hIVIG review. Spurlock and Prittie. 2011. JVECC.

Question 1

What is the main immunoglobulin in hIVIG?

Answer 1

IgG (>90% intact)

trace amounts of IgA, IgM, CD4, CD8, human leukocyte antigen molecules

Question 2

is hIVIG acidic or alkaline?

Answer 2

acidic
lower pH deters infectious agents and prevents aggregation

Question 3

What is the half-life of hIVIG in dogs?

Answer 3

7-9 days

Question 4

What are the 5 mechanisms by which hIVIG causes immunosuppression?

Answer 4

• blocks Fc receptors
• reduces cytokine synthesis
• inhibits complement
• facilitates removal of pathogenic autoantibodies
• mediates Fas-FasL binding

Question 5

what cells in the dog has human IgG been shown to effectively bind to

Answer 5

canine monocytes and lymphocytes

Question 6

explain the mechanism of action of hIVIG via Fc receptors

Answer 6

normally Fc receptors on cell membranes bind to antigen-antibody complexes which leads to antibody-mediated phagocytosis

binding of human IgG to the Fc receptors blocks this phagocytosis -> decreases tissue damage

Question 7

how does hIVIG facilitate autoantibody removal

Answer 7

postulated to directly bind to abnormal host antibodies -> stimulate removal

does not work as well in companion animals –> interspecies antibodies bind poorly

Question 8

How does hIVIG reduce tissue damage through the complement system

Answer 8

normally IgG-antigen complex binds to circulating complement -> initiates cascade, leading to apoptosis
hIVIG -> blocks this pathway by binding to C3 and C4 complement fragments –> cannot generate MAC –> limits tissue damage

Question 9

what mechanism of hIVIG is the presumed reason for its success in dermatologic conditions?

Answer 9

blockade of Fas-FasL complex formation -> inhibits keratinocyte apoptosis

Question 10

Which of the 5 mechanisms of action of hIVIG is targeted for its use in IMHA

Answer 10

Fc receptor blockage -> happens immediately and may help stabilize patient until other immmunomodulatory drugs start to work

Question 11

What is the current evidence supporting hIVIG use in dogs with IMHA?

Answer 11

• lack of evidence, randomized controled,blinded trial of 28 dogs did not show significant difference
• current evidence cannot justify use

Whelan et al

Question 12

What is the current evidence supporting hIVIG use in dogs with ITP?

Answer 12

Bianco et al, Randomized, controlled, blinded
glucocorticoids + hIVIG vs. glucocorticoids alone
faster resolution of thrombocytopenia, and earlier discharge from hospital

results compare to Rosanzki et al study of glucocorticoids versus glucocorticoids + vincristine though
need vincristine vs hIVIG to justify use

Question 13

What is the pathogenesis of myasthenia gravis?

Answer 13

immune-mediated neuromuscular disorder
autoantibody mediated destruction of acetylcholine receptors in the postsynaptic neuromuscular junction
-> weakness

Question 14

List the adverse effects of hIVIG

Answer 14

• acute hypersensitivity/transfusion reactions
• thromboembolism
• renal failure
• hypotension
• aseptic meningitis
• fluid overload

Question 15

What is the presumed underlying mechanism of transfusion reactions from hIVIG?

Answer 15

IgG aggregation and complement activation
type I hypersensitivity reactions

Question 16

What implementations have reduced occurence of hypersensitivity reactions from hIVIG?

Answer 16

• removal of aggregates
• slow transfusion rates
• hIVIG preparations with lower IgA levels

Question 17

What are the 4 mechanisms/properties by which hIVIG causes hypercoagulability in patients?

Answer 17

• increased platelet numbers and platelet activation
• contains prothrombotic factor Xa
• hyperosmolarity
• hyperviscosity

Question 18

How does hyperviscosity cause thromboembolic disease?

Answer 18

via impediment of capillary flow

Question 19

How does hIVIG primarily cause renal injury?

Answer 19

secondary to osmotic damage to the proximal tubules

Question 20

what component of hIVIG is implicated to cause renal injury?

Answer 20

sucrose - agent used to stabilize hIVIG preparations

alternative stabilizers are albumin, glucose, maltose, glycine, D-sorbitol

Question 21

How does an type III allergic reaction lead to renal injury?

Answer 21

allergen-IgG complex precipitaiton in renal tissues leads to inflammation via complement fixation -> glomerulonephritis develops

Question 22

Are larger or smaller donor pools of hIVIG saver for patient?

Answer 22

smaller donor pools -> the larger the donor poor the higher the risk of igG dimerization and subsequent complement activation -> leads to hypotensive events

Question 23

Does acidic or alkaline pH reduce the risk of IgG dimerization?

Answer 23

low pH (acidic)

Question 24

At what rate should hIVIG be started and what is the maximum rate for administration of hIVIG?

Answer 24

start at 0.1 mL/kg/min
maximum rate 0.08 mL/kg/,in

Question 25

How long until onset of Fc blockade after administering hIVIG?

Answer 25

3 days
rapid response in dogs has been reported within 24-48 hours

Question 26

List 6 conditions hIVIG has been previously evaluated for

Answer 26

• IMHA
• ITP
• Evans Syndrome
• Cutaneous autoimmune disease
• MG
• SARDS