Rheumatoid arthritis (RA) is a systemic, autoimmune disease characterized by joint involvement, with progressive cartilage and bone destruction. Genetic and environmental factors determine RA susceptibility. In recent years, an increasing number of studies suggested that diet has a central role in disease risk and progression. Several nutrients, such as polyunsaturated fatty acids, present anti-inflammatory and antioxidant properties, featuring a protective role for RA development, while others such as red meat and salt have a harmful effect. Gut microbiota alteration and body composition modifications are indirect mechanisms of how diet influences RA onset and progression. Possible protective effects of some dietary patterns and supplements, such as the Mediterranean Diet (MD), vitamin D and probiotics, could be a possible future adjunctive therapy to standard RA treatment. Therefore, a healthy lifestyle and nutrition have to be encouraged in patients with RA.

Mucosal surfaces play a central role in the pathogenesis of rheumatoid arthritis (RA). Several risk factors, such as cigarette smoking, environmental pollution, and periodontitis interact with the host at the mucosal level, triggering immune system activation. Moreover, the alteration of microbiota homeostasis is gaining increased attention for its involvement in the disease pathogenesis, modulating the immune cell response at a local and subsequently at a systemic level. Currently, the onset of the clinical manifest arthritis is thought to be the last step of a series of pathogenic events lasting years. The positivity for anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), in absence of symptoms, characterizes a preclinical phase of RA—namely systemic autoimmune phase- which is at high risk for disease progression. Several immune abnormalities, such as local ACPA production, increased T cell polarization towards a pro-inflammatory phenotype, and innate immune cell activation can be documented in at-risk subjects. Many of these abnormalities are direct consequences of the interaction between the environment and the host, which takes place at the mucosal level. The purpose of this review is to describe the humoral and cellular immune abnormalities detected in subjects at risk of RA, highlighting their origin from the mucosa–environment interaction.

Endothelial dysfunction has been detected in RA patients and seems to be reversed by control of inflammation. Low circulating endothelial progenitor cells (EPCs) have been described in many conditions associated with increased cardiovascular risk, including RA. The aim of this study was to investigate the effect of inhibition of TNF on EPCs in RA patients. Seventeen patients with moderate-severe RA and 12 sex and age-matched controls were evaluated. Endothelial biomarkers were tested at baseline and after 3 months. EPCs were identified from peripheral blood mononuclear cells by cytofluorimetry using anti-CD34 and anti-vascular endothelial growth factor-receptor 2. Asymmetric dimethylarginine (ADMA) was tested by ELISA and flow-mediated dilatation (FMD) by ultrasonography. Circulating EPCs were significantly lower in RA patients than in controls (P=0.001). After 3 months EPCs increased significantly (P=0.0006) while ADMA levels significantly decreased (P=0.001). An inverse correlation between mean increase in EPCs number and mean decrease of DAS28 after treatment was observed (r=−0.56,P=0.04). EPCs inversely correlated with ADMA (r=−0.41,P=0.022). No improvement of FMD was detected. Short-term treatment with anti-TNF was able to increase circulating EPCs concurrently with a proportional decrease of disease activity suggesting that therapeutic intervention aimed at suppressing the inflammatory process might positively affect the endothelial function.

Systemic rheumatic diseases have significant morbidity and mortality, due in large part to concurrent infections. The lung has been reported among the most frequent sites of infection in patients with rheumatic disease, who are susceptible to developing pneumonia sustained both by common pathogens and by opportunistic microorganisms. Patients with rheumatic disease show a peculiar vulnerability to infectious complications. This is due in part to intrinsic disease-related immune dysregulation and in part to the immunosuppressive treatments. Several therapeutic agents have been associated to a wide spectrum of infections, complicating the management of rheumatic diseases. This review discusses the most frequent pulmonary infections encountered in rheumatic diseases, focusing on opportunistic agents, consequent diagnostic challenges and appropriate therapeutic strategies.

Cardiovascular disease is the main cause of morbidity and mortality in rheumatoid arthritis (RA). Despite the advent on new drugs targeting the articular manifestations, the burden of cardiovascular disease is still an unmet need in the management of RA. The pathophysiology of accelerated atherosclerosis associated to RA is not yet fully understood, and reliable and specific markers of early cardiovascular involvement are still lacking. Asymmetric dimethylarginine is gaining attention for its implication in the pathogenesis of endothelial dysfunction and as biomarkers of subclinical atherosclerosis. Moreover, the metabolic pathway of methylarginines offers possible targets for therapeutic interventions to decrease the cardiovascular risk. The purpose of this review is to describe the main causes of increased methylarginine levels in RA, their implication in accelerated atherosclerosis, the possible role as biomarkers of cardiovascular risk, and finally the available data on current pharmacological treatment.

Full Papers; Authors: C. Iannuccelli, B. Lucchino, C. Gioia, G. Dolcini, M. Favretti, D. Franculli, M. Di Franco