RA

Question 1

Rheumatoid Arthritis

Answer 1

-involve lots of cell types, macro,T/B, fibroblasts, chondrocytes, neutrophil, mast cell, dendritic cell

Question 2

Genes involved in RA?

Answer 2

Class II major histocompatibility complex genes - especially 5AA region HLA-DR4

PTPN22/PADI4
peptidylarginine deiminases

Question 3

Evidence of autoimmunity in RA?

Answer 3

-high serum autoantibodies - rheumatoid factors
and anticitullinated protein antibodies
-adaptive & innate immune response in synovium

Question 4

For RA, what factors are targeted by drugs?

Answer 4

-TNF, IL-6,

Question 5

For RA, what mediates bone and cartilage destruction?

Answer 5

• osteoclasts

- fibroblast-like synoviocytes

Question 6

Clinical Features of RA?

Answer 6

-insidious onset over weeks to months
Joint involvement: intermittent at onset, not migratory, develops into a persistent polyarthritis
-morning stiffness (>30min)
-swelling, warmth, erythema
-synovial fluid analysis (exudate yellow, increased white blood cells, decreased viscosity)

Question 7

Extraarticular features of RA?

Answer 7

Systemic: fatigue, anorexia, weight loss, weakness, aching/stiffness, low fever
prodrome: worse with increased activity
SKIN: rhematoid nodules (30%)
vasculitis-inflammation of blood vessels
-“palpable purpura”, ulceration
EYE: keratoconjuctivitis sicca “dry eyes”
Xerostoma “dry mouth”
Episcleritis & Scleritis - erosion of sclera
CARDIORESPIRATORY
NEUROLOGICAL

Question 8

Pathophysiologic mechanisms in RA?

Answer 8

• chronic inflammatory disease affecting primarily the synovium
• viruses, retroviruses, bacteria, mycoplasm are associated - single “pathogen” not likely
• stress though specialized receptors that recognize common molecules produced by pathogen in genetically susceptible person might contribute to breakdown of tolerance and sub. autoimmunity

Question 9

Anticitrullinated antibodies associated with what features in RA?

Answer 9

• these abs attack vimentin, fibrinogen, enolase, autoantigens
• T-cells get activate and then go and attack it
• more of these in smokers
• anti-CCP, more specific marker of RA than RF
• more aggressive, more bone/cartilage distraction, accelerated atherosclerosis

activate complement, IgE can sensitize basophils and mast cells leading to degranulation

Question 10

What do RA autoantibodies recognize?

Answer 10

joint antigens like type II collagen
systemic antigens like glucose phosphate isomerase
“synovial inflammation”

Question 11

Synovium in RA

Answer 11

• intimal lining hyperplasia and sublining infiltration with mononuclear cells (CD4, macro, B)
• intimal lining FLS display aggressive features
• macro: highly activated, produce cytokines
• lymph: infiltrate sublining/form aggregates w/germinal center
• sublining CD4 mainly display memory cell phenotype
• Dendritic: present antigens to T cells in synovial germinal centers
• Synovial B/plasma: antigen-driven mutation/ab+
• Mast cell: small molecule medi. of inflammation
• Neutro: rarely present in RA synovium, lots in synovial effusions