22 - Science of Rheumatoid Arthritis Flashcards
name 4 changes to a joint which has been affected by RA?
inflamed synovium, inflamed tendon sheath, thinning of joint cartilage and erosion of bone
name 4 functions of the synovium?
maintenance of tissue surface, lubrication of cartilage, control synovial fluid volume, nutrition of chondrocytes
what 2 substances make up the synovial fluid?
hyaluronan, lubricin
define RA?
chronic symmetric polyarticular inflammatory joint disease
which joints are usually affected by RA?
small joints of the hands and feet
how is rheumatoid synovitis characterised? (3)
inflammatory cell infiltration, synoviocyte proliferation and neoangiogenesis
describe the synovial fluid during RA flare?
contains neutrophils
what does synovial pannus cause?
bone and cartilage destruction
name 2 antibodies commonly associated with seropositive RA?
rheumatoid factors and anti-citrullinated protein antibodies (ACPA)
name 1 way in which autoantibodies can contribute to inflammation in RA?
activation of complement
how is seropositive RA diagnosed?
anti-CCP assays - these recognise ACPAs
name 4 of the ACPAs which may be present in seropositive RA?
alpha-enolase, keratin, fibrinogen, collagen etc.
which autoantibodies are associated with seronegative RA?
NONE
is there a genetic link with RA?
Yes - esp twins
which locus is associated with a risk of developing RA?
HLA-DRB1 locus
how does this locus play a role in promoting autoimmunity in RA?
molecular mimicry - these alleles containing common amino acid motif in the HLA-DRB1 region
effect of smoking on RA?
increases risk - as well as bronchial stress
give an example of 2 infectious agents which may increase risk of RA?
EBV, E. coli
what does repeated insults in genetically susceptible individuals lead to?
formation of immune complexes and rheumatoid factor - this altered citrullination of proteins results in ACPA response
what is citrullination?
the conversion of arginine into citrulline
what enzymes are involved in citrullination?
peptidylarginine deiminases (PADs)
name 3 examples of coexisting conditions to RA?
vascular disease, fracture, metabolic syndrome
name 4 types of cells which are involved in synovitis in RA?
CD4+ T cells, macrophages, B cells, mononuclear cells
name 2 types of stromal cell cytokines which are abundant in RA synovium?
macrophage and fibroblast cytokines
what is the role of IL-6?
mediate systemic effects
what is the role of neoangiogenesis?
to provide nutrients to hyperplastic synovium
how is bone destruction mediated in RA?
by osteoclasts that are activated by RANKL (produced in synovium) and fibroblast-like synoviocytes
name 2 genes which are implicated in susceptibility to RA?
class II major histocompatibility complex genes and PTPN22
when can increased serum levels of RFs and anti-CCP be seen?
years before onset of arthritis
name 2 therapeutic target cytokines?
TNF-alpha and IL-6
name 4 systemic effects secondary to uncontrolled inflammation due to RA?
vasculitis, nodules, scleritis, amyloidosis
name 5 potential systemic complications of RA?
2y fibromyalgia, anaemia, osteoporosis, fibrosis, 2y Sjorgen’s syndrome
