Lecture 25 - Intro to RA Flashcards
There are more than ___different types of arthritis
There are more than 100 different types of arthritis
IN adult caucasian populations _% will have RA
1%
RA leads to …
Progressive disability
reduced life expectancy
Significant socioeconomic costs
The Primary manifestation of RA is
Synovitis
erosion of bone cartilage, peri-articular strutures
Genetic susceptibility + environmental facts leads to a
breakdown of immune tolerance (self-reactive antibody or T cells - autoimmune disease
Genetic risk factors accounts for ___% of disease suseptabillity
50-60%
The HLA class _ genes are most important in Ra
2
what is HLA
Group of genes, exists on arm of chr. 6
divides in to 3 broad regions
Class 2 is of interest
Which alleles in Class 2 of HLA are of interst?
DRB-1
Citrulline is an
arthritogenic or (arthritis promoting gene)
they bind extremely well to the shared epitope of APC
Citrulline can cause ___expression, which is used for RA diagnosis
Anti-citrillinated protein anibodies
Shared epitope can influence _____selection of autoimmune T cells
Thymic
Shared epitope is mimicked by which virus?
epstein barr virus
Cohort with recent-onset undifferentiated (ACPA+) arthritis, progression to RA occurred regardless of ____-_____
HLA-DR genotype
Maternal cells of SE-expressing women persist in their children’s circulation throughout adulthood, which confers
increased RA risk
THere are non-HLA genes conferring RA risk
they are?
PTPN22
PAD14
among others….
True or False
Epigenetic risk factors for RA may be heritable
true
DNA methylation - can have unusualness in RA
also, microRNAs
oestrogen exposure - B cells that produce autoantibodies are ___ resistant to apoptosis
more
in the presense of oestrogen Fibroblast-like synoviocytes (FLS) lead to an increase in ______
metalloproteinases
In preganancy more than 3/4 pateints RA ___
improves
True or False
RA can go into remission in the 3rd trimester of pregnancy
true
What is Citrullination?
post-translational conversion of the AA Argginine (R) to citrulline by PAD1 enzymes (Peotidyl-arginine deiminase)
Neoepitopes serve as targets for autoimmunity
Citrulline binds _____ _____ more avidly
shared epitope
True or False
Induction of PAD1 expression and peptide citrullination is specific the joint or RA
False
Occurs in many different settings of tissue stress/inflammation