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Penyakit Autoimmune
Dr. E. Henny Herningtyas, MSi. PhD
Clinical Pathologi Department,
Faculty of Medicine, UGM Yogyakarta
Yogyakarta, 25 April 2012
4/25/2012 Kursus imunologi Dasar ke-11
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Mackay IR, 2000, BMJ 321: 93-96
Central tolerance: role of AIREThymus
Negative
selection
AIRE (+) AIRE (-)
= self Ag-expressed
thymus medullary cell = self-reactive- T cell
= non-reactive T-cell= apoptotic T-cell
AIRE = autoimmune regulator, turn on many peripheral gene on thymus
= non-self Ag-expressed
thymus medullary cell
Peripheral Tolerance
Regulatory tolerance by T regulatory
Thymus Cytokine release
T regulatory
Periphery
Naïve T cell
Autoreactive T cell
Autoreactive T cell
Clonal deletion B-cell in germinal center
Naïve B cell
B cell clones
self antigen
Autoimmune diseases and mechanism
Requirement for autoimmunity
Genetic factors
Infection and environmental
exposure
Breaking tolerance
Autoimmunity
HLA typing and risk of disease
Faktor genetik DM tipe 1
HLA DR3/4 increase susceptibility of
disease in type 1 DM
Shared HLA in sibling
increase susceptibility of
disease in type 1 DM
Autoimmunity is more
common in female
Single gene and autoimmunity
Infection induced autoimmunity
Breaking of antigen segregation
Sympathetic
opthalmia
Mechanism of autoimmune
Cluster of
autoimmune
diseases
Rheumatoid arthritis: 1% of general population, but female excess
SLE: 0.12% of general population, but female excess
Myasthenia gravis: 0.0% of general population, but female excess
Multiple sclerosis: 0.1% of general population but female excess
Primary Sjogren Syndrome: 0.6-3% of adult women
Thyroid disease: >3% of adult women
Type 1 diabetes: 0.1% of children
Prevalence of autoimmune diseases
Mackay IR, 2000, BMJ 321: 93-96
RA prevalence globally
Country Total
C.Spain 1.6%
Minnesota 1.07%
UK 0.81%
N.Spain 0.7%
Sweden 0.51%
France 0.5%
Tudela Spain 0.37%
N.Greece 0.35%
Country Total
Cordoba 0.34%
Oslo 0.33%
Greece 0.32%
N. Italy 0.32%
France 0.3%
Indonesia 0.25%
Yugoslavia 0.19%
Nigeria 0%
Prevalence in developing country is much lower than develop country
Darmawan, 1993, British Journal of Rheumatology, 32: 537-540
Systemic Lupus Erythematosus (SLE)
Autoantibody-mediated inflamation can lead to release of autoantigens from
damaged tissue and promotes further activation o f autoreactive B cells
Chronic stage
Systemic Lupus Erythematosus (SLE)Epitope spreading: B cells specific for various component of a complex
antigen are stimulated by a single specific autoreactive T cell
Rheumatoid Arthritis (RA)
Myasthenia gravis
Autoimmune Haemolytic Anemia (AIHA)
AIHA cases in YogyakartaAIHA cases in Yogyakarta
0
2
4
6
8
10
12
14
1997 1998 1999 2000 2001 2002
Year
Ca
se
nu
mb
er
Warm type
Cold type
Mix type
64.47%
35.53%
Perempuan
Laki-laki
Mean age of AIHA cases in Yogyakarta
0
10
20
30
40
50
1997 1998 1999 2000 2001 2002
Year
Pati
en
t ag
e
Mean
Male : female ratio = 1: 1.8
Herningtyas EH, 2003, Research reports (unpublished data)
Take home message:
Autoimmunity is a breaking of self-tolerance condition, influenced by genetic factor and environmental factor
Various mechanisms on autoimmune disease involving immune system at the level of T cell, B-cell and autoAbformation
Autoimmune disease prevalence vary in different type of disease and different countries
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