IL-6 is present in beta and alpha cells in human pancreatic islets: Expression is reduced in subjects with type 1 diabetes.

IL-6 is a pro-inflammatory cytokine upregulated in some autoimmune diseases. The role of IL-6 in the development of type 1 diabetes (T1D) is unclear. Clinical studies are investigating whether tocilizumab (anti-IL-6 receptor) can help preserve beta cell function in patients recently diagnosed with T1D. However, in some rodent models and isolated human islets, IL-6 has been found to have a protective role for beta cells by reducing oxidative stress. Hence, we systematically investigated local tissue expression of IL-6 in human pancreas from non-diabetic, auto-antibody positive donors and donors with T1D and T2D. IL-6 was constitutively expressed by beta and alpha cells regardless of the disease state. However, expression of IL-6 was highly reduced in insulin-deficient islets of donors with T1D, and the expression was then mostly restricted to alpha cells. Our findings suggest that the implication of IL-6 in T1D pathogenesis might be more complex than previously assumed.

Impact of Comorbidity on Physical Function in Patients With Ankylosing Spondylitis and Psoriatic Arthritis Attending Rheumatology Clinics: Results From a Cross-Sectional Study.

OBJECTIVE: To evaluate the impact of comorbidities on physical function in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: This was a cross-sectional analysis of the baseline visit from the Cardiovascular in Rheumatology study. Multivariate models with physical function as the dependent variable (Bath Ankylosing Spondylitis Functional Index and Health Assessment Questionnaire for AS and PsA, respectively) were performed. Independent variables were a proxy for the Charlson Comorbidity Index (CCIp; range 0-27), sociodemographic data, disease activity (erythrocyte sedimentation rate [ESR] and Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] in AS; Disease Activity Score in 28 joints [DAS28] using the ESR in PsA), disease duration, radiographic damage, and treatments. Results were reported as beta coefficients, 95% confidence intervals (95% CIs), and P values. RESULTS: We included 738 patients with AS and 721 with PsA; 21% of patients had >1 comorbidity. Comorbidity burden (CCIp) was independently associated with worse adjusted physical function in patients with PsA (ß = 0.11). Also, female sex (ß = 0.14), disease duration (ß = 0.01), disease activity (DAS28-ESR; ß = 0.19), and the use of nonsteroidal antiinflammatory drugs (ß = 0.09), glucocorticoids (ß = 0.11), and biologics (ß = 0.15) were associated with worse function in patients with PsA. A higher education level was associated with less disability (ß = -0.14). In patients with AS, age (ß = 0.03), disease activity (BASDAI; ß = 0.81), radiographic damage (ß = 0.61), and the use of biologics (ß = 0.51) were independently associated with worse function on multivariate analyses, but CCIp was not. CONCLUSION: The presence of comorbidities in patients with PsA is independently associated with worse physical function. The detection and control of the comorbidities may yield an integral management of the disease.

Lipoprotein(a) concentrations in rheumatoid arthritis on biologic therapy: Results from the CARdiovascular in rheuMAtology study project.

BACKGROUND: Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. OBJECTIVE: The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. METHODS: Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. RESULTS: Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (ß: -0.303, 95% confidence interval: -0.558 to -0.047; P = .02). CONCLUSIONS: RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT.