RA Flashcards
RA is a chronic inflammatory disease affecting primarily
synovium
Epidemiology RA
female 30-50s
Etiology of RA
genetic + envrio
HLA-D4 and smoking are the big ones
= predispose person to auto Abs against type 2 collagen and fibrinogen
How does smoking contribute to the pathogenesis of RA? (potentially)
ok this might not be 100% right but I was piecing together info from the lecture and the textbook bc neither were very clear..
- Activates enzyme that converts arg to citrulline. Citrulline is deposited in synovium and is attached to collagen and fibrinogen. It is recognized as a foreign substance and immune response is mediated against it →inflammation in synovium → destruction of joint
- Also/Or smoking thought to cause citruallation: a process that modifies Ag (type II collagen and fibrinogen) to match the “shared epitope” of the HLA alleles
Ab to Fc portion of IgG
rheumatoid factor
What is the orignation of RF
bone marrow
Auto Ab most specific to RA
ACPA
predictor/assc with aggressive dz
high titers of RF and ACPA
cause mast cell and basophil degranulation
ACPA
systemic Ag that RA auto-Abs recognize
glucose phosphate isomerase
joint Ag tht RA auto-Abs recognize
type II collage
also fibrinogen, proteoglycans
How is the synovial lining altered in RA?
undergoes hyperplasia
FLS: invade and damage cartilafe by producing MMPs, serine proteases, cathepsins, aggrecanases
What is the shared epitope
5 aa sequence on Beta chain of HLA-D4 MHC class II haplotypes that correspond to an Ag that is anthrogenic (molecular mimic of type II collagen)
What infections are proposed to cause RA
mycobacterium, Parvo B19, MTB, EBV, retroviruses, enteric bacteria
What other dz are assc with having increased titers of RF
SLE, Sjogren’s, Hep B and C, HIV, and chronic inflammation, SBE
in synovium: create a toxic environment → cell damage → inflammation
ROS and nitrogen
cause cells to accumulate in synovium
Deficiencies in apoptosis
p53
provides nutrients to expanding synovium.
angiogenesis