23: The Science of Rheumatoid Arthritis

Question 1

the rheumatoid synovitis (pannus) is characterised by which processes?

Answer 1

• inflammatory cell infiltration
• fibroblast proliferation
• neoangiogenesis

Question 2

which auto-antibodies are commonly associated with RA?

Answer 2

• rheumatoid factor
• anti-citrullinated protein antibodies (ACPA)

Question 3

how do genes play a key role in susceptibility to RA and disease severity?

Answer 3

• association with HLA-DRB1 locus (HLA-DR4 serotype), strongest genetic link to RA.
• alleles containing a common amino acid motif (QKRAA - shared epitope) in the HLA-DRB1 region confer suceptibility.
• PTPN22 gene also implicated.

Question 4

which environmental factors can increase suceptibility to RA?

Answer 4

• smoking and bronchial stress (exposure to silica)
• infectious agents e.g. viruses (EBC, CMV), E.coli, mycoplasma, periodontal disease, microbiome (gut microbes)
• hormones

Question 5

repeated environmental insults in an indiviudal genetically susceptible to RA would lead to:

Answer 5

• formation of immune complexes and RF (high-affinity autoAb against the Fc portion of Ig)
• altered citrullination of proteins and breakdown of tolerance, with resulting ACPA response

Question 6

what is citrullination?

Answer 6

the conversion of the amino acid arginine in a protein into the amino acid cirtulline.

Question 7

which immune cells are present in the synovial fluid, especially during an RA flare?

Answer 7

neutrophils

Question 8

what enhances neoangiogenesis in the synovium?

Answer 8

hypoxic conditions and angiogenic factors such as IL-8 and VEGF

Question 9

bone destruction in RA is mediated by?

Answer 9

osteoclasts that are activated under the influence of RANKL produced by RA synovium.

Question 10

which cells cause cartilage destruction in RA?

Answer 10

• Synovial lining fibroblasts can attach to and invade cartilage in RA
• Several classes of proteases, including metalloproteinases and aggrecanases are produced by pathogenic synovial fibroblasts (as well as activated chondrocytes)

Question 11

list the key cytokines involved in chronic inflammatory arthritis

Answer 11

• TNF-alpha
• IL-1
• IL-6
• RANK-ligand (OPGL)
• IL-17

Question 12

name a b-cell inhibitor used to treat RA

Answer 12

rituximab

Question 13

name a t-cell inhibitor used to treat RA

Answer 13

abatacept