IVIG

Question 1

What does the IVIG contain (Spurlock, 2020)

Answer 1

-90% IgG
-traces: IgA, IgM, CD8, CD4 and leukocyte antigen

+ altered pH (to decerase bacterial contamination)

Question 2

What is the half life of IVIG?

Answer 2

-human: 21-33 days
-canine: 7-9 days

Question 3

By wich mechanisms do IVIG modulates immune system (Spurlock, 2020)

Answer 3

1. Fc receptor disruption
2. Pathologic autoAb neutralisation
3. Complement inhibition
4. Fas-FasL binding interference
5. Cytokine syntesis downregulation

Question 4

Where are Fc receptors found (Spurlock, 2020)

Answer 4

1. neutrophils
2. NK cells
3. macrophages
4. eosinophils
5. Mast cells
6. platelets

Question 5

How does IVIG block the Fc receptor?

Answer 5

-IVIG blocks transient Fc receptors, interferes with Ag presentation and downregulates the immune response
+IVIG initiates self-inhibition in inflammatory cells ( in presence of IVIG macrophages upregulate inhibitory receptors, which block FcR normally activated by immune complexes /dont release inflammatory mediators)

(Ab-Ag complex bind to Fc receptor and initiate phagocytosis)

Question 6

Within what time frame IVIG works in humans and dogs?

Answer 6

-in humans- Fc blockade is conc dependent and immediate - clinical effects within 3 days
-canine- within 24-48 h

Question 7

How does the autoAb neutralization works with IVIG (Spurlock, 2020)

Answer 7

-anti-idiotype Ab in hIVIG solutions- bind both Ag binding sites and non-binding site idiotypes on B cell Ig or circulating autoAb
-via this mech- IVIG can help regulate immune response by neutralising pathogenic autoAb

Question 8

Why is autoAb neutralization less effective in canine than in humans (Spurlock, 2020)

Answer 8

-because interspecies Ab binds poorly and rarely yields anti-idiotypic Ab

Question 9

What is the MOA of IVIG and complement inhibition?

Answer 9

-transfused Ig binds C3b and C4b
- subsequently inhibits generation of MAC (C5b-C9)
-prevents complement -Ig interaction and limits tissue damage

Question 10

To wich family Fas receptors belong?

Answer 10

TNF superfamiliy

Question 11

How does the IVIG block FAS-FASL mediation?

Answer 11

-blocks their interaction and prevents epidermal apoptosis
-they promote proinflammatory cytokines

Question 12

How does the IVIG downregulates cytokines?

Answer 12

-in the presence of IVIG , mononuclear cells and activated T cell produce less proinflammatory cytokines (IL-1, TNF-beta, INF-gamma) in response to lipopolysaccharide or bacterial superantigens
-the same cells produce antiinflammatory cytokine- IL-1 R anatagonis

Question 12

What are other immunomodulatory effects of IVIG?

Answer 12

-modulate adhension molecules, B and T cells
-modifications of innate and adaptive immunity
-dependant on dose or specific inflammatory conditions
-BUT effects are synergistic, and not mutually exclusive

Question 13

For wich conditions is hIVIG beeing used in vet med?

Answer 13

1. IMHA
2. ITP
3. Evans syndrome
4. Cutaneous autoimmune disease-EM (cat), SJS, TEN, PF
5. MG
6. Sudden acquired retinal degeneration syndrome

Question 14

Which drug is recommened in refractory ITP?

Answer 14

vincristine

Question 15

What are the dosages used in cutaneous diseases ?

Answer 15

1 g/kg over 4 h for 2 consecutive days

= 0.5-2.2 g/kg
-start slow at 0.01 mL/kg/min
-increase over 30-60 min
-max 0.8 mL/kg/min
-over 4 to 8 h

-reaction: stop +adminiter antihistamines

Question 16

What are the most common complications in human and vet medicine?

Answer 16

-people 5-15 %
-hypersensitiovity reactions- especially in dogs XENOPROTEIN
-thromboembiolism
-renail failure
-hypotension
-asepctic meningitis
-intravascular fluid overload
-transient neutropenia
-serum sickness

Question 16

What is the most common complication of hIVIG?

Answer 16

1. Acute hypersensitivity /anaphylaxis
   -rate of administration is correlated with complication rate
   -start slow then incerase
   -signs often reslove after slowing or temporarly disoctinuiting
2. type III hypersensitivity

Question 17

What are the most common symptoms of acute hypersnitivity of hIVIG?

Answer 17

-pyrexia, flushing, facial edema, tachycardia, vomiting, diarrhoea
-dysthythmias, dyspnea, hypotension, seizures
-anaphylaxis

Question 18

With type III hypersensitivity, what are symtoms and is it documented in canines?

Answer 18

-Ag-Ab complex deposition in renal basement membrane and glomerulonephritis
-NOT

Question 19

How does hIVIG promotes thromboembolic disease?

Answer 19

-because it stimulates inflammation, promotes hyper coagulability
-activates platelets
-especially be careful in IMHA (prothrombitic condition) - pretreatment with antithrombotic therapy
+ the hIVIG is a hyperosmolar fluid

Question 20

What is patomechanims of renal failure in hIVIG?

Answer 20

-sucrose is used as a stabilizer in hIVIG preparations
= cause osmotic damage to prox tubules , cellular swelling, tubular occlusion, cytoplasmic vacuolisation
-azotemina- within 5 days (can be transient)
-also available sucrose free Ig products