Ongoing Studies

Effect of Combined Low-Dose Radon- and Hyperthermia Treatment of Patients with Ankylosing Spondylitis on Serum Levels of TGF-β1, TNF-α, IL-6, OPG, RANKL and the OPG/RANKL-Ratio

Abstract

Ankylosing spondylitis (AS) is a rheumatic disease mainly characterized by inflammatory tissue destruction in axial joints and bilateral sacroiliitis. The chronic inflammatory processes may cause enhanced bone resorption, due to dysbalance of the biologic activity of the osteoclast – osteoblast system which frequently results in systemic osteoporosis, a typical extra-articular symptom severely affecting almost 50% of AS patients. Among several factors, Receptor Activator of Nuclear Factor kB ligand (RANKL) and its functional antagonist Osteoprotegerin (OPG) have been shown to be essential in the regulation of osteoclast biology. The ratio of RANKL and OPG, an important marker to assess the  status of systemic bone metabolism, has been shown to be dysregulated in AS patients. Combined low-dose radon- and hyperthermia therapy (LDRnHT) causes intermediate or long term pain reduction in patients with AS, which has been previously shown to correlate with elevated levels of the cytokine transforming growth factor-β1 (TGF-β1). Given the ability of TGF-β1 to ameliorate inflammation and to influence the OPG/RANK/RANKL system, we are currently investigating the effect of LDRnHT on serum levels of TGF-β1, OPG, RANKL as well as on other factors involved in chronic inflammatory disorders, like tumor necrosis factor (TNF)-α, Interleukin (IL)-6, IL-17 and PGE2 in the peripheral blood of AS-patients.

Effect of Combined Low-Dose Radon- and Hyperthermia Treatment of Patients with Ankylosing Spondylitis on Serum Titers of Antibodys directed against Cyclic Citrullinated Proteins

Abstract

Autoimmunity – the key feature of rheumatoid disorders including AS - manifests itself via production of antibodies against `self` antigens. Among several environmental and genetic factors that seem to predispose for rheumatoid arthritis (RA), formation of neo-antigens via altered post-translational modifications is believed to be strongly associated with the onset of autoimmunity and, subsequently, the pathogenesis of rheumatoid disorders. In fact, genetic  polymorphisms of  peptidyl-arginine-deiminase type IV (PAD IV), the enzyme that mediates citrullination of proteins, has been associated with the susceptibility to RA. Antibodies against cyclic citrullinated proteins (anti-CCP) target multiple citrullinated proteins and are highly specific for RA. Thus, anti-CCPs have become a useful diagnostic marker and a predictive tool for the progression of RA. Combined low-dose radon/hyperthermia therapy (LDRnHT) has been reported to improve mobility and reduce pain in patients with AS. As the mechanisms of action are still elusive, we are currently investigating the effect of LDRnHT on the level of circulating anti-CCPs in the peripheral blood of AS patients.