Genetic Predisposition: The most notable genetic association is with the HLA-DRB1 gene, specifically the shared epitope variant. People carrying this variant have a higher risk of developing RA.
Immune System Dysregulation: RA is an autoimmune disease, meaning the immune system mistakenly targets healthy tissues. Genetic factors influence immune responses, affecting the balance between pro-inflammatory and anti-inflammatory signals.
Cytokines and Signaling Pathways: Genes involved in cytokine production (e.g., TNF-alpha, IL-6) and signaling pathways (such as the NF-ÎșB pathway) impact RA development. Dysregulation of these genes contributes to chronic inflammation in the joints.
Epigenetic Modifications: Epigenetic changes (alterations in gene expression without altering the DNA sequence) can be influenced by genetic factors. These modifications affect immune responses and may contribute to RA susceptibility.
In summary, while environmental factors also play a role, genetic predisposition significantly influences the risk of developing rheumatoid arthritis. Early diagnosis and management are crucial for better outcomes. đđ
Pathogenesis
Ms. Jones presents with classic symptoms of rheumatoid arthritis (RA), an autoimmune disease causing chronic inflammation of the joints. In an autoimmune disease, the body's immune system mistakenly attacks healthy tissues. In RA, the immune system attacks the synovium, the lining of the joints, leading to inflammation, pain, and joint damage. Her morning stiffness, symmetrical joint pain, and positive serological tests (anti-CCP and RF) strongly suggest RA. X-rays, while not definitive for early RA, show mild joint space narrowing which can be a developing feature.