Question

1. Rheumatoid Arthritis (RA) is an inflammatory autoimmune disease. One targeted treatment is Tofacitinib. Tofacitinib blocks the production of JAKS, preferentially inhibiting JAK1 and JAK3. Tofacitinib can reduce the signs and symptoms of RA. JAK signaling affects many cells and pathways and the exact mechanism by which Tofacitinib is having an impact is unknown. Using what you know of inflammation and autoimmunity; how in general could blocking the production of JAKS decrease the inflammation driven symptoms of RA (note: this is not asking for a signaling pathway; ‘JAK signaling’ is descriptive enough; 5 marks)?

Answer 1

RHEUMATOID ARTHRITIS IS A AUTOIMMUNE DISEASE.

The joint inflammation of rheumatoid arthritis(AR) causes swelling, pain,stiffness and redness in the joints . The inflammation of RA disease can also occur in tissues around the joints such as tendons, ligament and muscles.

Autoimmunity is the system of immune response of an organisam against its own healthy cells and tissues. Any disease that result from such an aberrant immune response is termed an autoimmune disease. A chronic inflammatory disorders affecting many joints, including those in the hands and feet.In RA , the body's immune system attacks its own tissue,including joints. In severe cases it attacks internal organ.Rheumatoid arthritis and psoratic arthritis are common among the most common types of autoimmune arthritis.symptoms of autoimmune arthritis.

1. Fatigue 2. Fever 3. Joint pain 4. Stiffness 5. Swelling 6.weakness.

Proinflammatory cytokine activation ofjanus kinase/signal transducer and activators of transcription (JAK/STAT) signal transduction pathway a critical event in the pathogens and progression of RA. Under normal conditions JAK/STAT exemplified by the suppression of cytokine signaling and protein inhibitors of activated STAT . However in RA both of these regulators arw dysfunctional.Thus continues activation of JAK/STAT signaling in RA synovial joints results in the elevated level of matril metalloprotenase gene expression, increased frequency of apoptotic chondrocytes and most prominently apoptosis resistance in the inflammated synovial tissue.(JAKS function:Reference_www.ncbi.nlm.nib.gov).