IVIG IN MIS-C ,

IVIG as first line therapy in MIS-C

1. Dr. Vinaykumar S Appannavar MD
•MBBS at ShimogaInstitute of Medical Sciences, Shimoga
•MD at Vijayanagar institute of Medical Science, Ballari
•Currently working as Senior Resident in the Department of Pediatrics,
VIMS, Ballari
Area of Interests : PediatricIntensive care, Child Nutrition and Lactation management

2. IVIG IN MIS-C
Dr. Vinaykumar S Appannavar, MD
Senior Resident,
Department of Pediatrics,
VIMS -Ballari

3. BACKGROUND
▪MIS-Cisdefinedasacuteonsetoffeverthatmaybevariablyassociatedwithrash,
conjunctivalinjection,mucocutaneouserythema,coagulopathy,cardiovascular
complications,includingshockandcoronaryarterydilation,andgastrointestinalsymptoms,
includingabdominalpain,diarrhea,andvomiting.
and
▪Elevatedmarkersofinflammation–ESR,CRPandprocalcitonin
and
▪Nootherobviousmicrobialcauseofinflammation
and
▪EvidenceofCOVID-19orlikelycontactwithpatientswithCOVID-19
*AIIMS , New Delhi , Covid 19 in children guidelines

4. BACKGROUND
▪MIS-CdiffersfromKawasakiDiseaseinthatitismorecommoninolderchildren,and
gastrointestinalsymptomsarefrequentlyreported.
▪GiventhesimilarityofMIS-CwithKawasakidiseaseandthemacrophageactivation
syndromecomplicatingmanyrheumaticdisorders,intravenousimmunoglobulin(IVIG)and
steroidsformedthesheetanchorforMIS-Cmanagement2
▪Nearly2/3
rd
ofpatientsneedIntensivecaretreatment3
▪Mortalityis1.9%3
▪NeutrophilsinMIS-ChasHighexpressionofIL-1B(beta)4
▪IncreasedexpressionofCD32andCD16wasmoreonMIS-CneutrophilsComparedtoKD4
2 Indian Journal of Pediatrics, Narendra Kumar Bagri and M. Khan Et.al
3 Spotlight Unraveling the mechanisms of IVIG immunotherapy in MIS-C –GanigaraEt.al
4 Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C –Zhu Et.al

5. IVIG -Introduction
▪Donorpool–Derivedfrom2,000–10,000
donors,upto60,000donors
▪Composition–MonomericIgGupto>95%
withsmallamountsofIgMandIgApresent
▪Antibodycontent–01gmofIVIGcontains
4*1018moleculesofantibody
▪Stabilizedwithsugarsoraminoacids
Precipitation , agglutination and
neutralization of antigens
Activation of phagocytosis,
Complement mediated cytolysis,
NK cell –mediated cytolysis
-Neutralization of autoantibodies
-Downregulation of B and T cell function
-Cytokine regulation
-Fc receptor blockage
-Neutralization
of superantigens
-Elimination of
complement
activating
circulating
immune
complexes
Anti –infective MOA
Immunomodulatory
MOA
The Role of
IVIGs

6. Management
IVIGissuperiorinMIS-C
▪NeutrophilicactivationisthebasicmechanisminMISC5
▪NeutrophilsinMIS-ChasHighexpressionofIL-1B(beta)3
▪IVIGReducesmorethan50%ofneutrophilsandmorethan90%ofIL-1B
expressingneutrophilsinMIS-C3
3 Spotlight Unraveling the mechanisms of IVIG immunotherapy in MIS-C –GanigaraEt.al
5 Lee, M.S. Et.al Front Pediatr. 9, 640118.

7. Enhancestherecoveryrate
▪IVIGtargetsIL-1b+neutrophilstoamelioratetheinflammationinthis
inflammatorycondition6
▪IVIGanditsF(ab’)2fragmentsexertcytotoxiceffectsonneutrophils7
6 Henderson, Et.al American College of Rheumatology clinical guidance for multisystem inflammatory
7. Galeotti, C., Kaveri, S.V., and Bayry, J. (2017). IVIG-mediated effector functions in autoimmune and
inflammatory diseases. Int. Immunol.
Management

8. MOA
▪IVIGhasbeenshowntoinduceautophagyinhe
peripheralbloodmononuclearcellsbyF(ab’)2-and
PI3K-dependentpathways7
▪IVIGhasbeenshowntosuppresstheactivationof
Tcells,monocytes,dendriticcells,andendothelial
cellsthatareactivatedinMIS-C7
IVIG targets IL-1b+ neutrophils to exert anti-inflammatory
effects in MIS-C and Kawasaki disease (KD)
7. Galeotti, C., Kaveri, S.V., and Bayry, J. (2017). IVIG-mediated effector functions
in autoimmune and inflammatory diseases. Int. Immunol.

9. Merits -IVIG
1.ThereisevidencetoshowthatfasterinitiationofIVIGinchildrenwithMIS-Cwas
associatedwithreductioninlengthofPICUandhospitalstay8
2.Caseswithmilddisease,treatmentwithIVIG(2g/kgover12–24h,maximumdose
100g)
3.Mortality-7%3
4.Dosescanberepeated-Inchildrenhavingriskoffluidoverload,thedurationofIVIG
infusioncanbeincreasedto24–48h9
3 Spotlight Unraveling the mechanisms of IVIG immunotherapy in MIS-C –GanigaraEt.al
8 JonatB et.al Pediatr Crit Care Med 2021;22:e178–e191
9 Williams Va Et.al systematic review an meta-analysis. J PediatrIntensive Care 2020. doi:10.1055/s-0040-1719173.

10. Merits -IVIG
-Inthemanagementofimmunocompromisedstate
-Infungalinfections
-Ideal for use in MIS-C with co-morbidities
-Can be used in Kawasaki-disease like mimics

11. Take home message
IVIG Remains the drug
of choice in MIS-C
Enhances the
recovery rate
Reduces the length of
ICU and hospital stay
Ideal for use in MIS-C
with co-morbidities

12. References
•AIIMS , New Delhi , Covid 19 in children guidelines
•Indian Journal of Pediatrics, Narendra Kumar Bagri and M. Khan Et.al
•Spotlight Unraveling the mechanisms of IVIG immunotherapy in MIS-C –GanigaraEt.al
•Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C –Zhu Et.al
•Lee, M.S. Et.al Front Pediatr. 9, 640118.
•Henderson, Et.al American College of Rheumatology clinical guidance for multisystem inflammatory syndrome in children
•Galeotti, C., Kaveri, S.V., and Bayry, J. (2017). IVIG-mediated effector functions in autoimmune and inflammatory diseases.
•JonatB et.al Pediatr Crit Care Med 2021;22:e178–e191
•Williams Va Et.al systematic review an meta-analysis. J PediatrIntensive Care 2020. doi:10.1055/s-0040-1719173.

13. “
The person who takes medicine must
recover twice,
Once from the disease and once from
the medicine.
-Sir William Osler