Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Module 204 MSK & Immune system > Rheumatoid arthritis symposium > Flashcards

Rheumatoid arthritis symposium Flashcards

1
Q

What is autoimmunity?

A

Immune response to self-antigens

Represents a breakdown of immunological tolerance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the consequence of chronic cytokine release?

A

Tissue destruction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is rheumatoid arthritis?

A

Inflammation of synovial joints

Systemic inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Who is affected by RA?

A

1% of population
3X more common in women
Diagnosis common at 40-50 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are some long-term complications of rheumatoid arthritis?

A 
Acute-phase response in liver
Production of free fatty acids and adipoctokines leading to insulin resistance
Low bone mineral density and fractures
Low stress tolerance and depression
Atherogenesis, MI, stroke
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the pattern of joint damage in RA

A

Usually multiple joints in a symmetrical fashion
Morning stiffness
Swelling, heat, redness, pain
Loss of funciton

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is synovitis?

A

Swelling over extensor tendons, wrist and MCP joints

Synovium hyperplasia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe synovial fibroblasts in synovitis

A

Reduced apoptosis
Enhanced anchorage
Upregulated adhesion molecules
Increased proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the pathology of rheumatoid arthritis?

A 
Pannus
Synovial fluid rich in neutrophils
Synovitis
Cartilage erosion
Bone erosion
Cartilage loss
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is pannus?

A

Inflammed synovial membrane due to cells infiltrating from blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the composition of synovial tissue?

A

Macrophages - 40%
Fibroblast and endothelial cells -10-15%
T-lymphoctes - 40%
B lymphocytes and plasma cells - 5%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the key populations of T cells in RA synovial?

A

Th17 and Th1 cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is IL-17 known to do?

A

Activate synovial fibroblasts and osteoclasts which remove bone
Favour cartilage resorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe B-cells in RA

A

B cells form diffuse or follicular infiltrates in synovium

Produce cytokines and are important for antigen presentation e.g. IL-6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does monoclonal anti-CD20 do to B cells?

A

Depletes B-cells and is an effective treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe cartilage erosion

A

Fibroblasts make matrix metalloproteases which break down collagen network in cartilage
Chondrocytes undergo apoptosis
Fibroblasts adhere to and invade cartilage leading to biochemical dysfunction and joint space narrowing.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What cytokines produce osteoclast differentiation and activation?

A 
IL-17
RANKL
TNF-alpha
IL-1
IL-6
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What percentage of patients are affected by bone erosion within 1 year of diagnosis?

A

80%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the clinical markers of RA?

A

Elevated ESR
Elevated CRP
Rheumatoid factor
Cyclic citrullinated peptide antibodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is rheumatoid factor?

A

Made by B cells and directed against Fc portion of another antibody to form immune complex
2 varies: IgM or IgG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Why is rheumatoid factor not that useful for diagnosis of RA?

A

Not specific for RA
Also present in other autoimmune diseases and in some healthy individuals
Some RA patients are seronegative
Levels don’t correlate with disease activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe use of CCP antibody for diagnosis of RA

A

Antibodies directed against CCP found in 60-70% of patients with RA
Rarely found in healthy people who don’t go on to develop RA
Detectable in blood many years before disease onset
Anti-CCP positive RA has a more aggressive clinical course of disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is citrullination?

A

Process of replacing protein arginine residues with citrulline residues
Occurs normally in body but if it occurs on an unusual part of the protein they may be recognised as foreign leading to antibody response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What citrullinated self-proteins are most likely in RA?

A 
alpha-enolase
Keratin
Fibrinogen
Fibronectin
Collagen
Vimentin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What are the possible mechanisms for anti-CCP antibodies enhancing development and severity of inflammation when mild synovitis is already present?
Activation of inflammatory cells by anti-CCP immune complexes Anti-CCP mediated neutrophil cell death producing NETs Direct binding of anti-CCPs to drive osteoclastogenesis
26
Describe the incidence of RA worldwide
1% Less common in South America and asia high incidence in North Americans in north america
27
What polymorphisms are associated with RA?
``` HLA-DRB1 SE PTPN22 CTLA4 STAT4 TRAF1 ```
28
What is HLA-DRB1 SE?
Human leucocyte antigen
29
What is PTPN22?
Protein tyrosine phosphatase 22 which regulates T-cell activation
30
What is CTLA4?
Co-stimulation suppressor that regulates interactions between T cells and APCs
31
What is STAT4?
Transducer of cytokine signals that regulate proliferation, survival and differentiation of lymphocytes
32
What is TRAF1?
Regulator of TNF-alpha receptor superfamily signalling
33
Describe the incidence of RA in twins
Monozygotic twins: 12-15% Dizygotic twins: 3-5% Suggests there is a genetic component but it is only weak
34
Describe the influence of hormones on developing RA
Testosterone considered protective against autoimmune diseases Risk of developing RA is increased during period just after giving birth RA patients often experience remission during pregnancy Risk of developing RA after menopause isn't influence by HRT
35
Describe the influence of smoking on developing RA
Heavy smoking increases risk of RA among people with susceptibility genes of HLA-DR4 alleles 2TCDD in cigarette smoke activates synovial fibroblasts which induce pro-inflammatory cytokines
36
Describe the suggestion of an infectious trigger of RA
Evidence is hard to find as infection may no longer be present once disease is established Bacterial components identified in joint tissue in both RA and healthy joint tissue
37
Give examples of infections that could trigger RA
``` Human parvovirus B19 Human retrovirus 5 Alphaviruses Hepatitis Chronic hepatitis C virus Epstein-Barr virus Mycoplasma E.coli Rubella virus Porphyromonas gingivitis ```
38
What are the 2 groups of pharmacological therapies for RA?
Anti-inflammatory drugs which provide symptom relief | Disease-modifying anti rheumatic drugs which slow clinical and radiographic progression of RA
39
What are some synthetic agents of DMARDs?
Methotrexate Sulfasalazine Hydroxychloroquine Leflunomide
40
What are some non-selective COX 1/2 inhibitors?
Aspirin Ibuprofen Diclofenac
41
Give an example of an NSAID COX-2 selective inhibitor
Celecoxib
42
What are the 2 types of anti-inflammatory drugs used?
NSAIDs | Steroid anti-inflammatory drugs, immunosuppressants
43
Give examples of steroids used
Prednisolone Depomedrone Triamcinolone
44
Why should long-term use of steroids be avoided?
Due to risk of infections and osteoporosis
45
What is the mechanism of methotrexate?
``` Inhibits cell proliferation Increases adenosine level Reduces production of polyamines Induces apoptosis of activated CD4 and CD8 T-cells Reduces inflammation ```
46
What are the 2 components of sulfasalazine?
Sulfapyridine | 5-amino salicylic acid
47
What is hydroxychloroquine used to treat?
Malaria | SLE
48
What is a possible mechanism of hydroxychloroquine?
Increases lysosomal pH
49
What is the mechanism of leflunomid?
Lymphocyte inhibitor Inhibits de novo pyrimidine synthesis Most effective in reducing B-cell populations (also has an effect on T-cells)
50
Describe DMARD combination therapy
More effective than single drug without extra side effects
51
What is the most effective DMARD combination?
MTX Sulfasalazine Hydroxychloroquine
52
What are the adverse effects of synthetic DMARDs?
``` Nausea Loss of appetite Diarrhoea Rash, allergic reaction Headache Hair loss Risk of infections Hepatotoxicity Kidney toxicity ```
53
What is TNF blockade used to treat?
RA Crohn's disease Ankylosing spondylitis Psoriasis
54
When is biological therapy recommended?
If patient failed to respond to at least 2 standard DMARDs | RA disease activity score measured ≥5 on 2 or more occasions
55
Give examples of TNF blockers
``` Etanercept Infliximab Adalimumab Certolizumab pegol Golimumab ```
56
What does Infliximab do?
Neutralises free, membrane and receptor bound TNA-alpha leading to antibody dependent cell-mediated cytotoxicity
57
What is infliximab also used for?
Crohn's disease UC Plaque psoriasis Ankylosing spondylitis
58
What does Etanercept do?
Binds free and membrane bound TNF reducing accessible TNF
59
What is etanercept also used for?
Juvenile idiopathic arthritis Plaque psoriasis Psoriatic arthritis Ankylosing spondylitis
60
What is adalimumab also used for?
``` Juvenile idiopathic arthritis Plaque psoriasis Psoriatic arthritis Ankylosing spondylitis Crohn's disease ```
61
What is golimumab also used in?
Psoriatic arthritis | Ankylosing spondylitis
62
What should patients be screened for before starting TNF therapy?
``` History of TB Multiple sclerosis Recurrent infections Leg ulcers Past history of cancer ```
63
What is rituximab?
Monoclonal antibody against B cells
64
How does rituximab work?
Depletes B cells Opsonises B cells which are attacked and killed via: - complement mediated cytotoxicity - antibody dependent cell-mediated cytotoxicity - apoptosis
65
What is rituximab also used to treat?
SLE
66
What is abatacept?
T-cell co stimulation blocker
67
How does abatacept work?
T-cell co stimulation blocker which increases threshold for T-cell activation Competitive inhibitor of Cd28 Suppresses proliferation of synovial recirculating T cells Reduces level of inflammatory mediators
68
What is tociluzimab?
IL-6R blocker
69
What is tociluzimab also used in?
Systemic juvenile idiopathic arthritis
70
What is anakinra?
IL-1R antagonist | Recombinant IL-1ra
71
How does anakinra work in RA?
Reduces bone erosion Decreases osteoclast production Blocks IL-1 induced MMP release from synovial cells
72
What are the adverse effects of biological therapies?
``` Increased risk of infections Nausea Headache Hypertension Allergic reactions ```
73
When are biological therapies contraindicated?
Pregnancy | Breastfeeding

Module 204 MSK & Immune system (44 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions