RA + Inflammation

Question 1

what enzyme is responsible for generating citrullinated proteins targeted by autoantibodies in RA?

Answer 1

peptidylarginine deiminases (PADs)

Question 2

name a cellular structure formed by neutrophils that contribute to immune activation in RA

Answer 2

neutrophil extracellular traps (NETs)

Question 3

what are the primary inflammatory cytokines involved in RA?

Answer 3

TNF-alpha, IL-6 and IL-1

Question 4

which genetic and epigenetic factors are implicated in RA development?

Answer 4

mutations and epigenetic modifications in genes that regulate the immune response

Question 5

what does FLS stand for?

Answer 5

Fibroblast-like Synoviocytes

Question 6

what role do FLS play in RA?

Answer 6

FLS contribute to joint inflammation and degradation through signaling pathways and metabolic changes

Question 7

which signalling pathway in FLS is commonly targeted in RA therapy?

Answer 7

NF-kB

Question 8

how is the metabolism of FLS altered in RA

Answer 8

FLS in RA exhibit increased glycolysis and altered lipid metabolism to support inflammation

Question 9

what type of drug is methotrexate and how is it classified in RA treatment?

Answer 9

conventional synthetic DMARD (csDMARD)

Question 10

what is the primary action of NSAIDs in RA management?

Answer 10

NSAIDs reduce pain and inflammation by inhibiting COX enzymes

Question 11

why are glucocorticoids used in RA, and what is a limitation of their use?

Answer 11

glucocorticoids suppress inflammation but have significant S/Es with long-term use

Question 12

what does DMARD stand for?

Answer 12

disease-modifying antirheumatic drugs

Question 13

what is a bDMARD?

Answer 13

biological DMARD

Question 14

what is the TNF-alpha hypothesis in RA?

Answer 14

it proposes that TNF-alpha is a key cytokine driving inflammation in RA

Question 15

name an early TNF-alpha inhibitor used in RA treatment

Answer 15

Etanercept

Question 16

how does adalimumab function in RA therapy?

Answer 16

adalimumab is a mAb that binds TNF-alpha, blocking its activity

Question 17

what is the difference between the variable regions of adalimumab and etanercept?

Answer 17

adalimumab uses human variable regions, while etanercept has both human and mouse variable regions

Question 18

what are the limitations of using TNF-alpha inhibitors in RA?

Answer 18

increased risk of infections and malignancies

Question 19

what is a tsDMARD?

Answer 19

targeted synthetic DMARD

Question 20

what class of drugs does Tofacitinib belong to and what pathway does it target?

Answer 20

it is a tsDMARD that targets the JAK/STAT pathway

Question 21

what are tsDMARDs designed to inhibit specifically in RA treatment?

Answer 21

specific molecular pathways involved in inflammation such as JAK/STAT

Question 22

how to tsDMARDs differ from csDMARDS?

Answer 22

tsDMARDs target specific intracellular pathways, whereas csDMARDs have broader, non-specific immunosuppressive effects

Question 23

which type of RA patients are tsDMARDs typically reserved for?

Answer 23

patients who do not respond adequately to csDMARDs and bDMARDs

Question 24

name a type of therapy currently being explored as a future treatment for RA

Answer 24

cell and gene therapies

Question 25

how might gene therapy be applied in RA treatment?

Answer 25

by modifying genes that regulate immune responses to reduce inflammation

Question 26

what advantage does cell therapy offer over traditional RA treatments?

Answer 26

it could provide a more targeted and long-lasting immune modulation

Question 27

what is the role of 5-AZA-CdR in experimental RA treatment?

Answer 27

it is an epigenetic drug that may reduce inflammation by altering DNA methylation

Question 28

what type of immune cells are primarily targeted by TNF-alpha inhibitors?

Answer 28

T cells and macrophages that produce TNF-alpha

Question 29

how does the presence of autoantibodies affect RA progression?

Answer 29

autoantibodies promote chronic inflammation and joint damage

Question 30

which cytokine is primarily responsible for activating T cells in RA?

Answer 30

IL-6

Question 31

what is the function of CD4+ T cells in RA pathology?

Answer 31

they promote inflammation by activating other immune cells

Question 32

what is the goal of RA pharmacotherapy?

Answer 32

to reduce inflammation, control symptoms, and prevent joint damage

Question 33

why might combination therapy be used in RA?

Answer 33

to enhance efficacy and reduce disease progression, often by combining csDMARDs and bDMARDs

Question 34

how does genetic variation influence patient response to RA drugs?

Answer 34

genetic variations can affect drug metabolism and response which influences effectiveness and side effects

Question 35

what role does epigenetic modification play in the development of RA?

Answer 35

epigenetic changes can activate genes associated with inflammation, contributing to RA pathology

Question 36

why is monitoring necessary during bDMARD therapy?

Answer 36

to assess efficacy and detect adverse effects like infections

Question 37

what makes TNF-alpha inhibitors less effective in some patients?

Answer 37

differences in individual immune responses and potential development of antibodies against the biologic agent

Question 38

how do NETs contribute to RA pathology?

Answer 38

NETs release autoantigens that activate the immune system and perpetuate inflammation

Question 39

what is the impact of cytokine release on joint health in RA?

Answer 39

cytokine release leads to chronic inflammation, which damages joint tissues and causes erosion

Question 40

describe a potential gene therapy target for RA

Answer 40

genes regulating TNF-alpha production or inflammatory cytokine pathways

Question 41

high might cellular metabolism be a therapeutic target in RA?

Answer 41

altering metabolic pathways in FLS can reduce their inflammatory activity and joint-damaging effects

Question 42

what does the presence of PADs in synovial fluid indicate?

Answer 42

it suggests citrullination of proteins, which can lead to the formation of autoantibodies

Question 43

how does Tofacitinib work at the molecular level in RA therapy?

Answer 43

it inhibits the JAK/STAT pathway, reducing inflammation by limiting cytokine signalling