22 - Science of Rheumatoid Arthritis Flashcards

1
Q

name 4 changes to a joint which has been affected by RA?

A

inflamed synovium, inflamed tendon sheath, thinning of joint cartilage and erosion of bone

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2
Q

name 4 functions of the synovium?

A

maintenance of tissue surface, lubrication of cartilage, control synovial fluid volume, nutrition of chondrocytes

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3
Q

what 2 substances make up the synovial fluid?

A

hyaluronan, lubricin

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4
Q

define RA?

A

chronic symmetric polyarticular inflammatory joint disease

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5
Q

which joints are usually affected by RA?

A

small joints of the hands and feet

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6
Q

how is rheumatoid synovitis characterised? (3)

A

inflammatory cell infiltration, synoviocyte proliferation and neoangiogenesis

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7
Q

describe the synovial fluid during RA flare?

A

contains neutrophils

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8
Q

what does synovial pannus cause?

A

bone and cartilage destruction

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9
Q

name 2 antibodies commonly associated with seropositive RA?

A

rheumatoid factors and anti-citrullinated protein antibodies (ACPA)

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10
Q

name 1 way in which autoantibodies can contribute to inflammation in RA?

A

activation of complement

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11
Q

how is seropositive RA diagnosed?

A

anti-CCP assays - these recognise ACPAs

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12
Q

name 4 of the ACPAs which may be present in seropositive RA?

A

alpha-enolase, keratin, fibrinogen, collagen etc.

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13
Q

which autoantibodies are associated with seronegative RA?

A

NONE

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14
Q

is there a genetic link with RA?

A

Yes - esp twins

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15
Q

which locus is associated with a risk of developing RA?

A

HLA-DRB1 locus

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16
Q

how does this locus play a role in promoting autoimmunity in RA?

A

molecular mimicry - these alleles containing common amino acid motif in the HLA-DRB1 region

17
Q

effect of smoking on RA?

A

increases risk - as well as bronchial stress

18
Q

give an example of 2 infectious agents which may increase risk of RA?

A

EBV, E. coli

19
Q

what does repeated insults in genetically susceptible individuals lead to?

A

formation of immune complexes and rheumatoid factor - this altered citrullination of proteins results in ACPA response

20
Q

what is citrullination?

A

the conversion of arginine into citrulline

21
Q

what enzymes are involved in citrullination?

A

peptidylarginine deiminases (PADs)

22
Q

name 3 examples of coexisting conditions to RA?

A

vascular disease, fracture, metabolic syndrome

23
Q

name 4 types of cells which are involved in synovitis in RA?

A

CD4+ T cells, macrophages, B cells, mononuclear cells

24
Q

name 2 types of stromal cell cytokines which are abundant in RA synovium?

A

macrophage and fibroblast cytokines

25
Q

what is the role of IL-6?

A

mediate systemic effects

26
Q

what is the role of neoangiogenesis?

A

to provide nutrients to hyperplastic synovium

27
Q

how is bone destruction mediated in RA?

A

by osteoclasts that are activated by RANKL (produced in synovium) and fibroblast-like synoviocytes

28
Q

name 2 genes which are implicated in susceptibility to RA?

A

class II major histocompatibility complex genes and PTPN22

29
Q

when can increased serum levels of RFs and anti-CCP be seen?

A

years before onset of arthritis

30
Q

name 2 therapeutic target cytokines?

A

TNF-alpha and IL-6

31
Q

name 4 systemic effects secondary to uncontrolled inflammation due to RA?

A

vasculitis, nodules, scleritis, amyloidosis

32
Q

name 5 potential systemic complications of RA?

A

2y fibromyalgia, anaemia, osteoporosis, fibrosis, 2y Sjorgen’s syndrome