Introduction
Synovitis, swelling, and joint degeneration are all caused by immune system mediators and antibodies, both innate and adaptive. Loss of tolerance to citrulline residues in self-proteins is caused by the interaction of genes and the environment. Arginine residues are converted to citrulline by peptidyl arginine deiminase following translation. The immune system targets patients who share epitopes, creating ACPAs (Volkov et al., 2020). There is evidence that inflammation and the formation of adhesion molecules in the synovium occur before the emergence of systemic autoantibodies in RA.
When leukocytes invade the synovium, a condition known as synovitis is induced. Synovial microvessels create adhesion molecules and chemokines, which cause leukocytes to move from distant sources into the synovium. As a result of synovial cell proliferation and reduced capillary flow, the interior of the inflamed synovium is hypoxic. Hypoxia enhances synovial angiogenesis, perhaps through an increase in VEGF synthesis. The development of rheumatoid arthritis (RA) is a complex process involving adaptive and innate immunological components. Cytokine and chemokine levels in the synovium significantly impact the dynamics of these interactions (Lin et al., 2020). Proliferating inflammatory cells populate the synovial membrane in RA and act synergistically to cause joint destruction.
As dendritic cells, critical antigen-presenting cells, are found near clusters of T cells in the synovium, RA’s adaptive immune response is likely involved. Dendritic cells deliver Antigens to T cells in the synovium, which is essential in T-cell activation. T-cell activation and downstream pathways are inhibited when CD80/86 is suppressed competitively. CD80/86 inhibition’s success in treating RA shows that T cells play a role in the disease’s development.
Th1, Th2, and Th17 subpopulations form when T cells get activated, each having distinct cytokine production profiles and responsibilities. The adaptive immune system also influences RA’s etiology. B cells can play a role in autoimmune disease in various ways. B-cell tolerance checkpoints can be defective, allowing autoreactive B cells to activate T cells as antigen-presenting cells. The cytokines they generate might be pro- or anti-inflammatory (Weyand & Goronzy, 2021). As a result, B cells are now capable of producing antibodies. RA can be brought on by anyone or a combination of these mechanisms. The synovial membrane is home to macrophages, mast cells, and natural killer cells, whereas the synovial fluid is home to neutrophils. Synovitis macrophages release proinflammatory cytokines, reactive oxygen intermediates, prostanoids, and matrix-degrading enzymes. Pathogen-inducing stimuli such as a pathogen elicit an inflammatory and immunological response from TLRs on macrophages and dendritic cells in the body.
Intracellular signaling networks are involved in the pathogenesis of RA. Antibodies and antigens generate inflammation by binding to receptors on target cells. Intracellular signaling events lead to the nucleus, where gene expression is altered, influencing cell function due to receptor interaction. Variations in the production and release of inflammatory mediators are commonly associated with immune cell gene expression variations. The original signal is amplified and modified when these mediators are released extracellularly. A healthy immune response necessitates intracellular signaling networks, which might be impaired in autoimmune illness. It is now being used in the treatment of RA, the first generation of small intracellular molecules. New therapy targets might be discovered by further investigation of these pathways.
Treatment
Medications
The symptoms and RA length will influence the drugs the doctor recommends.
- NSAIDs. Inflammation and discomfort can be reduced by using NSAIDs. Aspirin (Advil, Motrin IB) and naproxen sodium (Aleve) (Aleve). Over-the-counter NSAIDs lack the potency of prescription medications (Lin et al., 2020). In addition to stomach pain and palpitations, kidney impairment might result from using this medication.
- Steroids: Prednisone and other corticosteroids like Prednisone slow down the degradation of joints. Diabetes, obesity, and bone loss are all symptoms of osteoporosis. Corticosteroids are usually administered quickly to minimize adverse effects.
- DMARDs: These drugs can help rheumatoid arthritis patients prevent joint and tissue damage that cannot be reversed with conventional treatment. Sulfasalazine and methylchloroquine (Plaquenil) are examples of DMARDs (Azulfidine). Liver and lung infections are two possible side effects.
- Biology: It is worth noting that the most recent DMARDs on the market include the previously mentioned DMARDs abatacept (Orencia), etanercept (Orencio), infliximab (Rituximab), and rituximab (Orencio) (Actemra).
- Therapy: A physical or occupational therapist can teach joint flexibility exercises under the doctor’s direction. They may also suggest less taxing daily routines for one to follow. One can elevate objects with the forearms. Assistive gadgets can help alleviate pain in the joints.
Surgery
Surgery may be required if medication-induced joint damage occurs. In some cases, joint function can be restored following surgery (Bullock et al., 2018). In terms of pain and function, this vitamin can be beneficial.
Surgery for rheumatology includes:
- Synovectomy: To alleviate discomfort and improve range of motion, it is recommended that inflammatory synovium be removed (joint lining).
- A tendon injury: The strain on a tendon can be exacerbated by joint inflammation and damage. After surgery, one may be able to grow new tissue.
- Synthesis: Joint replacement may be avoided in favor of surgical fusion to provide stability, realignment, and pain relief.
- Joint replacement: If one of the joints is damaged, a metal and plastic replacement is implanted into the body.
Summary of the Interview
A common autoimmune illness, RA manifests itself in inflammation and swelling of the joint is synovium. If left untreated, it can result in the loss of the joint is bony and cartilaginous components, resulting in incapacity. There is a wide range of comorbidities associated with systemic inflammation, all of which have a part in the increased death rates reported in those who have RA. The pathophysiology of RA is still largely unknown, although antigen presentation, T-cell activation, and autoantibody production are all thought to play a part in the inflammatory process (Weyand, & Goronzy, 2021). The medical history of the patient, as well as the physical examination, are utilized to identify whether or not the patient has rheumatoid arthritis. To aid in developing therapeutic interventions, markers of disease activity have been developed.
References
Bullock, J., Rizvi, S. A., Saleh, A. M., Ahmed, S. S., Do, D. P., Ansari, R. A., & Ahmed, J. (2018). Rheumatoid Arthritis: A Brief Overview of the Treatment. Medical Principles and Practice, 27(6), 501-507.
Lin, Y. J., Anzaghe, M., & Schülke, S. (2020). Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis. Cells, 9(4), 880.
Volkov, M., van Schie, K. A., & van der Woude, D. (2020). Autoantibodies and B Cells: The ABC of Rheumatoid Arthritis Pathophysiology. Immunological Reviews, 294(1), 148-163.
Weyand, C. M., & Goronzy, J. J. (2021). The Immunology of Rheumatoid Arthritis.Nature Immunology, 22(1), 10-18.