RHEUMATOID ARTHRITIS | PATHOGENESIS

Summary

In this tutorial, the speaker explains the etiopathogenesis of rheumatoid arthritis (RA), an autoimmune disease that primarily affects joints. RA leads to joint inflammation, cartilage destruction, and bone resorption, often causing ankylosis if not treated early. The video delves into the genetic factors (HLA gene loci) and environmental triggers (like smoking and infections) that contribute to RA. The immune response, involving both T and B cells, results in the production of autoantibodies, such as rheumatoid factor and anti-citrullinated peptide antibodies, which play a key role in diagnosing the disease. The session also introduces the AI-based study tool, Wisdia, for practice.

Takeaways

• 😀 Rheumatoid arthritis (RA) is an autoimmune disease that primarily affects joints, causing inflammation and potential joint damage.
• 😀 RA involves a failure of the immune system to recognize its own body tissues, leading to joint destruction and ankylosis (fusion of joints).
• 😀 The term 'rheumatoid arthritis' was coined by Sir Alfred Baring Garrod in 1859, derived from Greek words meaning joint inflammation.
• 😀 RA affects mainly diarthrodial joints, with symmetrical and bilateral involvement, particularly in the hands, feet, knees, elbows, and spine.
• 😀 Extra-articular manifestations of RA can involve organs such as the skin, heart, blood vessels, and lungs, leading to a broader disease impact.
• 😀 The prevalence of RA is around 1% in the USA, with peak incidence in individuals aged 30-50 years, and women are more commonly affected (3:1 ratio).
• 😀 The pathogenesis of RA involves genetic factors (e.g., HLA-DR genes) and environmental triggers like infections and smoking.
• 😀 Smoking and infections promote citrullination of joint proteins, leading to the production of anti-citrullinated peptide antibodies (ACPAs), a hallmark of RA.
• 😀 Key immune responses in RA involve T-helper 17 and T-helper 1 cells, which activate inflammatory pathways leading to joint damage through protease release.
• 😀 Autoantibodies like rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPAs) are key markers for RA, with ACPAs being highly specific for diagnosis.
• 😀 The formation of pannus (abnormal tissue growth in the joint space) contributes to joint destruction, chronic inflammation, and bone resorption in RA.

Q & A

What is rheumatoid arthritis (RA)?

Rheumatoid arthritis is an autoimmune disease that primarily affects the joints, leading to inflammation, destruction of joint cartilage, and eventual joint fusion, known as ankylosis, if not managed early.

Who coined the term 'rheumatoid arthritis' and what is its meaning?

The term 'rheumatoid arthritis' was coined by Sir Alfred Baring Garrod in 1859. The name is derived from Greek, where 'rheuma' means 'flowing' and 'arthron' means 'joint', indicating joint inflammation.

What are the primary joints affected by rheumatoid arthritis?

Rheumatoid arthritis primarily affects diarthrodial joints, such as the proximal interphalangeal joints, metacarpophalangeal joints, elbows, knees, ankles, and spine.

What is the prevalence of rheumatoid arthritis in the U.S.?

Rheumatoid arthritis affects approximately 1% of the population in the U.S. with the peak incidence occurring between the third and fifth decades of life.

What is the gender ratio in rheumatoid arthritis cases?

Rheumatoid arthritis is more common in females, with a gender ratio of 3:1 (females to males).

What are the two main factors involved in the pathogenesis of rheumatoid arthritis?

The two main factors involved in the pathogenesis of rheumatoid arthritis are genetic predisposition and environmental triggers, such as infections and smoking.

What role do environmental triggers play in the development of rheumatoid arthritis?

Environmental triggers, such as infections (e.g., periodontal disease) and smoking, promote the citrullination of self-proteins, which leads to the generation of new epitopes that trigger an autoimmune response.

What is citrullination and how does it relate to rheumatoid arthritis?

Citrullination is a post-translational modification where arginine residues in proteins are converted to citrulline. This process creates new epitopes that are recognized as foreign by the immune system, triggering the production of anti-citrullinated protein antibodies (ACPA), a hallmark of rheumatoid arthritis.

What are the two main T-cell responses involved in rheumatoid arthritis?

The two main T-cell responses in rheumatoid arthritis are the activation of **Th17** cells, which secrete interleukin-17 to recruit neutrophils and monocytes, and **Th1** cells, which secrete interferon-gamma to activate macrophages and promote inflammation.

What is pannus and how does it contribute to joint damage in rheumatoid arthritis?

Pannus is a proliferated tissue in the joint space that contains synovial hyperplasia and inflammatory cells. It contributes to joint damage by secreting proteases that destroy joint cartilage and by stimulating osteoclast activity, leading to bone resorption.

What are the three key autoantibodies associated with rheumatoid arthritis?

The three key autoantibodies in rheumatoid arthritis are: 1) **Rheumatoid factor (RF)**, which targets the Fc portion of IgG; 2) **Anti-citrullinated protein antibodies (ACPA)**, which target citrullinated proteins; and 3) **Anti-carbamylated protein antibodies**, which target carbamylated proteins.

How specific is anti-citrullinated protein antibody (ACPA) for diagnosing rheumatoid arthritis?

ACPA is highly specific for rheumatoid arthritis. Its presence is a strong indicator for the disease, as it targets citrullinated proteins found in the joints, and is found in 60-70% of RA patients.

What is the significance of the autoimmune mechanisms in rheumatoid arthritis?

The autoimmune mechanisms in rheumatoid arthritis lead to chronic inflammation, joint damage, and the formation of pannus. T-cell and B-cell responses, along with the production of autoantibodies, play a central role in sustaining the disease and contributing to joint destruction.