what is rheumatoid arthritis?
immune-mediated inflammatory disease (autoimmune disease)
name the 2 types of synoviocytes in the synovial membrane
type A macrophages
type B fibroblasts
what is the function of the synovial membrane?
tight-junction forming resident lining of macrophages form a protective barrier for joint structures, when this disintegrates infiltration of inflammatory myeloid cells occur
what is the function of ACPA?
- induce activation of osteoclasts
- induce pain behaviour
what are osteoclasts?
the precursors that develop into immune cells
name the 3 stages of developing seropositive RA
- risk of developing RA; antibody production
- ACPA-associated disease; osteoclast activation and IL-8 production
- ACPA-positive RA; inflammation
describe the role of IL-12/Th1 in RA
p40 deficient; no disease
p35 and IFNy deficient; increased disease severity
describe the role of IL-23/Th17 in RA
IL-23 is required for the induction of disease, it regulates the inflammatory activity of autoantibodies via altering glycosylation
Th17 produces IL-17A
how is early RA diagnosed?
increased CCR6+ memory T cells producing IL-17A and TNFa
name 2 treatments for RA
- targetting IL-17 to neutralize Th17 activity
- TNF inhibitors
how can antibodies contribute to inflammation?
- by activating complement
- by binding to Fc-receptors on macrophages (activating and inhibiting)
name the 2 autoantibodies in RA
- rheumatoid factor (RF)
- antibodies against citrullinated protein antigens (ACPA)
name 2 targeted therapies for B cells in RA
rituximab; anti-CD20
tocilizumab; IL6 receptor antagonist
what are rheumatoid factors?
- autoantibodies directed against the Fc-part of IgG
- IgM, IgG and IgA
- are able to form large immune complexes
- role in the clearance of excess of immune complexes after infection
what are ACPAs?
general term to all antibodies directed against citrullinated epitopes
what are anti-CCP?
cyclic citrullinated peptide; artificial peptide containing citrullinated epitopes
what is citrullination?
arginine deimination, post-translational modification of the amino acid arginine into citrulline by peptidylarginine deiminases (PADs)
what is the difference between seropositive and seronegative?
seropositive is with autoantibodies and seronegative is without
what is fine specificity of ACPA and its hypothesis?
response against specific citrullinated proteins
hypothesis; fine specificity increases in time and after a critical mass has been reached, arthritis occurs
what are the 2 hypotheses about the development of RA?
1; ACPA-response does not change, the expression of certain citrullinated epitopes change
2; ACPA-response changes over time, expression of certain epitopes does not
what is the 4 roles of B cells in the pathogenesis of RA?
antigen presentation of T cells and antibody production, cytokine production and stimulation via cell-cell interaction
Name 2 inflammation markers
CRP and BSE
name 2 different DMARDs
- conventional DMARD; disease modifying anti-rheumatic drug (MTX, SASP, LEF, HCQ)
- biological DMARD; biological agents that target inflammatory cytokines or cells (monoclonal antibodies, natural antagonists, -mab/cept)
