Rheumatoid Arthritis-Hudig Flashcards
WHat is rheumatoid arthritis defined as?
synovitis in 1 or more joints
score greater than 6
What is the scoring system for arthritis?
Score = or > 6 for
Number and sites of the involved joints, 0-5 points
Serology, 0-3 points
Elevated acute phase response (APR), 0-1 points
Duration of symptoms, 0-1points
What are some lab indicators of rheumatoid arthritis?
RA synovial lymphocytes >2000
anti-citrullinated peptide antibody
synovial fluid turbid, yellow, neutrophils present. No crystals!
What are some systemic manifestations of rheumatoid arthritis?
generalized fatigue
low grade fever
C-reactive protein
**maybe vasculitis, pleurisy, pericarditis
What are the 4 criteria the trust be met for autoimmunity?
auto antigens involved in the disease
anti-self immunity with immune mediators of damage
immunogenetics & therpaeutics
What are some of the microscopic features of rheumatoid arthritis?
finger-like protrusions into synovium **they are inflamed fibrovascular stroma covered in epithelial cells hyperplasia of synoviocytes inflammatory cells present
What are the 4 types of immune cells involved in rheumatoid arthritis?
CD4 TH1 CD4 TH17 CD4 Treg NK cells Note: CD8 not involved
What are the 5 major cell types found in an RA lesion?
Dendritic Cells (APC) T cells B Cells Macrophages Neutrophils
Describe the process that begins with APC in rheumatic lesion & ends with recruitment of neutrophils.
APC bind antigen. Activates CD4 THO Cell. Secretes IL6 & TGF beta Activates CD4 TH17 Releases IL-17 IL-17 binds fibroblasts. They release CXCL2 & CXCL8 Neutrophils recruited!
Which T cells are found in rheumatic lesions?
CD4 TH1
CD4 TH17
CD4 T reg
What are some important antibodies produced by B cells?
RA
anti-citrullinated peptide antibody
Describe the process that begins with macrophages & ends with activated osteoclasts.
CD4 activates macrophages.
Cytokines released.
Fibroblasts activated & they release MMP & RANK.
Osteoclasts active.
What are the 4 major cytokines seen in rheumatic lesions?
TNF alpha
IL-1
IL-6
IL-17
What is the process of citrullination?
post-translational modification that converts arginine into citrulline
carried out by intracellular enzyme: PAD
What is an important protein that gets citrullinated in rheumatoid arthritis?
Vimentin, also collagen
intermediate filament protein
gets citrullinated during cell death or inflammation
What is the sensitivity & specificity of the APCA test for rheumatoid arthritis?
sens: 70%
Spec: 99%
What is the structure of rheumatoid factor?
IgM or IgA antibody against Fc portion of IgG
What is the sensitivity & specificity for testing RF?
sens: 70%
spec: low b/c also seen in lupus
What is epitope spreading?
immune reaction changes from targeting one epitope to multiple epitopes
seems to happen with citrullination in RA
Which cytokines do glucocorticoids reduce when treating RA?
IL-1
TNFalpha
Which RA treatment reduces T & B cell expansion?
methotrexate
Biologic DMARDs block which cytokines usu?
TNFalpha
IL-6
Why is it good to block IL-6 with a biologic DMARD?
then you don’t get TH17 activation & secretion of IL-17 & recruitment of neutrophils
