Increased frequency of JC-polyomavirus detection in rheumatoid arthritis patients treated with multiple biologics.

Progressive multifocal leukoencephalopathy (PML) represents a rare but potentially fatal reactivation of JC-polyomavirus (JCPyV) recently also reported in patients with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis (RA) treated with rituximab. The aim of the present study was to analyse the pattern of JCPyV infections in patients with RA undergoing treatment with biologic agents. Urine and blood samples were analysed from 80 patients for antibody levels and/or the presence of JCPyV DNA. Genotyping of the control region and VP1 was performed for all JCPyV DNA-positive specimens. Viremia of JCPyV was only temporarily detected in two patients, and these viruses did not carry any mutations associated with the occurrence of PML. JCPyV DNA was prevalent in initial urine samples of 33% of all patients. RA patients who have consecutively been treated with two or more biologic agents revealed significantly higher prevalence of JCPyV DNA in the urine compared to RA patients treated with their first biologic agent. The presence of JCPyV DNA in the urine closely correlated to JCPyV antibody positivity, and therefore, antibody titres were higher in RA patients who had consecutively received two or more biologic agents over time. Therefore, the overall number of biologic agents had an impact on the pattern of JCPyV detection in this study. Hence, JCPyV antibody screening might be useful as part of the PML risk stratification for RA patients in the future.

Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a) levels in human subjects with rheumatoid diseases.

BACKGROUND: Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has been found to be increased in type 2 diabetic subjects. However, it still remains unclear if these elevated IL-6 levels are co-incidental or if this cytokine is causally related to the development of insulin resistance and type 2 diabetes in humans. Therefore, in the present study we examined insulin sensitivity, serum adipokine levels and lipid parameters in human subjects before and after treatment with the IL-6 receptor antibody Tocilizumab. METHODOLOGY/PRINCIPAL FINDINGS: 11 non-diabetic patients with rheumatoid disease were included in the study. HOMA-IR was calculated and serum levels for leptin, adiponectin, triglycerides, LDL-cholesterol, HDL-cholesterol and lipoprotein (a) (Lp (a)) were measured before as well as one and three months after Tocilizumab treatment. The HOMA index for insulin resistance decreased significantly. While leptin concentrations were not altered by inhibition of IL-6 signalling, adiponectin concentrations significantly increased. Thus the leptin to adiponectin ratio, a novel marker for insulin resistance, exhibited a significant decrease. Serum triglycerides, LDL-cholesterol and HDL-cholesterol tended to be increased whereas Lp (a) levels significantly decreased. CONCLUSIONS/SIGNIFICANCE: Inhibition of IL-6 signalling improves insulin sensitivity in humans with immunological disease suggesting that elevated IL-6 levels in type 2 diabetic subjects might be causally involved in the pathogenesis of insulin resistance. Furthermore, our data indicate that inhibition of IL-6 signalling decreases Lp (a) serum levels, which might reduce the cardiovascular risk of human subjects.