SEROLOGI & IMMUNOLOGY SEROLOGI & IMMUNOLOGY DIAGNOSTIK PENYAKIT DIAGNOSTIK PENYAKIT

AUTOIMMUNEAUTOIMMUNEAUTOIMMUNEAUTOIMMUNE

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 AUTOIMMUNPENYAKIT AUTOIMMUNPENGERTIAN DASAR :AUTOIMMUNITAS : ADALAH RESPONS IMUNTERHADAP ANTIGEN JARINGAN SENDIRI YANGDI SEBABKAN OLEH HILANGNYA TOLERANSI →DI SEBABKAN OLEH HILANGNYA TOLERANSI →SECARA NORMAL TDK DAPAT MEMPERTAHANKAN “SELF-TOLERANCE” SEL B ATAU SEL TATAU KEDUA2NYAATAU KEDUA2NYA .

ANTIGEN → AUTO ANTIGEN .ANTIBODI → AUTO ANTIBODI

PENYAKIT AUTOIMMUN MELALUIKOMPLEKS IMMUNKOMPLEKS IMMUN .

1 Lupus Eritromatosus Sistemik ( LES )1. Lupus Eritromatosus Sistemik ( LES ) .2. Arteritis Reumatoid .3 Sicca Komplex3. Sicca Komplex . 4. Sindrom Goodpasteur .5 Anemi Pernisiosa5. Anemi Pernisiosa .

6. Reumatik Fever .6. Reumatik Fever .7. Sindrom Paska Perikariotomi .7. Sindrom Paska Perikariotomi .8 Sindrom Paska MCI ( Penyakit8 Sindrom Paska MCI ( Penyakit8. 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 jaringanmenimbulkan kerusakan pada jaringan .

2 Penyakit → kerusakan jaringan2. Penyakit → kerusakan jaringan (neo-antigen) → respons immun .

3. Faktor lain → kerusakan jaringan →autoimmunitasautoimmunitas .

FAKTOR 2 RESIKO PENYAKIT FAKTOR 2 RESIKO PENYAKIT FAKTOR 2 RESIKO PENYAKIT FAKTOR 2 RESIKO PENYAKIT AUTOIMMUN.AUTOIMMUN.

1. GENETIK 1. GENETIK →→ HUBUNGANNYA HUBUNGANNYA DENGANDENGANDENGAN DENGAN

HLA .HLA .22 KELAMINKELAMIN WANITA >>WANITA >>2.2. KELAMIN KELAMIN → → WANITA >> .WANITA >> .

3.3. INFEKSI INFEKSI → → BEBERAPA INFEKSI BEBERAPA INFEKSI UMUMUMUMUMUM .UMUM .

3.1.3.1. EBV .EBV .3 23 2 STREPTOCOCCUSSTREPTOCOCCUS3.2.3.2. STREPTOCOCCUS .STREPTOCOCCUS .

3.3.3.3. MALARIA .MALARIA .

44.. SIFATSIFAT ,, SERINGSERING ANTIGENANTIGEN UTUHUTUH ..44..11.. HEATHEAT SHOCKPROTEINSHOCKPROTEIN ..44..22.. AUTOANTIGENAUTOANTIGEN ENZIMENZIM ..

5. 5. OBAT OBAT 22AN > DIANTARANYA : AN > DIANTARANYA : PROCAINAMIDE , HIDRALAZIN PROCAINAMIDE , HIDRALAZIN →→MENGINDUKSI GEJALA SEPERTIMENGINDUKSI GEJALA SEPERTISLE .SLE .

6. USIA 6. USIA → → LEBIH TINGGI PADA USIA LEBIH TINGGI PADA USIA LANJUT .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 gaster3. 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 li9. Tiroiditis Hashimoto Tiroglobulin

10. Miastenia gravis Reseptor asetilkolin

11. Sindrom Sjogren Sel epitel saluran kelenjar saliva11. Sindrom Sjogren Sel epitel saluran kelenjar saliva

12. Polimiositis Otot (Histidine tRNA Synthetase)

1.1. PENYAKIT AUTOIMMUN MELALUIPENYAKIT AUTOIMMUN MELALUIANTIBODI .ANTIBODI .

AnemiAnemi HemolitikHemolitik AutoimmunAutoimmun (( AHAAHA )) ..

11..11.. AHAAHA WarmWarm AntibodiAntibodi ..

1.2. AHA Cold Antibodi 1.2. AHA Cold Antibodi

2. Myastenia Gravis .

Tirotoksikosis .

3. PENYAKIT AUTOIMMUN MELALUI SEL T .

1. Skelrosis Multipel .

2 Enselomielitis Desiminasi Akut ( EMDA )2. Enselomielitis Desiminasi Akut ( EMDA ) .

3. Sindrom Gullien Barre ( Acut IdiopathicPolyneuritis ) .

4. Goiter .4. Goiter .

4.4. PENYAKIT AUTOIMMUN MELALUI FOKTOR PENYAKIT AUTOIMMUN MELALUI FOKTOR HUMORAL HUMORAL HUMORAL .HUMORAL .

11.. DMDM TipeTipe II (( IDDMIDDM ,, JuvenileJuvenile DMDM )) ..pepe (( ,, Ju e eJu e e ))

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 , SelDarah .

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 otottertenttertentu .

11 DM Tipe I ( Juvenil ) Permukaan sel Langerhans Pankreas

BEBERAPA AUTOANTIBODI PD AUTOIMMUN BEBERAPA AUTOANTIBODI PD AUTOIMMUN DISORDERS .DISORDERS .

1. Anti DNA .1. Anti DNA .1.1. ds1.1. ds--DNA ( double stranded DNA )DNA ( double stranded DNA )( )( )1.2. ss1.2. ss--DNA ( single stranded DNA )DNA ( single stranded DNA )

2. Antinucleoprotein ( soluble 2. Antinucleoprotein ( soluble p (p (nucleoprotenucleoprotein = 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 :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 ( AAc. Sjogren’s syndrome A dan B (ssc. 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 ( Ribosomal6. 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 dsNative 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 (DNAt i (DNA hi t l ) hi t l ) iti iti protein (DNAprotein (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(Sm , RNP ) , SS--A ,SSA ,SS--B,Skleroderma 70B,Skleroderma 70..

( ) 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 Nucleolar4 Nucleolar →→ NucleolarNucleolar →→ positip padapositip pada4. 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 telengiectasadysfunction,sclerodactyly telengiectasa ) ,PSS ,PBC ) ,PSS ,PBC (primary billiary cirrhosis ) (primary billiary cirrhosis )

Antibodis thd Extratable Nuclear Antigen ( Antibodis thd Extratable Nuclear Antigen ( ENA )ENA )ENA )ENA )

RNPRNP--antibodi , Amtiantibodi , Amti--smith (Sm) , smith (Sm) , RNPRNP antibodi , Amtiantibodi , Amti smith (Sm) , smith (Sm) , Anti sjogren’s sindrome ,Anti Anti sjogren’s sindrome ,Anti skleroderma ( Sclskleroderma ( Scl--70 ) Anti 70 ) Anti ––JoJo--1 ( 1 ( skleroderma ( Sclskleroderma ( Scl 70 ) Anti 70 ) Anti JoJo 1 ( 1 ( JoJo--1 ).1 ).SLE ( 35 SLE ( 35 40% ) 40% ) SLE ( 35 SLE ( 35 –– 40% ) 40% ) MCTD .MCTD .

ELISA screening for Spesific systemic Rheumatic ELISA screening for Spesific systemic Rheumatic di ( SRD )di ( SRD )disease ( SRD )disease ( SRD )

Test Spesific SRDTest Spesific SRD1.Anti1.Anti--RNP MCTDRNP MCTD1.Anti1.Anti RNP MCTDRNP MCTD2.Anti2.Anti--Sm SLE, MCTD,SS .Sm SLE, MCTD,SS .3 A ti3 A ti SSA/SSB Sj ’ dSSA/SSB Sj ’ d3.Anti3.Anti--SSA/SSB Sjogren’s syndr.SSA/SSB Sjogren’s syndr.4.Anti4.Anti--SclScl--70 Scleroderma .70 Scleroderma .Anti JoAnti Jo--1 Polimyositis .1 Polimyositis .

Cardioplipin Antibodis IgA,IgG,IgMCardioplipin Antibodis IgA,IgG,IgMCardioplipin Antibodis IgA,IgG,IgMCardioplipin Antibodis IgA,IgG,IgM

SLE .SLE .Arterial & venous Arterial & venous Arterial & venous Arterial & venous trombosis .trombosis .Trombositopenia Trombositopenia Trombositopenia .Trombositopenia .Recurrent fetal loss .Recurrent fetal loss .

Thyroid Antibodi testsThyroid Antibodi tests

Thyroglobuli Antibodi Thyroid Thyroglobuli Antibodi Thyroid 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 –– AbAb

( 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 AntiDisease Anti--Smooth Anti ANASmooth Anti ANAMuscle (%) Mitochon %Muscle (%) Mitochon %

drial ( % )drial ( % )drial ( % )drial ( % )1.Chro.Activ.Hepatitis 70 1.Chro.Activ.Hepatitis 70 -- 90 30 90 30 –– 60 6060 602. Chro.Perst.Hepatitis 45 15 2. Chro.Perst.Hepatitis 45 15 –– 20 1520 15--30303 A t Vi l H titi 103 A t Vi l H titi 10 30 5 30 5 20 2020 203. Act.Viral Hepatitis 103. Act.Viral Hepatitis 10--30 5 30 5 –– 20 2020 204.Act.Alc.Hepatitis 0 0 04.Act.Alc.Hepatitis 0 0 05.Billiary Cirosis 30 60 5.Billiary Cirosis 30 60 -- 70 570 56.Cryptogenic Cirrho. 15 30 06.Cryptogenic Cirrho. 15 30 07.Alcoholic Cirrho. 0 0 07.Alcoholic Cirrho. 0 0 08.Extrahepatic Bill. Obst. 5 8.Extrahepatic Bill. Obst. 5 –– 10 5 10 5 –– 10 510 58.Extrahepatic Bill. Obst. 5 8.Extrahepatic Bill. Obst. 5 10 5 10 5 10 510 5