The Science Of Rheumatoid Arthritis

Question 1

Functions of the synovium?

Answer 1

Maintenance of intact tissue surface,
Lubrication of cartilage,
Control of synovial fluid volume and composition (hyaluronan, lubricin),
Nutrition of chondrocytes within joints

Question 2

Pathology of RA?

Answer 2

Polyarticular inflammatory joint disease, there is rheumatoid synovitis (pannus), which is characterised by inflammmtory cell infiltration, synoviocyte proliferation and neoangiogenesis

Question 3

What does a synovial pannus cause?

Answer 3

Bone and cartilage destruction

Question 4

What autoantibodies are associated with RA?

Answer 4

RFs and anti-Citrullinated protein antibodies

Question 5

What gene is Rheumatoid Arthritis associated with?

Answer 5

HLA-DRB1,
PTPN22,
CTLA4,
C-REL

Question 6

What environmental factors have been associated with rheumatoid arthritis?

Answer 6

Smoking, 
Bronichial stress, 
Viruses (EBV, CMV), 
E.coli.,
Mycoplasma, 
Periodontal disease, 
Microbiome

Question 7

How do environmental factors link to rheumatoid arthritis?

Answer 7

Repeated insults lead to formation of immune complexes and rheumatoid factor and
Altered citrullination of proteins and breakdown of tolerance, which result in ACPA response

Question 8

Pathology of synovitis in RA?

Answer 8

There is villous hyperplasia,
Infiltration of T cells, B cells, macrophages and plasma cells,
Initial cell proliferation (fibroblasts),
Production of cytokines and proteases,
Increased vascularity,
Self-amplifying process

Question 9

What is synovitis?

Answer 9

Inflammation of the synovium

Question 10

How does Abatacept work in RA?

Answer 10

Is a fusion protein CTLA4-IgG1 that blocks T cell costimulation

Question 11

What is the role of inflammatory cytokines?

Answer 11

They induce the expression of endothelial-cell adhesion molecules,
Activate synovial fibroblast, chondrocytes, osteoclasts,
Promote angiogenesis,
Suppress T-regs,
Activate leukocytes,
Promote autoAb production

Question 12

What systemic effects does IL-6 mediate?

Answer 12

Acute-phase response,
Anaemia,
Cognitive dysfunction,
Lipid metabolism dysregulation

Question 13

In RA what is bone destruction by osteoclasts activated by?

Answer 13

RANKL produced by RA synovium

Question 14

Systemic complictions of RA?

Answer 14

Vasculitis, 
Nodules, 
Scleritis, 
Amyloidosis,
Cardio disease,
Fatigue, 
Reduced cognitive function, 
Liver disease, 
Lungs (interstitial lung disease, fibrosis),
Muscles (sarcopoenia),
Bone (osteoporosis),
Secondary sjorgen’s syndrome