RA

Question 1

RA is a chronic inflammatory disease affecting primarily

Answer 1

synovium

Question 2

Epidemiology RA

Answer 2

female 30-50s

Question 3

Etiology of RA

Answer 3

genetic + envrio

HLA-D4 and smoking are the big ones
= predispose person to auto Abs against type 2 collagen and fibrinogen

Question 4

How does smoking contribute to the pathogenesis of RA? (potentially)

Answer 4

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

Question 5

Ab to Fc portion of IgG

Answer 5

rheumatoid factor

Question 6

What is the orignation of RF

Answer 6

bone marrow

Question 7

Auto Ab most specific to RA

Answer 7

ACPA

Question 8

predictor/assc with aggressive dz

Answer 8

high titers of RF and ACPA

Question 9

cause mast cell and basophil degranulation

Answer 9

ACPA

Question 10

systemic Ag that RA auto-Abs recognize

Answer 10

glucose phosphate isomerase

Question 11

joint Ag tht RA auto-Abs recognize

Answer 11

type II collage

also fibrinogen, proteoglycans

Question 12

How is the synovial lining altered in RA?

Answer 12

undergoes hyperplasia

FLS: invade and damage cartilafe by producing MMPs, serine proteases, cathepsins, aggrecanases

Question 13

What is the shared epitope

Answer 13

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)

Question 14

What infections are proposed to cause RA

Answer 14

mycobacterium, Parvo B19, MTB, EBV, retroviruses, enteric bacteria

Question 15

What other dz are assc with having increased titers of RF

Answer 15

SLE, Sjogren’s, Hep B and C, HIV, and chronic inflammation, SBE

Question 16

in synovium: create a toxic environment → cell damage → inflammation

Answer 16

ROS and nitrogen

Question 17

cause cells to accumulate in synovium

Answer 17

Deficiencies in apoptosis

p53

Question 18

provides nutrients to expanding synovium.

Answer 18

angiogenesis

Question 19

what stimulates angiogenesis

Answer 19

IL-8, FGF, and VEGF

Question 20

expressesa adhesion molecules that guide circulating cells into the joint under the influence of chemoattractants

Answer 20

Microvascular endothelium in the synovium

Question 21

What cells are found in the synovial effusions of RA pts

Answer 21

neutrophils and mononuclear cells

Question 22

Why do COX -2 inhib work as therapy for RA

Answer 22

prostaglandins and LTs are found in synovial effusions

Question 23

What are the cellular origins of the cytokines found in synovial effusions?

Answer 23

macrophages, fibroblasts > T cells

Question 24

the key inflammatory mediator in RA

Answer 24

TNF-a

Question 25

Cytokines in Synovium

Answer 25

``` TNF-a IL-1, 6, 8, 15, 17, 18, 33, 10 GM-CSF INF-gamma TGF-B FGF ```

Question 26

cytokines that activate chondrocytes and osteoclasts → joint destruction

Answer 26

TNF-a, IL-1, 6, and 8 | IL-17

Question 27

cytokines that Activate MMPs and release prostaglandins

Answer 27

TGF-B and FGF

Question 28

activates osteoclasts, chondrocytes, macrophages, fibroblasts

Answer 28

IL-17

Question 29

cytokines secreted by T cells

Answer 29

INF-gamma and IL-17

Question 30

IL-17 activates

Answer 30

osteoclasts, chondrocytes, macrophages, fibroblasts

Question 31

What are targets for RA therapy that would control cytokine signaling

Answer 31

``` NFkB MAP kinase AP-1 JAK Syk ```

Question 32

What do synovial lining cells produce that contibute to bone destruction

Answer 32

MMPs, serine proteases, cathepsins, aggrecanases

Question 33

What mediates cartialge and bone destuction in RA

Answer 33

synovial lining cells by secreting MMPs, serine proteases, cathepsins, aggrecanases osteoclasts (activ by RANKL (<--IL-17) Pannus (composed of macrophages and mesenchymal cells)

Question 34

invasive tissue of the synovium What cells make it up

Answer 34

pannus macrophages and mesenchymal cells

Question 35

systemic symptoms assc with RA

Answer 35

Fatigue, anorexia, weight loss, weakness, generalized aching and stiffness, low grade fever

Question 36

Articular presentation of RA

Answer 36

morning stiffness > 30 mins swelling, warmth, and erythema around joint atrophy of muscles +/- flexion contractures

Question 37

What joints are most characteristically involved in RA

Answer 37

wrist and proximal hand (MCP and PIP)

Question 38

What finding is seen at MCP

Answer 38

ulnar deviation

Question 39

What finding is seen at the PIP? DIP?

Answer 39

Swan-neck (PIP) and Boutonniere deformities (DIP)

Question 40

What finding is seen at the wrist?

Answer 40

Volar subluxation with radial-ward rotation

Question 41

describe the pattern of joint involvement in RA

Answer 41

Mono or oligio → poly and SYMMETRICAL

Question 42

Why are flexion contractures seen in RA?

Answer 42

Fibrosis and tightening of tissues due to chronic inflammation *Knee, hip, elbow

Question 43

Describe the synovial findings in RA

Answer 43

* Exudative * Yellow * Elevated WBC * Decreased viscosity (due to proteases that eat up HA)

Question 44

joints invovled in RA

Answer 44

knee, hip, elbows, shoulder, wrist, hand

Question 45

Extra articular manifestations of RA

Answer 45

RA has a RIPPLE effect throughout the body ``` Rheum nodules (skin, lung, heart valves) Interstitial fibrosis Palpable purpura (vasculitis) Pericarditis, PLeuritis Erosion of the Eyes, Entrapment (Nerve) syndromes ``` + dry eyes and mouth

Question 46

activate complement and IgE

Answer 46

ACPAs