Oxidative Stress in Autoimmune Rheumatic Diseases

Ankylosing Spondylitis (AS), Inflammatory Joint Diseases, Psoriatic Arthritis (PsA), Rheumatoid Arthritis (RA)

Rheumatoid arthritis, Psoriatic arthritis, Ankylosing spondylitis, Oxidative stress, Antioxidants

Rheumatic diseases constitute a group of non-communicable diseases characterized by chronic inflammation. The most common autoimmune rheumatic diseases (ARDs) are rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, myositis, Sjogren's syndrome and systemic scleroderma. These autoimmune disorders lead to joint destruction and adversely influence the human body systemically. One of their characteristics is comorbidity, since patients usually suffer also from other pathologies such as cardiovascular diseases and obesity. In addition, their treatment requires a combination of both biological and conventional pharmaceutical interventions as well as other parameters such as physical activity programs, nutrition, and the use of smart electronic devices. Therefore, the ARDs burden health systems worldwide. Apart from the physiological manifestations of ARDs, specific changes are observed at the cellular and molecular level. A common biochemical/molecular symptom of these diseases is oxidative stress. This condition leads to the disturbance of blood and tissue redox status due to the excessive production of free radicals. Given that free radicals are highly reactive moieties with strong oxidative capacity against biomolecules (i.e., proteins, lipids, DNA), they compromise the efficacy of the intrinsic antioxidant mechanisms and, finally, induce the disruption of redox homeostasis. However, there is no sufficient data linking the levels of redox status of patients with the progression of ARDs over time. Indeed, the onset and symptoms of ARDs are intertwined with the disruption of the patient redox homeostasis and the induction of oxidative stress. Concurrently, the absence of a completely effective pharmaceutical treatment emerges the need for the adoption of novel biomarkers for monitoring the severity of the symptoms and the evolution of ARDs in general. To that end, this study aims at first to investigate the blood redox status of patients with ARDs. Thus, specific redox biomarkers will be evaluated in the blood of patients in three time points (i.e., at Days 1, 180 and 360), and they will be associated with the clinical manifestations of their diseases. The ultimate goal is to clarify whether these biomarkers could putatively exert clinical significance, namely whether they could constitute an additional tool for the monitoring of the progression of these diseases in clinical practice.

Background: In recent years, there has been a significant increase in the incidence of chronic inflammatory non-communicable diseases worldwide, which are responsible for 71% of deaths annually. The prevention of these diseases has been associated with dietary habits and physical activity, while their auxiliary use along with the appropriate pharmaceutical interventions can also contribute to the reduction of their severity. Autoimmune rheumatic diseases (ARDs) are a group of non-communicable diseases characterized by chronic inflammation, that lead to joint destruction, and adversely affect human body. The most common ARDs are rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, myositis, Sjogren's syndrome and systemic scleroderma. The etiology of ARDs is rather complex. It is noteworthy that significant side effects are observed in patients receiving specific drug therapy, while some of them are resistant to existing drugs. According to available data, the incidence of rheumatic diseases is estimated at 0.5-1%. However, these diseases particularly burden health systems on a global scale. This is the case not only because one of their characteristics is comorbidity, since patients usually suffer from other diseases such as cardiovascular diseases and obesity, but also because of the use of biological medicines. On this basis, their management requires a combination of biological and conventional pharmaceutical interventions, as well as other parameters such as physical activity programs, nutrition and the use of smart electronic devices. Along with the physiological manifestations of ARDs, they share a biochemical/molecular symptom, namely oxidative stress. Oxidative stress is a condition that consists of the disturbance of redox state of blood and tissues due to the excessive production of free radicals. The latter are highly reactive molecules or atoms able to oxidize biomolecules (i.e., proteins, lipids, DNA). Specifically, in oxidative stress context, the concentration of blood antioxidant molecules is reduced, making biomolecules susceptible to potential oxidation and, therefore, to damage of their normal function. Oxidative stress is associated to inflammation and, therefore, is observed in ARDs by affecting normal cell signaling and disrupting redox homeostasis. Nevertheless, to our knowledge, there is no available data linking the levels of blood redox status of patients with the progression of ARDs over time. Methods: The levels of specific and widely established redox biomarkers will be evaluated in blood samples of the volunteering patients in three time points (i.e., Days 1, 180 and 360) to assess their blood redox status. The battery of the redox biomarkers that will be measured is as follows: The concentration of reduced form of glutathione (GSH) which is a crucial antioxidant metabolite, the activity of catalase, a potent antioxidant enzyme, total antioxidant capacity (TAC) as a crude indicator of blood antioxidant potential and concentration of protein carbonyls as a biomarker of protein oxidation. Moreover, C-reactive protein and erythrocyte sedimentation rate as indices of inflammation of the volunteers, as well as the severity of the ARDs through DAS28, PASI and SLEDAI tools will also be estimated. Finally, data regarding the following parameters will be collected: i) physical activity through the international physical activity questionnaire, ii) health status through the health assessment questionnaire, iii) quality of life through the Nottingham health profile questionnaire, iv) fatigue through the fatigue severity scale instrument and by using a visual analogue scale, v) sleep quality through the Pittsburgh sleep quality index and vi) nutritional habits through an one-day recall diary. Finally, the medication history of every patient as well as possible changes in medication will also be recorded. Anticipated outcomes: The levels of redox biomarkers will, at first, give insight about the baseline (i.e., at Day 1) oxidant/antioxidant state in the blood of the patients. In addition, blood redox biomarkers will be correlated to all measured parameters and their potential to diagnose/project the progression of ARDs will be examined. It is expected that blood redox biomarkers could serve as putative diagnostic tools regarding the progression of ARDs and the change in medication.

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