Penyakit Autoimmune

Dr. E. Henny Herningtyas, MSi. PhD

Clinical Pathologi Department,

Faculty of Medicine, UGM Yogyakarta

henny_herningtyas@yahoo.com

Yogyakarta, 25 April 2012

4/25/2012 Kursus imunologi Dasar ke-11

c

c

c

c

cc c

c

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

Terima kasih atas perhatian yang

anda berikan