1. RHEUMATOID ARTHRITIS MUHAMMAD ADEEL (BIOT 412) Human Diseases Presentation

2. Introduction In layman terms, Rheumatoid Arthritis can be described as a chronic multisystem disease that causes the inflammation of joints and its surrounding tissues as well. It is an auto immune disorder. In technical terms, lymphocytic infiltration of the synovium takes place.

3. Diagrammatic Representation

5. Cause & Mechanism The exact cause has not been identified as yet. Role of immune system has been well established in the spread of RA. HLA DR 4 is involved in the auto immune response. Release of cytokines causes inflammation. The autoantibody released in the process is known as the Rheumatoid Factor (RhF). These factors and an immunoglobulin (Ig G) form complexes that lead to the disease process.

6. Causes & Mechanism: 2 Macrophages release enzymes, which trigger response from neutrophils, leading to bone deformity. The disease affects in a symmetric manner. Which means that both joints would be equally affected. Pain can be felt even while resting.

7. Mechanism

8. Symptoms Fatigue Loss in Hunger Low Intensity Fever Pain in muscles and joints Stiffness Symmetric pain/Joints become swollen Burning in eyes Drying of mouth

9. Prevelance Worldwide, the annual incidence of rheumatoid arthritis is approximately 3 cases per 10,000 population, and the prevalence rate is approximately 1%, increasing with age and peaking at age 35-50 years. Age Group: 40’s onwards (Juvenile cases are rare) In Pakistan, 8% of the population above the age of 40 suffers. 3 times more in women than men. Disease progresses with age.

10. Genetic or Behavioral? Both! Genetic Quotient of the disease: Genetic Variance, Incomplete penetrance, HLA Genes Behavior Quotient of the disease: Smoking (affect proteins in the immune system which might lead to auto immune response)

11. Diagnostics 1. Blood Tests A) ESR B) C reactive Protein C) Color of Synovial Fluid 2. Imaging X Ray MRI Ultrasound Scans

12. Treatment Available on four levels A) Drugs (Analgesics/NSAID’s) B) Physical Therapy C) Surgery D) Biological Therapy (Most important)

13. What are disease modifying anti-rheumatic drugs ? The basic target of these drugs is not to lessen pain but to address the main disease. Examples would include gold injections and sulfasalazine among others. Some of them are immunosuppressant as well, and limit the RF production.

14. Principle of Biological Therapy Molecule would bind to factors of immune system involved in RA and inhibit their activity. Example: Adalimubab: Binds to TNF alpha and stops it from activating TNF receptors. Trivia: Adalimubab is the first monoclonal antibody drug approved by FDA and is marketed by the name of HUMIRA ( Human Monoclonal Antibody in Rheumatoid Arthritis).

15. Structure

16. Research Perspective 1. Better Diagnostic Test Anti MCV Antibody Test (MCV is protein belonging to citrullinated vimentin family). Specificity of the test: 99.7! Point of care type immunoassay.

17. Research Perspective 2. Permanent Cure: Possible?  Innovation in moleculesFusion Proteins  It is now known that by altering the sugar structure of the antibody, better molecules can be made. This has been implemented in the case of a molecule rituximab, which has been glycol-engineered for enhancing its activity

18. Thank you!