Autoimmunity and

Covid-19
Amin Soebandrio
Department of Clinical Microbiology FKUI
 Immune Response

https://babygest.com/en/antiphospholipid-syndrome/
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 Autoimmunity
• Defined as an immune
response leading to
reaction with self antigen.
• Self antigen: any molecule
that is a normal body
constituent of the antimal
mounting the response.
• Self reactivity:
• Triggering of receptor
directly by auto-Ag.
• Cross-reaction
between foreign and
self Ag.
https://labpedia.net/elementary-immunology/chapter-16-autoimmunity/

Peter J Delves. Encyclopedia of Immunology 2nd Ed. 1998,

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 Autoimmune
Diseases

• https://www.companionhealthnc.
com/beyond-covid-19-autoimmune-
disease-and-the-gut/

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 AUTOANTIBODIES
ARE AN EXCELLENT
BIOMARKER FOR
AUTOIMMUNITY

There are literally hundreds of

different autoantibody tests a
physician can order nowadays. The
most common autoantibody test is the
so-called ANA (for anti-nuclear
antibody), which is performed using a
technique called immunofluorescence.

• Prevalence of ANA in the general

population by age and gender (Guo YP et al
Curr Ther Res, 2014).

https://pathology.jhu.edu/autoimmune/definitions
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Role of SARS-CoV-2

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This Photo by Unknown Author is licensed under CC BY
 The SARS-CoV-2 as an
instrumental trigger of
autoimmunity

• Hyper-stimulation of the immune

system by the SARS-CoV-2
• Molecular mimicry between SARS-
CoV-2 and humans
• Neutrophils extracellular traps
(NET) and SARS-CoV-2 infection:
another link with autoimmune
responses
• Autoantibodies in COVID-19-
infected patients
• Autoimmune diseases in COVID-
19-infected patients

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A. Dotan et al. Autoimmunity Reviews 20 (2021) 102792 7
 Mechanisms of virally induced autoimmunity

Moody R et all. Int. J. Mol. Sci. 2021, 22, 8965. https://doi.org/10.3390/ijms22168965

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 COVID-19 and
NETosis
• .SARS-CoV-2 viral particles invade the alveoli in the lung
where they bind type 2 pneumocytes via angiotensin-
converting enzyme 2
• (ACE2), which is also present on the surface of many other
cell types. As a result of the infection, neutrophils
transmigrate into the alveoli, where NETosis is activated
leading to release of decondensed chromatin (and other
nuclear, possibly modified, components) and granular
contents to the extracellular space.
A. SARS-CoV-2 invading the alveoli.
B. SARS-CoV-2 binding to the angiotensin-converting enzyme
2 of the type 2 pneumocytes.
C. Neutrophil transmigrating to the alveoli.
D. Neutrophil extracellular traps activation and release
(NETosis).
E. Enhancement of platelet aggregation induced by NETosis.
F. Neutrophil cytokines and proteases degranulation.
G. Modification of self-proteins in the citrullination induced
by peptidylarginine deiminases.

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A. Dotan et al. Autoimmunity Reviews 20 (2021) 102792 9
The effect of SARS-CoV-2 on the lungs and
the gastrointestinal (GI) tract and
demonstrates the dynamic interplay
between the lungs and the GI tract in
response to SARS-CoV-2.

• Presence of the SARS-CoV-2

virus not only leads to GI
manifestations in some patients
but may also alter the body’s
immune response to COVID-19.
• N. Katz-Agranov and G.
Zandman-Goddard.
Autoimmunity Reviews 20
(2021) 102865

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 Microbiotal similarities between COVID-19 and lupus.

N. Katz-Agranov and G. Zandman-Goddard. Autoimmunity Reviews 20 (2021) 102865

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 Immunologic pathways
activated by severe
acute respiratory
syndrome coronavirus 2

SARS-CoV2: Severe acute respiratory

syndrome coronavirus 2; TLR: Toll-like
receptor; IL: Interleukin; NLRP3:
Nucleotide oligomerization domain-
like receptor family pyrin domain
(PYD)-containing 3; NF-kB: Nuclear
factor-kB; RIG-I: Retinoic-acid
inducible gene I; MDA5: Melanoma
differentiation-associated protein 5;
IFN-I: Type I interferon; pDC:
Plasmacytoid dendritic cell; MHC:
Major histocompatibility complex;
TCR: T cell receptor; Th: T helper;
NET: Neutrophil extracellular trap.

Talotta R, Robertson E. World J Clin Cases 2020 September 6; 8(17): 3621-3919

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 Autoantibodies and autoimmune diseases associated with COVID-
19

18/05/2022
A. Dotan et al. Autoimmunity Reviews 20 (2021) 102792 13
 Possible relationship between
SARS-CoV-2 proteins and
autoimmune target proteins

Vojdani A et al (2021) Reaction of Human Monoclonal Antibodies to SARS-CoV-2

Proteins With Tissue Antigens: Implications for Autoimmune Diseases.
Front. Immunol. 11:617089. doi: 10.3389/fimmu.2020.617089
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Different new-onset autoimmune phenomena following diverse COVID-
19 vaccines

Chen et al. Immunology. 2022;165:386–401.

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Schematic depiction of
mechanisms inducing vaccine-
induced immune thrombotic
thrombocytopenia following
COVID-19 vaccination.

• Chen et al. Immunology.

2022;165:386–401.

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Potential
mechanisms
inducing
autoimmunity
through vaccine
adjuvants

18/05/2022 Chen et al. Immunology. 2022;165:386–401. 17

 Autoimmune Hepatitis

• Autoimmune hepatitis (AIH) is

an inflamatory liver diseases
which develops as a result of
an inadequate immune
response directed against liver
tissue.
• Self Limited autoimmunity
• Sustained autoimmunity in
AIH
• Extrinsic: Infection,
Drugs/Drug metabolites,
Microbiomes
• Intrinsic: Dysregulation of
immune system.
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Herkel J et al. J.Hepatol 2020 Vol 73: 446-448.
Acute, severe hepatitis of unknown origin
WHO working case definition
Confirmed
• N/A at present

Probable
• A person presenting with an acute hepatitis (non hepA-E*) with serum
transaminase >500 IU/L (AST or ALT), who is 16 years and younger, since 1
October 2021
Epi-linked
• A person presenting with an acute hepatitis (non hepA-E*) of any age who is a
close contact of a probable case, since 1 October 2021.
https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON376
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 Summary

Autoimmune Diseases
Immune
Genes Environment
system
Dietary
There isn’t a components
Polygenic Pollutants Drugs (such
single Autoimmune Cellular Auto- Infections
autoimmune
(multifactori
al) diseases
genes are Immunity antibodes (usually viral)
(feeding
infants with
(chemicals
like
as strepto-
zotocin, a
Stress
gene found in cow’s milk
many polychlorinat form of
instead of ed chemo-
chromo- mother’s
somes biphenyls) therapy)
milk, gluten,
lack of
vitamin D,
increased
ingestion of
iodine)
https://pathology.jhu.edu/autoimmune/development
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 Thank you

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https://www.clinicaltrialsarena.com/comment/acute-hepatitis-outbreak-children/