Clinical Application of Immunoglobulins in daily practice

1. Dr Sandhya Manorenj
September 20/2017
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2. Topic
 Definition
 Discovery
 Properties
 Preparations
 Mechanism
 Indications
 Dosage
 Adverse effects
 Conclusions
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Sandhya Manorenj

3. Immunoglobulins?
 Immunoglobulins are glycoprotein molecule which are
produced by plasma cell in response to an immunogen
and which function as antibodies.
. Clin Exp Immunol. 2009 Dec; 158(Suppl 1): 43–50
Sandhya Manorenj

4. Natural Antibodies?
 Natural antibodies are defined as those
immunoglobulins, preferentially of the IgM isotype,
which are produced by B lymphoyctes of the B1 type in
the absence of external antigen stimulation.
 Antibodies synthesized are in 2 forms :Soluble and cell
bound form.
 Soluble form is released into circulation as antibodies
and cell bound form is the BCR.
 Each B cell produce antibody of a single specificity and
express on their cell surface only 1 BCR specificity.
Clin Exp Immunol. 2009 Dec; 158(Suppl 1): 43–50
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Sandhya Manorenj

5. First usage of Immunoglobulin?
• Immunoglobulin products
in immunodeficiency
• Bruton et al1952
• IVIG initially shown
effective in ITP
• Imbach et al1981
Medscape June 2017
Sandhya Manorenj

6. Properties of immunoglobin
subtypes
Immunobiology 5th edition 2001.
Sandhya Manorenj

7. How do we get immunoglobin
for clinical usage?
 IVIG contains the
pooled immunoglobulin
G (IgG)
 Prepared from plasma of
approximately a 1000 or
more blood donors.
 Contains ≥ 95%
unmodified IgG and only
trace amounts of IgA or
IgM.
Medscape June 2017
Sandhya Manorenj

8. Steps in IVIG preparation
1000-10000 donars plasma pooled
Cohn Alcohol fractionation- 5 subfraction
of plasma
Further purification of cohn fraction II -
IVIG
Med J Armed Forces India. 2014 Jul; 70(3): 277–280.
Sandhya Manorenj

9. Indication of Immunoglobulins
 Used as a replacement
therapy
 As an
immunomodulatory
agent
 As an anti-inflammatory
agent.
Rev Bras Hematol Hemoter. 2011; 33(3): 221–230
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Sandhya Manorenj

10. Replacement therapy(IVIG)
Rev Bras Hematol Hemoter. 2011; 33(3): 221–230
Sandhya Manorenj

11. Immunomodulatory agent(IVIG)
Rev Bras Hematol Hemoter. 2011; 33(3): 221–230
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Sandhya Manorenj

12. Anti-inflammatory agent(IVIG)
. Rev Bras Hematol Hemoter. 2011; 33(3): 221–230
Sandhya Manorenj

13. TO summarize Mechanism of
IVIG
Clin Exp Immunol. 2005 Oct; 142(1): 1–11.
Sandhya Manorenj

14. Major indications of IVIG
Clin Exp Immunol. 2005 Oct; 142(1): 1–11.. 2005
Oct; 142(1): 1–11..
Sandhya Manorenj

15. Label indication of Ig use(FDA)
. Rev Bras Hematol Hemoter. 2011; 33(3): 221–230
Sandhya Manorenj

16. Intravenous immunoglobulin in
pediatrics
 a)Neurology – Guillain Barre syndrome, Chronic inflammatory
demyelinating polyradiculopathy (CIDP), Dermatomyositis and
inflammatory myopathies, Myasthenia gravis, rare childhood epilepsy
(Lennox gastaut seizure,Rasmussen encephalitis. Landau kleffner seizure),
Opsoclonus myoclonus ataxia, PANDAS (Paediatric autoimmune
neuropsychiatric disorders associated with streptococcal infection) – OCD,
anxiety, depression, emotional lability.
 b)Haematology – Idiopathic thrombocytopenic purpura, Pure red cell
aplasia, Pure white cell aplasia, Immune neutropenia, Immune haemolytic
anaemia.
 c)Immunology – Primary antibody deficiencies (XLA, CVID, HIGM, WAS
and others), Secondary antibody deficiencies.
 d)Dermatology – Kawasaki syndrome, Dermatomyositis, Toxic epidermal
necrolysis, Blistering diseases, Immune urticaria, Atopic dermatitis,
Pyoderma gangrenosum.
 e)Neonatology – Haemolytic disease of newborn due to Rh and ABO
incompatibility, Neonatal alloimmune thrombocytopenic purpura,
Bacterial sepsis in preterms.
 f)Others – Myocarditis, Systemic lupus erythematosus, Streptococcal toxic
shock syndrome, Autoimmune uveitis
Med J Armed Forces India. 2014 Jul; 70(3): 277–280.
Sandhya Manorenj

17. IVIG dose?
Low dose IVIG:200-600mg/kg
High dose IVIG: 2gm/kg
Conventional dose 400mg/kg/day
Med J Armed Forces India. 2014 Jul; 70(3): 277–280.
Sandhya Manorenj

18. What is the dosage of IVIG?
 ‘Replacement therapy ? “dose’ of 200–600 mg/kg body
weight, given approximately 3-weekly.(0.2—
0.6gm/kg/bw/day)
 Immunomodulatory’ agent? ‘high dose’ IVIG (hdIVIG),
given most frequently at 2 g/kg/month.
(0.4-1gm/kg/day )
 Conventional doses of intravenous immunoglobulin (i.v.Ig)
(0.4 g/kg/day for 5 days)
 ‘high’ dose IVIG is given at 2 g/kg (over 2–5 days for adults,
2 days for children)
Med J Armed Forces India. 2014 Jul; 70(3): 277–280,. . Rev Bras Hematol Hemoter. 2011; 33(3): 221–230Clin Exp Immunol. 2005 Oct; 142(1): 1–
11.2005 Oct; 142(1): 1–11.
Sandhya Manorenj

19. Adverse effects of IVIG
 1 Immediate infusion-
related
 Mild to moderate reactions
– headaches, backache,
chills, nausea, muscle pain
– occur in approximately
1% of infusions and are
largely rate-related.
 Severe – anaphylaxis may
occur very rarely in IVIG
recipients who have high
titres of anti-IgA
antibodies
 2Transmission of infective
agents
 Hepatitis C – several
outbreaks to date;
additional anti-viral step
introduced by most
manufacturers following
last outbreak in 1994
 ?Prions − potential risk;no
documented cases to date
Clin Exp Immunol. 2005 Oct; 142(1): 1–11..
Sandhya Manorenj

20. Adverse effects of IVIG-Conti-
 3 Consequences of
increasing serum IgG
 Renal – reversible renal
impairment (majority of
cases), acute renal failure
in mixed
cryoglobulinaemia.
 Haematological –
cerebral and coronary
thromboses, acute
haemolysis,,neutropenia.
 Neurological-acute
aseptic meningitis.
 Dermatological –
eczema, urticaria,
erythema multiforme
cutaneous vasculitis.
Clin Exp Immunol. 2005 Oct; 142(1): 1–11..
Sandhya manorenj

21. Infusion rate of IVIG
 Infusion rates are usually
started at 0.01–
0.02 ml/kg/min and
increased up to
0.1 ml/kg/min.
 5gm in 100ml available
Med J Armed Forces India. 2014 Jul; 70(3): 277–280.
Sandhya Manorenj

22. Conclusions
 Ig is the blood product with the fastest growing use in
the world.
 The immunomodulatory and anti-inflammatory
properties of this drug justify the many indications for
its use, with various levels of scientific evidence.
Med J Armed Forces India. 2014 Jul; 70(3): 277–280.
Sandhya Manorenj

23. MCQ ‘s
 1)IVIG’s peak effect occurs by
a) 2 weeks
b) 3 weeks
c)4 weeks
d) 3months
2)What is % of high dose IVIG transfusion AVR?
a)1-2%
b) 3-15%
c)5-10%
d) 8-15%
Med J Armed Forces India. 2014 Jul; 70(3): 277–280.
Sandhya Manorenj

24. MCQ’s
 3)What is the conventional dose of IVIG given for
immunomodulatory and antinflammatory action?
 a) 0.2gm/kg/d x 5 days
 b) 0.4gm/kg/d x 5 days
 c) 0.6 gm/kg/d x 5 days
 d) 1gm/kg/d x 5 days.
Med J Armed Forces India. 2014 Jul; 70(3): 277–280.
Sandhya Manorenj

25. MCQ ‘s
 4) The WHO has established the following production criteria
for IVIG ?
 a) It should contain at least 80% intact IgG with the subclasses
present in ratios similar to normal pooled plasma.
 b) It should contain at least 90% intact IgG with the subclasses
present in ratios similar to normal pooled plasma.
 c) It should contain at least 95% intact IgG with the subclasses
present in ratios similar to normal pooled plasma.
 d) It should contain at least 95% intact IgG with the subclasses
present in ratios not similar to normal pooled plasma
Med J Armed Forces India. 2014 Jul; 70(3): 277–280.
Sandhya Manorenj

26. Questions -
 5) What is the neurological complication of high dose
IVIG?
 6) Cardiac complication following high dose IVIG?
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Sandhya Manorenj

27. .
Sandhya Manorenj