indicated that high plasma ChE activity among RA patients with therapy is a risk factor. The plasma ChE activity of T. gondii IgG-positive RA patients was not significantly different from that of the IgG-negative ones. Dichlorvos at 0.25 and 0.5 μM significantly inhibited in vitro plasma ChE activity in controls and RA patients. The rates of plasma ChE inhibition by dichlorvos were lower in the RA groups with conventional therapy in comparison with those in the control group (77% vs. 91%). Examining the dichlorvos time-dependent ChE inhibition kinetics, RA groups showed increases in the half-life of inhibition by 23.6% to 32.7% and the total inhibition time by 23.5% to 32.5%, together with decreases in the inhibition rate constant by 19% to 24.5%, an indication of reduced inhibition rate of plasma ChE activity compared to that of the control group. Conclusions The autoimmune nature of RA and its chronicity might have contributed to the increase in plasma ChE activity among the patients. This increase in enzyme activity could be a risk factor in RA patients undergoing conventional therapy alone or in combination with biologic therapy; however, the clinical significance of such a condition remains obscure at present. The in vitro inhibition of plasma ChE activity in RA patients suggests reduced susceptibility of the enzyme to ChE inhibition by dichlorvos. Toxoplasmosis was not a risk factor when plasma ChE activity was taken into account among RA patients.