Lecture 25 - Intro to RA

Question 1

There are more than ___different types of arthritis

Answer 1

There are more than 100 different types of arthritis

Question 2

IN adult caucasian populations _% will have RA

Answer 2

1%

Question 3

RA leads to …

Answer 3

Progressive disability
reduced life expectancy
Significant socioeconomic costs

Question 4

The Primary manifestation of RA is

Answer 4

Synovitis

erosion of bone cartilage, peri-articular strutures

Question 5

Genetic susceptibility + environmental facts leads to a

Answer 5

breakdown of immune tolerance (self-reactive antibody or T cells - autoimmune disease

Question 6

Genetic risk factors accounts for ___% of disease suseptabillity

Answer 6

50-60%

Question 7

The HLA class _ genes are most important in Ra

Answer 7

2

Question 8

what is HLA

Answer 8

Group of genes, exists on arm of chr. 6

divides in to 3 broad regions

Class 2 is of interest

Question 9

Which alleles in Class 2 of HLA are of interst?

Answer 9

DRB-1

Question 10

Citrulline is an

Answer 10

arthritogenic or (arthritis promoting gene)

they bind extremely well to the shared epitope of APC

Question 11

Citrulline can cause ___expression, which is used for RA diagnosis

Answer 11

Anti-citrillinated protein anibodies

Question 12

Shared epitope can influence _____selection of autoimmune T cells

Answer 12

Thymic

Question 13

Shared epitope is mimicked by which virus?

Answer 13

epstein barr virus

Question 14

Cohort with recent-onset undifferentiated (ACPA+) arthritis, progression to RA occurred regardless of ____-_____

Answer 14

HLA-DR genotype

Question 15

Maternal cells of SE-expressing women persist in their children’s circulation throughout adulthood, which confers

Answer 15

increased RA risk

Question 16

THere are non-HLA genes conferring RA risk

they are?

Answer 16

PTPN22
PAD14

among others….

Question 17

True or False

Epigenetic risk factors for RA may be heritable

Answer 17

true

DNA methylation - can have unusualness in RA

also, microRNAs

Question 18

oestrogen exposure - B cells that produce autoantibodies are ___ resistant to apoptosis

Answer 18

more

Question 19

in the presense of oestrogen Fibroblast-like synoviocytes (FLS) lead to an increase in ______

Answer 19

metalloproteinases

Question 20

In preganancy more than 3/4 pateints RA ___

Answer 20

improves

Question 21

True or False

RA can go into remission in the 3rd trimester of pregnancy

Answer 21

true

Question 22

What is Citrullination?

Answer 22

post-translational conversion of the AA Argginine (R) to citrulline by PAD1 enzymes (Peotidyl-arginine deiminase)

Neoepitopes serve as targets for autoimmunity

Question 23

Citrulline binds _____ _____ more avidly

Answer 23

shared epitope

Question 24

True or False

Induction of PAD1 expression and peptide citrullination is specific the joint or RA

Answer 24

False

Occurs in many different settings of tissue stress/inflammation

Question 25

In humans there are _isoforms of PAD1 enzymes

Answer 25

4

Question 26

What are environmental factors?

Answer 26

pollution smoking - involved in citrullination process Bronchial stress Infections TLR activation (increase PAD enzyme)

Question 27

What will RA patients clinically present with?

Answer 27

Morning stiffness Pain Swelling Symmetrical distribution

Question 28

What are the most commonly affected joints?

Answer 28

Metacarpophalangeal proximal interphelangeal Wrist Metatarspophalangeal

Question 29

RA tends to happen in ____ pateints

Answer 29

younger

Question 30

true or FalseOsteoarthritis is frequently asymmetrical

Answer 30

true

Question 31

RA can involve what extra-articular manifestations?

Answer 31

``` Pulmonary -effusion Ocular Vasculitis Neurological Cardiovascular cutaneous Haematologic Malignancy ```

Question 32

What is the Rheumatoid Factor (RF)?

Answer 32

High-affinity autoantibody against the Fc portion of IgG

Question 33

True or False RF develops prior to RA onset

Answer 33

true

Question 34

The anti0cyclic citrullinated peptide assay (CCP) can detect..

Answer 34

Anti-citrullinated protein antibdies (ACPA)

Question 35

About __% of pateints with RA test positive to RF test

Answer 35

70% - senesitivity

Question 36

The specificity for ACPA is __%

Answer 36

95%

Question 37

A person is __x more likely to test postivie for ACPA if they have RA, compared to someone who doesn't

Answer 37

14x

Question 38

So the two subsets of RA are

Answer 38

seropositive - RF or ACPA positive Seronegative - RF or ACPA negative

Question 39

seropositive patients tend to have more ____ disease

Answer 39

aggressive

Question 40

DAS calculator: below 2.6 is

Answer 40

RA remission

Question 41

DAS of over 5.1 is..

Answer 41

High disease activity

Question 42

subclinical inflammation can be best seen by

Answer 42

MRI