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
In humans there are _isoforms of PAD1 enzymes
4
What are environmental factors?
pollution
smoking - involved in citrullination process
Bronchial stress
Infections
TLR activation (increase PAD enzyme)
What will RA patients clinically present with?
Morning stiffness
Pain
Swelling
Symmetrical distribution
What are the most commonly affected joints?
Metacarpophalangeal
proximal interphelangeal
Wrist
Metatarspophalangeal
RA tends to happen in ____ pateints
younger
true or FalseOsteoarthritis is frequently asymmetrical
true
RA can involve what extra-articular manifestations?
Pulmonary -effusion Ocular Vasculitis Neurological Cardiovascular cutaneous Haematologic Malignancy
What is the Rheumatoid Factor (RF)?
High-affinity autoantibody against the Fc portion of IgG
True or False
RF develops prior to RA onset
true
The anti0cyclic citrullinated peptide assay (CCP) can detect..
Anti-citrullinated protein antibdies (ACPA)
About __% of pateints with RA test positive to RF test
70% - senesitivity
The specificity for ACPA is __%
95%
A person is __x more likely to test postivie for ACPA if they have RA, compared to someone who doesn’t
14x
So the two subsets of RA are
seropositive - RF or ACPA positive
Seronegative - RF or ACPA negative
seropositive patients tend to have more ____ disease
aggressive
DAS calculator:
below 2.6 is
RA remission
DAS of over 5.1 is..
High disease activity
subclinical inflammation can be best seen by
MRI
