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Journal of Orthopedics and Physiotherapy

Volume : 1 Issue : 1

Emerging Discoveries in Rheumatoid Arthritis Research: Current Updates and Future Prospects

Ahed J Alkhatib1,2,3

1Department of Legal Medicine, Toxicology and Forensic Medicine, Jordan University of Science & Technology, Jordan 
2International Mariinskaya Academy, department of medicine and critical care, department of philosophy, Academician secretary of department of Sociology 
3Cypress International Institute University, Texas, USA

Corresponding author
Ahed J Alkhatib, Department of Legal Medicine, Toxicology and Forensic Medicine, Jordan University of Science & Technology, Jordan.

Rheumatoid arthritis, also known simply as RA, is a persistent inflammatory disease that mostly impacts the joints and is characterized by inflammation, pain, and swelling in those joints. The main objective of the present study was to conduct a review study regarding RA. It is a degenerative condition that, over time, can cause abnormalities in the joints and a loss of function in those joints. Although the precise reason for the development of RA is unknown, it is believed that both hereditary and environmental factors have a part in the condition. Medication, physical therapy, and behavioral adjustments are the three main components of a standard treatment plan for rheumatoid arthritis (RA). Even while there is no known treatment that will reverse the effects of RA, early diagnosis and intensive treatment can help patients manage their symptoms and delay the disease’s progression. Current research is aimed at creating novel medicines for rheumatoid arthritis (RA) that are more successful. The ultimate goal of this study is to improve the quality of life for those who are coping with this hard condition.

Keywords: Autoimmune Disease, Inflammation, Joint Pain, Joint Stiffness, Joint Swelling, Rheumatoid Factor

Rheumatoid Arthritis (RA): An Overview
Rheumatoid arthritis (RA) is a chronic inflammatory illness that causes joint swelling, pain, and synovial joint degeneration, resulting in severe disability. RA is classified as an autoimmune disorder [1]. According to a study conducted in the United Kingdom, the prevalence of RA in the general population is 1.16 percent in women and 0.44 percent in males [2].

Rheumatoid arthritis (RA) is a systemic autoimmune disorder that predominantly affects the joints. RA is characterized by synovial inflammation, joint pain, swelling, and destruction of cartilage and bone. The prevalence of RA varies globally, and it is estimated to affect around 1% of the world’s population [3].

RA is more common in women than in men, with a female-to-male ratio of approximately 3:1 [4]. The incidence and prevalence of RA increase with age, with the highest rates occurring in those over the age of 65 [5].

The diagnosis of RA is based on clinical examination, laboratory tests, and imaging studies. The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have established criteria for the diagnosis of RA, which include the presence of joint symptoms, laboratory abnormalities, and imaging findings [1].

A combination of pharmacologic and non pharmacologic treatments, such as disease-modifying antirheumatic medications (DMARDs), nonsteroidal anti-inflammatory medicines (NSAIDs), corticosteroids, and physical therapy, is used to treat rheumatoid arthritis (RA). Diagnosis and treatment of RA at an early stage are both essential for reducing the risk of joint damage and disability [3].

In conclusion, rheumatoid arthritis (RA) is a prevalent autoimmune condition that mostly impacts women and whose prevalence rises with increasing age. Early diagnosis and treatment are critical in preventing joint injury and disability.

Rheumatoid arthritis (RA) is an inflammatory illness that causes inflammation in the joints. The presence of autoantibodies in RA patients’ serum has revealed a lot about the disease’s biology. RA can be separated into seropositive and seronegative illness based on the presence of autoantibodies such as rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP), and more recently anti-acetylated protein antibodies. Specific human leukocyte antigen (HLA) alleles and smoking are linked to the development of these autoantibodies, which are linked to both genetic and environmental risk factors for RA. In a subset of individuals, autoantibodies can be found many years before disease manifestation, implying a series of events in which the initial autoantibodies develop in susceptible hosts, followed by an inflammatory response and clinically evident arthritis. The features and effector roles of these autoantibodies are being studied in order to gain a better understanding of the pathophysiological processes that underpin arthritis in RA. Recent research reveals that ACPA may play a role in the persistence of inflammation once it has begun. Furthermore, pathophysiological mechanisms establishing a direct relationship between the presence of ACPA and both bone erosions and pain in RA patients have been established. Finally, examining autoantibodies’ potential harmful potential could lead to a better understanding of the underlying pathophysiological mechanisms in rheumatoid arthritis [6].

Rheumatoid arthritis, also known simply as RA, is a persistent autoimmune condition that mostly impacts the joints. Rheumatoid arthritis (RA) is a heterogeneous disease characterized by the presence of several disease subtypes, each of which is most likely caused by a distinct underlying cause. These diverse pathophysiological pathways may, through a final common inflammatory pathway, result in a clinical presentation of arthritis that is comparable to that of the disease. The two most common forms of RA, known as ACPA-positive and ACPA-negative disease, are distinguished from one another by the risk factors and clinical outcomes they present [5]. Patients with rheumatoid arthritis have been shown to have elevated levels of many autoantibodies in their serum, the most notable of which are rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Antibodies against additional posttranslationally changed proteins have recently been discovered. Examples of these antibodies include anti-carbamylated protein antibodies (anti-CarP) and anti-acetylated protein antibodies (anti-ACP) [7,8]. Both of these studies were conducted by Shi et al. and Juarez et al., respectively. The majority of contemporary study on autoantibodies and their function in the pathophysiology of disease has been on ACPA, which are anti-citrullinated protein antibodies. Citrullination is a chemical reaction that is catalyzed by peptidyl-arginine deiminase (PAD) enzymes. This reaction changes the DNA-encoded amino acid arginine into citrulline. A posttranslational change can occur as a consequence of both healthy and pathogenic situations. It is believed that the development of an immune response to citrullinated proteins, and consequently the generation of ACPA, is linked to several of the established risk factors for rheumatoid arthritis (RA) [9].  

Autoantibodies in RA
It is believed that between 50 and 80 percent of patients diagnosed with RA have autoantibodies [5]. As was said earlier, the discovery of autoantibodies made it possible to classify rheumatoid arthritis patients into subgroups that are more similar to one another in terms of the risk factors involved and the clinical course of the disease. An autoantibody called RF, which is directed against the Fc component of human IgG, was the first autoantibody system to be characterized in RA. The presence of RF was considered sufficiently characteristic of RA in 1987 that it was included in the criteria for RA categorization by the ACR, despite the fact that its specificity was low. A number of decades later, the RA-specific ACPA was discovered [6]. The ACR-EULAR 2010 categorization criteria for RA incorporates both RF and ACPA within its evaluation process. Recently, antibodies that target other posttranslationally altered proteins, like carbamylated and acetylated proteins, have been found [7,8]. Seropositive rheumatoid arthritis has been associated to a quicker radiographic development and joint destruction whereas seronegative rheumatoid arthritis patients present with more inflammatory markers [10,11]. In addition, the presence of many autoantibodies may be just as important as the presence of a single autoantibody when it comes to classifying the various phenotypes of RA patients. This is because the presence of a single autoantibody is not enough to determine a patient’s phenotype [6]. Autoantibodies not only provide information on the course of the disease, but they also offer insight into the pathogenesis of RA. Research into the numerous autoantibodies and the qualities that they possess has led to a greater understanding of the underlying pathophysiological mechanisms that are at play in rheumatoid arthritis [6].

Anti-Citrullinated Protein Antibodies
As was mentioned before, the production of citrullinated peptides takes place as a result of a posttranslational modification that is mediated by PAD enzymes. Antibodies against citrullinated peptides of various isotypes, such as IgG, IgA, and IgM, have been found in patients with rheumatoid arthritis (RA) [12]. The existence of ACPA IgA lends credence to the theory that ACPA is associated with either smoking or microbiome dysbiosis. This is due to the fact that IgA is associated with a mucosal origin of the immune response. Citrullinated proteins can be found in the synovial fluid of RA joints that are inflammatory, which suggests that ACPA could potentially bind to these antigens in the joint and exacerbate the local inflammation [13]. Vimentin has been suggested as a possible target protein for ACPA. In mouse models of collagen-induced arthritis (CIA), passive transfer of ACPA does not cause synovitis to develop from scratch, but it does have the potential to exacerbate pre-existing synovitis [14]. As a consequence of this, many “hits,” or exposures, are assumed to be necessary before the development of RA. Autoantibodies, according to one view, may be the cause of the non-resolution and chronicity of a generally brief immune response, such as following trauma or infection. This theory is based on the idea that autoantibodies may be produced by the body.

Anti-Acetylated Protein Antibodies
The most recent addition to AMPAs in RA patients is anti-acetylated protein antibodies, which have been found in approximately forty percent of people who have RA, especially in the group of people who have ACPAs that are positive. Due to the fact that the detection rates in seronegative RA patients were comparable to those in individuals with arthritis that was improving, it seems doubtful that these antibodies will become a novel biomarker for diagnosing RA [8]. Anti-acetylated protein antibodies, on the other hand, have the potential to reveal major new insights into pathophysiology, which is especially important in this day and age, when the microbiome seems to be assuming an increasingly important role. The acetylation process is an enzyme process, and microorganisms have the ability to alter it. The fundamental mechanism for this process is not known. Anti-acetylated antibodies could therefore reveal a novel relationship between the dysbiosis of the microbiome and the beginning of autoimmunity in RA [15].

Pathogenic Potential of Autoantibodies
The expansion of the ACPA repertoire prior to the onset of sickness and the correlation between the presence of autoantibodies and radiographic progression are both strong indicators that the anti-citrulline immune response may be involved in the pathophysiology of the disease. In addition to this, rituximab-mediated B cell reduction is effective in RA patients, with higher efficacy in ACPA- and RF-positive cases. This suggests that B cells (and maybe the autoantibodies they make) have a role in the pathogenesis of the disease [16]. According to numerous pieces of evidence, autoantibodies appear to play a pathogenic role in rheumatoid arthritis (RA). Figure 1 is a depiction of the model that discusses the likely function that autoantibodies play in the disease pathophysiology of RA. This model was explored in this review.

Binding to FC Receptors
In general, antibodies have the ability to exert an influence on other cells through the binding of Fc receptors. Immune complexes that contain ACPA and citrullinated fibrinogen, such as recall antigen immune complexes (ICs), have the ability to stimulate Fc receptors on macrophages, which in turn can lead to the generation of TNF [19]. The presence of RF-IgM or RF-IgA, which promotes complement activation and amplifies the immunological response mediated by Fc receptors, can change the effector activities of ACPA ICs [20]. This demonstrates that ACPA and RF may play a synergistic role in the pathogenesis of RA, which is confirmed by epidemiological studies which show that combining ACPA and RF is linked to increased disease activity. This suggests that combining ACPA and RF may be associated with a greater risk of developing RA [21].
Complement Activation.

Activation of complement is yet another significant effector activity that antibodies can have. There are three different ways that the complement system can be activated: the classical pathway, which is begun by C1q; the alternative pathway, which is started by C3; and the lectin pathway, which is started by mannose-binding lectin (MBL). Chemotaxis, membrane attack complex formation, and optonization are all processes that bacteria engage in. The levels of complement in the synovial fluid of RA patients are lower, but the levels of complement cleavage products are higher, which indicates that complement activation occurs more quickly. It has been shown that ACPA is capable of recruiting complement through both the classical and alternative pathways, but not through the lectin pathway [22]. When all of the information is considered together, it suggests that ACPA may improve immune response in RA by binding to Fc receptors and activating complement. This may be accomplished [23-28].

Rheumatoid arthritis, also known simply as RA, is a debilitating autoimmune condition that affects the body’s joints in addition to other organs. Inflammation, discomfort, stiffness, and swelling in the joints are all symptoms of this condition, which, if left untreated, can eventually result in deformities and a loss of function. RA is a degenerative disease that can strike anyone of any age, while it strikes women and adults over the age of 60 at a higher rate than younger people.

It is not known for certain what causes RA, but researchers believe it may be due to a confluence of hereditary and environmental risk factors that drive the immune system to launch an assault on healthy tissues throughout the body, including the joints. However, there are a number of medications that can help manage the symptoms of RA and reduce the advancement of the condition. Although there is no cure for RA, there are treatments available.

Nonsteroidal anti-inflammatory drugs, also known as NSAIDs, disease-modifying antirheumatic drugs, often known as DMARDs, and biologic treatments are typically used in conjunction with one another in the treatment of rheumatoid arthritis (RA). Along with helping to enhance joint mobility, physical therapy and exercise can also help alleviate joint pain and stiffness.

It can be difficult to live with RA, but many people who have the condition are able to lead full and active lives with the help of the appropriate treatment and adjustments to their lifestyle. It is essential to maintain open communication with a healthcare professional in order to formulate a treatment strategy that is adapted to your specific requirements and to remain current on the most recent findings in RA research and treatment options.


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