Rheumatoid arthritis (RA) is an autoimmune disorder that affects more than 1.5 million people in the United States (1). It was first thoroughly described in 1800 by Dr. Augustin Jacob Landré-Beauvais (2). Despite the fact that the causes of this disease are still not fully understood, it has been determined that RA is acquired due to a combination of environmental and genetic factors. Because RA most commonly affects the elderly, prolonged life expectancy across the population has had a striking impact on RA prevalence, or the number of people suffering from this condition.
A Worldwide Problem
RA is a peripheral polyarthritis that leads to the destruction of the joints through the erosion of cartilage and bone. Initially, RA results in inflammation of the joints and of the synovial membrane that covers them. The inflammation damages the cartilage and can gradually lead to the destruction of the joint. Some of the symptoms that follow inflammation of the synovial membrane include pain, fatigue, and fever.
Primarily, RA symmetrically affects the wrists and hands, but it may also damage other extremities or other parts of the body. Therefore, if left untreated, RA can affect mobility and other physical functions (3). Other organs such as the skin, lungs, heart, and kidneys are also frequently affected in different ways by RA. More severe potential consequences of RA are cardiovascular disease and cancer, and even though current treatments can improve quality of life for a vast number of patients, in some extreme cases rheumatoid arthritis can still cause death (1,3).
The Genetic Factor
The utilization of diverse protein analysis methods have proven that rheumatoid arthritis is frequently associated with HLA-DR4, the serotype that recognises the DRB1*04 gene products (4). The HLA system is partially responsible for the recognition of foreign molecules and the immune response. Certain alleles of HLA-DR4 appear in 60-70% of patients who have been diagnosed with RA (5). In most of these cases, patients present a more extent sequence of amino acids in the beta chain of the HLA-DR (5).
Polymorphisms of other genes have also been detected as contributors to increased risk for RA. One example is the protein tyrosine phosphatase non-receptor type 22 and its functional allele R620W, which regulates the activity of T lymphocytes (6). Polymorphisms of genes involved in the regulation of some cytokines, such as the tumor necrosis factor (TNF), have also been proven to increase the chances of developing RA (6).
Aside from genetics, the most relevant environmental factor associated with RA is smoking. Furthermore, women are up to three times more likely to develop RA than men (7).
Present and Future Treatments
The treatments that can be applied depend on the stage of the disease. The three phases of RA progression are (8):
The initiation phase, when the first signs of inflammation appear
The amplification phase, when the specific immune response is triggered
The chronic inflammatory phase, when the tissue injury due to the synthesis of interleukins and the activity of cytokines
The most commonly used medications are focused on reducing pain and inflammation. However, surgery is often recommended in cases of more severe RA (8).
Disease-modifying antirheumatic drugs (DMARDs) are administered to reduce the progression of the disease. They can be biological or synthetic, and they operate as inhibitors or antagonists of the TNF and many interleukins that are involved in the inflammatory response (9). Some of the most frequently used drugs are infliximab, golimumab, sulfasalazine, and adalimumab, among others. Steroids can also help to reduce symptoms and correct mobility. A good response to some of these treatments helps to improve quality of life for patients with RA (10).
There is enough evidence to support that future treatments will be mainly based on utilizing the already well studied DMARDs, which inhibit the activity of the TNF, in combination with drugs that block angiogenesis, or the formation of new blood vessels. As angiogenesis substantially contributes to the pathogeny of the disorder, even though further research needs to be done, this appears to be the most suitable mechanism for stopping the development of the RA (9).
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Spalinger M, et al. Protein Tyrosine Phosphatase Non-Receptor Type 22 Modulates NOD2-Induced Cytokine Release and Autophagy. PLoS One. 2013; 8(8): e72384. Published online 2013 Aug 26. doi: [10.1371/journal.pone.0072384].
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