CE L5 New therapies

Question 1

Limitations of current RA therapies (5)

Answer 1

Only treat the symptoms
Disease is progressive
Patients often do not respond
Serious s/e with long term use
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Question 2

Name the family of enzymes which are involved in joint destruction in RA?

Answer 2

Matrix metalloproteinases

Question 3

What do MMPs do? (2)

Answer 3

Degrade bone and cartilage

Promote angiogenesis

Question 4

MMPs increase what cytokine?

Answer 4

TNF

Question 5

What was Trocade?

Answer 5

Trialled for RA - didn’t work.

It was specific for collagenases.

Question 6

We are not moving towards more specific MMP inhibition for example

Answer 6

Gelatinase A

Question 7

Two examples of immunosuppressants
And what class are they?

Answer 7

Tacrolimus and cyclosporin

Fungal peptides

Question 8

Immunosuppressants do what? (3)

Answer 8

Selective effects of T lymphocytes
Prevents clonal expansion (IL2 and IL2R)
Builds immunophilins and inhibits gene transcription

Question 9

3 classes of anti inflammatory drugs that are used in RA?

Answer 9

omega 3
Type IV PDEIs
Cytotoxic agents

Question 10

What to type IV PDEIs do? Increase …… and suppress……

Answer 10

increase cAMP and suppress TNF translation

Question 11

two e.g. of cytotoxic agents

Answer 11

azathioprine and cyclophosphamide

Question 12

How does Omega 3 help?

Answer 12

high doses change AA metabolites to PGE3 and LTB5 - these are less inflammatory

Question 13

Name some alternative targets for RA treatment

- you don’t need to learn

Answer 13

Antilymphocyte immunoglobulin
5 lipoxygenase inhibitors
Oral ICE inhibitors
CLTA-4Ig
Anti cadherin 11
Anti IL6

Question 14

What is cadherin?

Answer 14

an adhesion molecule

Question 15

who produces IL17?

Answer 15

Activated type 17 T helper cells

Question 16

where is IL17 found?

Answer 16

inflammed joints

Question 17

What does IL17 synergise the effects of?

Answer 17

TNF

Question 18

Name some stuff that IL17 upregulates?

Answer 18

NFKB, MAPK, IL6

COX2 NO

Question 19

Name some supressor T cells that dampen down immune activation

Answer 19

CD4+
CD25+
FOX3

Question 20

Name 2 cytokines secreted by suppressor T cells

Answer 20

IL 10

TGF beta

Question 21

Why are modulatory APC of current interest?

Answer 21

(Antigen Presenting cells e.g. Dendritic cells) - trying to switch off the cells producing cytokines.

Question 22

What B cells are increased and decreased in RA?

Answer 22

B7-2 is increase

FcR is decreased

Question 23

How does alpha-TNF therapy affect B cells expression?

Answer 23

B7-2 expression is reduced

Question 24

What is Rituximab?

Answer 24

Chimeric monoclonal alpha-CD20

Question 25

What is Rituximab given with?

Answer 25

Methotrexate