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 .
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 TATAU KEDUA2NYA
ATAU KEDUA2NYA .
ANTIGEN → AUTO ANTIGEN .
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 .
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 ) .
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 .
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 .
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
22AN > 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 .
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)
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
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 .
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 ..
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 .
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 :
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
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 .
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
( ) 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 )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) ,
zz
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 zSLE ( 35
SLE ( 35 40% )
40% )
z zSLE ( 35
SLE ( 35 –– 40% )
40% )
z zMCTD .
MCTD .
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
Cardioplipin Antibodis IgA,IgG,IgM
Cardioplipin Antibodis IgA,IgG,IgM
Cardioplipin Antibodis IgA,IgG,IgM
Cardioplipin Antibodis IgA,IgG,IgM
z
z
SLE .
SLE .
zz
Arterial & venous
Arterial & venous
zz
Arterial & venous
Arterial & venous
trombosis .
trombosis .
z zTrombositopenia
Trombositopenia
z zTrombositopenia .
Trombositopenia .
zThyroid Antibodi tests
Thyroid Antibodi tests
z
z
Thyroglobuli Antibodi Thyroid
Thyroglobuli Antibodi Thyroid
zz
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 .
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