PENGERTIAN DASAR : AUTOIMMUNITAS : ADALAH RESPONS IMUN TERHADAP ANTIGEN JARINGAN SENDIRI YANG

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SEROLOGI & IMMUNOLOGY

SEROLOGI & IMMUNOLOGY

DIAGNOSTIK PENYAKIT

DIAGNOSTIK PENYAKIT

AUTOIMMUNE

AUTOIMMUNE

AUTOIMMUNE

AUTOIMMUNE

PROF. ADI KOESOEMA AMAN SpPK(KH)

PROF. ADI KOESOEMA AMAN SpPK(KH)

p

p

(

(

)

)

PROF. RATNA AKBARI GANIE SpPK(KH) .

PROF. RATNA AKBARI GANIE SpPK(KH) .

DEPARTEMENT PATOLOGI KLINIK FK USU / RSUP DEPARTEMENT PATOLOGI KLINIK FK USU / RSUP

H. ADAM MALIK MEDAN . H. ADAM MALIK MEDAN .

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PENYAKIT AUTOIMMUN

PENYAKIT AUTOIMMUN

PENGERTIAN DASAR :

AUTOIMMUNITAS : ADALAH RESPONS IMUN TERHADAP ANTIGEN JARINGAN SENDIRI YANG

DI SEBABKAN OLEH HILANGNYA TOLERANSI →

DI SEBABKAN OLEH HILANGNYA TOLERANSI →

SECARA NORMAL TDK DAPAT MEMPERTAHAN

KAN “

SELF-TOLERANCE

” SEL B ATAU SEL T

ATAU KEDUA2NYA

ATAU KEDUA2NYA .

ANTIGEN → AUTO ANTIGEN .

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PENYAKIT AUTOIMMUN MELALUI

KOMPLEKS IMMUN

KOMPLEKS IMMUN .

1 Lupus Eritromatosus Sistemik ( LES )

1. Lupus Eritromatosus Sistemik ( LES ) .

2. Arteritis Reumatoid .

3 Sicca Komplex

3. Sicca Komplex .

4. Sindrom Goodpasteur .

5 Anemi Pernisiosa

5. Anemi Pernisiosa .

(15)

6. Reumatik Fever .

6. Reumatik Fever .

7. Sindrom Paska Perikariotomi .

7. Sindrom Paska Perikariotomi .

8

Sindrom Paska MCI ( Penyakit

8

Sindrom Paska MCI ( Penyakit

8. Sindrom Paska MCI ( Penyakit

8. Sindrom Paska MCI ( Penyakit

Dressler ) .

Dressler ) .

9. Skleroderma .

9. Skleroderma .

10. ITP .

10. ITP .

10. ITP .

10. ITP .

11. Penyakit Bulosa ( Vesikuler ) .

11. Penyakit Bulosa ( Vesikuler ) .

(16)
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Patogenesis terjadinya autoimmune

:

1. Antibodi dan autoimmunitas sendiri

menimbulkan kerusakan pada jaringan

menimbulkan kerusakan pada jaringan .

2 Penyakit

kerusakan jaringan

2. Penyakit

kerusakan jaringan

(neo-antigen)

respons immun .

3. Faktor lain

kerusakan jaringan

autoimmunitas

autoimmunitas .

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FAKTOR 2 RESIKO PENYAKIT

FAKTOR 2 RESIKO PENYAKIT

FAKTOR 2 RESIKO PENYAKIT

FAKTOR 2 RESIKO PENYAKIT

AUTOIMMUN.

AUTOIMMUN.

1. GENETIK

1. GENETIK

HUBUNGANNYA

HUBUNGANNYA

DENGAN

DENGAN

DENGAN

DENGAN

HLA .

HLA .

2

2

KELAMIN

KELAMIN

WANITA >>

WANITA >>

2.

2.

KELAMIN

KELAMIN

WANITA >> .

WANITA >> .

3.

3.

INFEKSI

INFEKSI

BEBERAPA INFEKSI

BEBERAPA INFEKSI

UMUM

UMUM

UMUM .

UMUM .

3.1.

3.1. EBV .

EBV .

3 2

3 2 STREPTOCOCCUS

STREPTOCOCCUS

3.2.

3.2. STREPTOCOCCUS .

STREPTOCOCCUS .

3.3.

3.3. MALARIA .

MALARIA .

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4

4..

SIFAT

SIFAT ,, SERING

SERING ANTIGEN

ANTIGEN UTUH

UTUH ..

4

4..1

1.. HEAT

HEAT SHOCKPROTEIN

SHOCKPROTEIN ..

4

4..2

2.. AUTOANTIGEN

AUTOANTIGEN ENZIM

ENZIM ..

5.

5. OBAT

OBAT

22

AN > DIANTARANYA :

AN > DIANTARANYA :

PROCAINAMIDE , HIDRALAZIN

PROCAINAMIDE , HIDRALAZIN

MENGINDUKSI GEJALA SEPERTI

MENGINDUKSI GEJALA SEPERTI

SLE .

SLE .

6. USIA

6. USIA

LEBIH TINGGI PADA USIA

LEBIH TINGGI PADA USIA

LANJUT .

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PENYAKIT AUTOIMUN ORGAN SPESIFIK

.

No PENYAKIT . ANTIGEN .

1. Penyakit Addison. Protein Mikrosome sel Adrenal. 2. Penyakit autoimun hemolitik Membran sel darah merah

3 Anemia pernisiosa Antigen sel parietal gaster 3. Anemia pernisiosa Antigen sel parietal gaster

Faktor intrinsic

4. Sindrome Gullain-Barre Saraf perifer (gangliosides)p (g g ) 5. Ensefalomielitis diseminasi akut Basic Protein Myelin

6. IDDM Antigen sel Lamgerhans pancreas 7. Sindrom Goodpasture Kolagen membrane basalis (Tipe IV) 8. Penyakit Grave Thyroid Stimulating Hormone Receptor 9 Ti iditi H hi t Ti l b li

9. Tiroiditis Hashimoto Tiroglobulin

10. Miastenia gravis Reseptor asetilkolin

11. Sindrom Sjogren Sel epitel saluran kelenjar saliva 11. Sindrom Sjogren Sel epitel saluran kelenjar saliva 12. Polimiositis Otot (Histidine tRNA Synthetase)

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1.

1.

PENYAKIT AUTOIMMUN MELALUI

PENYAKIT AUTOIMMUN MELALUI

ANTIBODI .

ANTIBODI .

Anemi

Anemi Hemolitik

Hemolitik Autoimmun

Autoimmun (( AHA

AHA )) ..

11..11.. AHA

AHA Warm

Warm Antibodi

Antibodi ..

1.2. AHA Cold Antibodi

1.2. AHA Cold Antibodi

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3. PENYAKIT AUTOIMMUN MELALUI SEL T . 1. Skelrosis Multipel .

2 Enselomielitis Desiminasi Akut ( EMDA ) 2. Enselomielitis Desiminasi Akut ( EMDA ) . 3. Sindrom Gullien Barre ( Acut Idiopathic

Polyneuritis ) . 4. Goiter .

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4.

4. PENYAKIT AUTOIMMUN MELALUI FOKTOR PENYAKIT AUTOIMMUN MELALUI FOKTOR HUMORAL

HUMORAL HUMORAL . HUMORAL .

11.. DMDM TipeTipe II (( IDDMpepe (( IDDM ,, Juvenile,, Ju e eJuvenile DMJu e e DM )) ..))

22.. TiroiditisTiroiditis KronisKronis (( TiroiditisTiroiditis HashimotoHashimoto )) .. 33.. PolimiositisPolimiositis-- DermatimiositisDermatimiositis ..

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AUTOANTIBODI PADA PENYAKIT AUTOIMMUN .

No JENIS PENYAKIT . AUTOANTIBODI SPESIFIK

1. AIHA . Eritrosit .

2. ITP . Trombosit .

3. LES . Antigen Nuklier , Antigen Jaringan , Sel Darah .

4. Reumatoid Arteritis . IgG .

5. Bilieri Sirosis Primer Mitokondria .

6. Kolitis Ulseratip Lipopolisakarida Kolon .

7. Tiroiditis Hashimoto Tiroglobulin .

8. Tirotoksikosis. Reseptor TSH

9. Anemi Pernisiosa . Faktor Instrinsik .

10 Myestenia Gravis Reseptor Asetilkolin dan jaringan otot tertent

tertentu .

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BEBERAPA AUTOANTIBODI PD AUTOIMMUN BEBERAPA AUTOANTIBODI PD AUTOIMMUN

DISORDERS . DISORDERS .

1. Anti DNA .

1. Anti DNA .

1.1. ds

1.1. ds--DNA ( double stranded DNA )

DNA ( double stranded DNA )

(

(

)

)

1.2. ss

1.2. ss--DNA ( single stranded DNA )

DNA ( single stranded DNA )

2. Antinucleoprotein ( soluble

2. Antinucleoprotein ( soluble

p

p

(

(

nucleoprote

nucleoprote

in = sNP ) ; DNA Histone .

in = sNP ) ; DNA Histone .

) ;

) ;

3. Antibasic nuclear protein ( histone ) .

3. Antibasic nuclear protein ( histone ) .

4. Antiacidic nuclear protein (

4. Antiacidic nuclear protein (

p

p

(

(

extractable nuclear antigen ( ENAs )

extractable nuclear antigen ( ENAs )

termasuk :

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RNA

RNA Smith (Sm) dan Ribonucleoprotein Smith (Sm) dan Ribonucleoprotein ( RNP ) . ( RNP ) . a. Nuclear glycoprotein ( Sm ) . a. Nuclear glycoprotein ( Sm ) . b. Ribonucleoprotein ( RNP ) . b. Ribonucleoprotein ( RNP ) . Sj ’ d A d B ( Sj ’ d A d B ( AA

c. Sjogren’s syndrome A dan B (ss c. Sjogren’s syndrome A dan B (ss--AA

& ss

& ss--B)B)

5 Antinucleolar ( nuclear RNA ) 5 Antinucleolar ( nuclear RNA ) 5. Antinucleolar ( nuclear RNA ) . 5. Antinucleolar ( nuclear RNA ) . 6. Anticytoplasmic ( Ribosomal

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REAKSI SEL THD FLUORESCENT TEST REAKSI SEL THD FLUORESCENT TEST REAKSI SEL THD FLUORESCENT TEST REAKSI SEL THD FLUORESCENT TEST

METHODE DARI ANA . METHODE DARI ANA . 1. Rim ( periperal )

1. Rim ( periperal ) →→

Native ds

Native ds--DNA DNA →→ hub . dg. Penyakit : hub . dg. Penyakit :

1.1. SLE . 1.1. SLE . 1.1. SLE . 1.1. SLE . 1.2. RA ( Rheumatoid Arteritis ) . 1.2. RA ( Rheumatoid Arteritis ) .

1.3. PSS ( Progresive systemik sclerosis ) 1.3. PSS ( Progresive systemik sclerosis ) 1 4 SS ( S ogren’s s ndrome

1 4 SS ( S ogren’s s ndrome 1.4. SS ( Syogren’s syndrome , 1.4. SS ( Syogren’s syndrome ,

1.5. MCTD ( mixed connective tissue disease 1.5. MCTD ( mixed connective tissue disease ..

1 6 DM 1 6 DM 1.6. DM . 1.6. DM .

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2. Solid ( diffus , homogenous ) 2. Solid ( diffus , homogenous ) →→

ds DNA , Histone,DNP ( deoxyribonucleo ds DNA , Histone,DNP ( deoxyribonucleo

--t i (DNA

t i (DNA hi thi t l ) l ) iti iti protein (DNA

protein (DNA--histone complex) histone complex) →→ positip positip

pd : SLE , drug induce SLE , MCTD , PSS , pd : SLE , drug induce SLE , MCTD , PSS , RA

RA RA . RA .

3. Speckled

3. Speckled →→ ENA (extractable nuclear ENA (extractable nuclear

antigen ) antigen )

(Sm , RNP ) , SS

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( ) d

kit SLE PSS MCTD SS

( ) d

kit SLE PSS MCTD SS

(+) pd penyakit :SLE,PSS,MCTD,SS ,

(+) pd penyakit :SLE,PSS,MCTD,SS ,

RA .

RA .

4 Nucleolar

4 Nucleolar

Nucleolar

Nucleolar

positip pada

positip pada

4. Nucleolar

4. Nucleolar

Nucleolar

Nucleolar

positip pada

positip pada

penyakit : PSS ( skleroderma ) , SLE ,

penyakit : PSS ( skleroderma ) , SLE ,

RA .

RA .

5. Centromere .

5. Centromere .

centromere

centromere

positip

positip

pada penyakit : CREST syndrome

pada penyakit : CREST syndrome

( l i i R ld’ h h i l tilit ( l i i R ld’ h h i l tilit (calcinosis ,Raynold’s phenomenon ,esophagial motility (calcinosis ,Raynold’s phenomenon ,esophagial motility dysfunction,sclerodactyly telengiectasa

dysfunction,sclerodactyly telengiectasa

) ,PSS ,PBC

) ,PSS ,PBC

(primary billiary cirrhosis )

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Antibodis thd Extratable Nuclear Antigen (

Antibodis thd Extratable Nuclear Antigen (

ENA )

ENA )

ENA )

ENA )

z

z

RNP

RNP--antibodi , Amti

antibodi , Amti--smith (Sm) ,

smith (Sm) ,

z

z

RNP

RNP antibodi , Amti

antibodi , Amti smith (Sm) ,

smith (Sm) ,

Anti sjogren’s sindrome ,Anti

Anti sjogren’s sindrome ,Anti

skleroderma ( Scl

skleroderma ( Scl--70 ) Anti

70 ) Anti ––Jo

Jo--1 (

1 (

skleroderma ( Scl

skleroderma ( Scl 70 ) Anti

70 ) Anti Jo

Jo 1 (

1 (

Jo

Jo--1 ).

1 ).

z z

SLE ( 35

SLE ( 35 40% )

40% )

z z

SLE ( 35

SLE ( 35 –– 40% )

40% )

z z

MCTD .

MCTD .

(43)

ELISA screening for Spesific systemic Rheumatic

ELISA screening for Spesific systemic Rheumatic

di

( SRD )

di

( SRD )

disease ( SRD )

disease ( SRD )

Test Spesific SRD

Test Spesific SRD

1.Anti

1.Anti--RNP MCTD

RNP MCTD

1.Anti

1.Anti RNP MCTD

RNP MCTD

2.Anti

2.Anti--Sm SLE, MCTD,SS .

Sm SLE, MCTD,SS .

3 A ti

3 A ti SSA/SSB Sj

SSA/SSB Sj

d

d

3.Anti

3.Anti--SSA/SSB Sjogren’s syndr.

SSA/SSB Sjogren’s syndr.

4.Anti

4.Anti--Scl

Scl--70 Scleroderma .

70 Scleroderma .

Anti Jo

(44)

Cardioplipin Antibodis IgA,IgG,IgM

Cardioplipin Antibodis IgA,IgG,IgM

Cardioplipin Antibodis IgA,IgG,IgM

Cardioplipin Antibodis IgA,IgG,IgM

z

z

SLE .

SLE .

z

z

Arterial & venous

Arterial & venous

z

z

Arterial & venous

Arterial & venous

trombosis .

trombosis .

z z

Trombositopenia

Trombositopenia

z z

Trombositopenia .

Trombositopenia .

z

(45)

Thyroid Antibodi tests

Thyroid Antibodi tests

z

z

Thyroglobuli Antibodi Thyroid

Thyroglobuli Antibodi Thyroid

z

z

Thyroglobuli Antibodi ,Thyroid

Thyroglobuli Antibodi ,Thyroid

mikrosomal antibodi ,

mikrosomal antibodi ,

Thyroperoxidase antibodi .

Thyroperoxidase antibodi .

Thyroperoxidase antibodi .

Thyroperoxidase antibodi .

1. Hyperthyroid

1. Hyperthyroid –– Ab

Ab

( Hashimoto’s thyroiditis )

( Hashimoto’s thyroiditis )

( Hashimoto’s thyroiditis )

( Hashimoto’s thyroiditis )

2. Hypothyroid

2. Hypothyroid –– Ab

Ab

( h

th

id )

( h

th

id )

( hypothyroid ) .

( hypothyroid ) .

3. Thyroid Ca .

3. Thyroid Ca .

(46)

Autoimmune Liver Disease tetst.

Autoimmune Liver Disease tetst.

Autoimmune Liver Disease tetst.

Autoimmune Liver Disease tetst.

Disease Anti

Disease Anti--Smooth Anti ANASmooth Anti ANA Muscle (%) Mitochon % Muscle (%) Mitochon % drial ( % ) drial ( % ) drial ( % ) drial ( % ) 1.Chro.Activ.Hepatitis 70 1.Chro.Activ.Hepatitis 70 -- 90 30 90 30 –– 60 6060 60 2. Chro.Perst.Hepatitis 45 15 2. Chro.Perst.Hepatitis 45 15 –– 20 1520 15--3030 3 A t Vi l H titi 10 3 A t Vi l H titi 10 30 5 30 5 20 2020 20 3. Act.Viral Hepatitis 10 3. Act.Viral Hepatitis 10--30 5 30 5 –– 20 2020 20 4.Act.Alc.Hepatitis 0 0 0 4.Act.Alc.Hepatitis 0 0 0 5.Billiary Cirosis 30 60 5.Billiary Cirosis 30 60 -- 70 570 5 6.Cryptogenic Cirrho. 15 30 0 6.Cryptogenic Cirrho. 15 30 0 7.Alcoholic Cirrho. 0 0 0 7.Alcoholic Cirrho. 0 0 0

8.Extrahepatic Bill. Obst. 5 8.Extrahepatic Bill. Obst. 5 –– 10 5 10 5 –– 10 510 5

8.Extrahepatic Bill. Obst. 5 8.Extrahepatic Bill. Obst. 5 10 5 10 5 10 510 5

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