The p38 mitogen‐activated protein kinase cascade modulates T helper type 17 differentiation and functionality in multiple sclerosis

The p38 mitogen‐activated protein kinase cascade is required for the induction of a T helper type 17 (Th17) ‐mediated autoimmune response, which underlies the development and progression of several autoimmune diseases, such as experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis (MS). However, the contribution of p38 phosphorylation to human Th cell differentiation has not been clarified. Here we demonstrate that the p38 signalling pathway is implicated in the generation of Th17 lymphocytes from human CD4⁺ CD27⁺ CD45RA⁺ naive T cells, both in healthy donors and in patients affected by the relapsing–remitting form of MS. Our data also indicate that p38 activation is essential for interleukin‐17 release from central memory lymphocytes and committed Th17 cell clones. Furthermore, CD4⁺ T cells isolated from individuals with relapsing–remitting MS display an altered responsiveness of the p38 cascade, resulting in increased p38 phosphorylation upon stimulation. These findings suggest that the p38 signalling pathway, by modulating the Th17 differentiation and response, is involved in the pathogenesis of MS, and open new perspectives for the use of p38 inhibitors in the treatment of Th17‐mediated autoimmune diseases.     

Reduction of fat free mass index and phase angle is a risk factor for development digital ulcers in systemic sclerosis patients

Clinical Rheumatology - This study aims to evaluate the role of fat free mass index (FFMI) and phase angle (PhA) as markers to predict occurrence of new digital ulcers in systemic sclerosis (SSc)...     

Risk of thyroid nodules in subjects occupationally exposed to radiation: a cross sectional study.

OBJECTIVES--To examine, by ultrasonography the prevalence of thyroid nodules in a cross sectional study of male medical workers occupationally exposed to chi radiation at the Pisa hospital, in comparison with controls matched for age and sex. METHODS--50 male medical workers exposed to radiation were randomly matched for age (+/- 2 years) with 100 male workers not occupationally exposed to ionising radiation who lived in a slightly iodine deficient area of Tuscany (Lunigiana) (control group 1), and with 100 male workers not exposed to radiation who lived in the same area (Pisa) (control group 2). RESULTS--Of the occupationally exposed subjects, thyroid nodules were detected in 19/50 (38.0%). Among controls, thyroid nodules were detected in 19/100 subjects of control group 1 and in 13/100 of control group 2. Comparison of exposed and control groups, stratified into 30-39, 40-49, and 50-59 year old age subgroups, showed a higher significant relative risk for thyroid nodules in the exposed subjects. CONCLUSION--The results suggest that occupational exposure to radiation may be a risk factor for thyroid nodules.     

Assessment of interstitial lung disease in systemic sclerosis using the quantitative CT algorithm CALIPER

Clinical Rheumatology - Interstitial lung disease (ILD) remains a major cause of morbidity and mortality in systemic sclerosis (SSc). Study aim is to characterize and quantify SSc-ILD by using...     

Acute renal failure and hypercalcemia as onset in splenic lymphoma

Hypercalcemia is a rare metabolic disorder in course of B cell lymphoma. The mechanism of hypercalcemia in patients with malignancy may include the increased extrarenal production of vitamin D from tumoral cells or neighboring macrophages, i-PTH or PTHrP from tumoral cells. In this case we reported a 34 years old caucasian woman with acute renal failure and hypercalcemia as onset of splenic lymphoma in absence of abnormal levels of serum vitamin D and PTHrP. Because of dramatic recovery of renal function and hypercalcemia after splenectomy, we can speculate that main mechanism of hypercalcemia is related to vitamin D production from neighboring lymphoma macrophages.     

Emerging oral drugs for relapsing-remitting multiple sclerosis

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), traditionally considered to be an autoimmune, demyelinating disease. The last two decades have witnessed the introduction of several therapies for MS. At present, there are five licensed first-line, disease-modifying drugs (DMDs) in MS and two second-line treatments. Nevertheless, in clinical practice DMDs or immunosuppressive treatments are frequently associated with suboptimal response in terms of efficacy and several side effects leading to poor patient adherence. AREAS COVERED: Since MS is a chronic disease, DMDs require long-term, regular injection or monthly parenteral infusions, which may be uncomfortable and inconvenient for the patient. Thus, there is an important need for new therapeutic strategies, especially those that may offer greater patient satisfaction in order to optimize therapeutic outcomes. Currently, five oral therapies are in Phase III development or have recently been approved for the treatment of relapsing-remitting MS: cladribine and fingolimod, the first approved in Russia and Australia, the latter is more widespread. Fumaric acid (BG-12), teriflunomide (A77126 or HMR1726) and laquinimod (ABR-215062) are in Phase III trials. Details of these five drugs will be covered in this review. EXPERT OPINION: Preliminary results indicate that oral medications are as effective as, or possibly more effective than, current injectable formulations. It is believable that improved outcomes will translate into higher real and perceived efficacy rates and contribute to improved adherence. The decision to switch established patients from injectable to oral medications will be made on balancing the efficacy and tolerability of the patient's existing therapy and their compliance history, even though safety is likely to become the most important factor in the future development of MS drugs.