CURRICULUM VITAEName : Prof. Dr. dr. Iris Rengganis, SpPD, K-AI

Education :

- GP : Faculty of Medicine, Universitas Indonesia, 1983

- Internist : Faculty of Medicine, Universitas Indonesia, 1994

- Consultant in Allergy-Immunology : Faculty of Medicine, Universitas Indonesia, 2000

- PhD : Bogor Agricultural Institute, 2009

- Professor : Faculty of Medicine, Universitas Indonesia, 2019

Working Experiences :

- Community Health Center/Puskesmas, South Jakarta, 1984-1988

- Dr. Cipto Mangunkusumo Hospital, Central Jakarta, as fellow/PPDS, 1989-1994

- Jakarta Hajj Hospital, East Jakarta, as Internist,1995-1997

- Dr. Cipto Mangunkusumo Hospital, Central Jakarta, as staff in Allergy-Immunology, 1998-now

Organization :

- Board Member of PB.IDI (Indonesian Doctors Association)

- Treasurer of PB.PAPDI (Indonesian Society of Internal Medicine)

- President of PP.PERALMUNI / ISAI (Indonesian Society of Allergy and Immunology)

- Board Member of APAAACI (Asia Pacific Association of Allergy, Asthma and Clinical Immunology)

CURRICULUM VITAE

How to follow up diagnosis on some Autoimmunity Disease

Iris RengganisPerhimpupnan Alergi Imunologi Indonesia

ABREVIATIONS

Disease Abrev.

SYSTEMIC AUTOIMMUNE DISEASES

Connective Tissue Diseases CTD

Systemic Lupus Erithematosus SLE

Drug Induced Lupus DIL

Rheumatoid Arthritis RA

Sjögen Syndrome SjS

Dermatomyositis DM

Polimyositis PM

Sistemic Sclerosis / Sclerodermia Scl / SS

Limited Sclerodermia CREST

Antiphospholipid Syndrome APS

Mixed Connective Tissue Disease MCTD

ORGAN SPECIFIC DISEASES

Autoimmune Hepatitis AIH

Primary Biliary Chirrosis PBC

Celiac Disease CD

Inflammatory Bowel Disease IBD

ABREVIATIONS

PRODUCT ABREV.

Anti-Nuclear Antibodies ANA

Anti- Neutrophil Cytoplasmic Antibodies ANCA

Anti-Endomysium Antibodies AEA

Autoantibodies RL/RK/RS Triple

Anti-Mithocondrial Antibodies AMA

Anti-Smooth Muscle Antibodies ASMA

Glomerular Basement Antibodies GBMA

Anti - Adrenal Antibodies AACA

Anti-Striated Muscle Antibodies AStMA

Anti-Islet Cells Antibodies AICA

Anti-Thyroid Antibodies ATA

Anti-Skin Antibodies ASA

Anti-Keratin Antibodies AKA

PATTERN ABREV.

Liver - Kidney Microsomal LKM

Anti-liver-cytosol type 1 LC1

Anti-Mithocondrial Antibodies AMA

Anti-Smooth Muscle Antibodies ASMA

Anti-Nuclear Antibodies ANA

Anti-Reticulin Antibodies ARA

Connective Tissue DiseasesDiagnosis (Systemicautoimmune diseases)

CTD Diagnosis

• Systemic autoimmune diseases, theautoimmune responses are directedagainst self-antigens present in manyorgans and tissues of the bodyresulting in widespread tissuedamage to the host

• Difficult to diagnose:

• Similar symptoms• Overlap symptoms between

different conditions• Mild and non specific symptoms

• Many possible autoantibodiesinvolved (look for a needle in ahaystack)

CTD diagnosisSET THE PROBABLE DISEASE ACCORDING TO

THE SYMPTHOMS

APS? RA? VASCULITIS? OTHERS?

HEp2 (IFA)aCL (ELISA) Β2-GP1 (ELISA)

ACPA (ELISA)ANCA (IFA)

MPO/ PR3 (ELISA)

DEPENDING ON THE RESULTS AND ACCORDING TO THE SYMPTHOMS, SET THE DIAGNOSTIC

If positive search for specificity (ELISA)

Systemic Lupus Erithematosus (SLE)

• Chronic disease of unknown etiology.

• Prevalence of 15 to 50 patients every• 100.000 people

• Affects predominantly women (10:1).

• Start at 20’s – 30’s.

• 80% of patients at diagnostic show skin or joint involvement (malar rash, photosensitivity, alopecia, arthritis)

• Clinical laboratory focus on finding• Anti-Nuclear Antibodies (ANA)

• Basic markers:

• nDNA (75% patients)

• Sm

Systemic Sclerosis(Scl / SSc)

• Scleroderma is a process that induces fibrosis on skin, blood vessels and several internal organs like gastro-intestinal systems, lung, kidney and hearth.

• The prevalence is low, around 14 patients every million people.

• The main changes appear at:• Vascular endothelium• Immune system• Connective tissue

• There are two forms: diffuse and limited

• Clinical laboratory focus on finding Anti-Nuclear Antibodies (ANA)

Sjögren´s Syndrome(SjS)• Lymphocyte infiltration of exocrine glands develops

SjS symptoms:

• Mouth and eye dryness

• Swallowing difficulties

• Raynaud´s phenomenon

• Fever

• Joint pain

• Prevalence of 0,5 - 1%, specially on women

• 30% of patients with RA shows also SjS symptoms

• Laboratory findings (Revised criteria for SjS, 2002)

• Secretion test for salivary and lachrymalglands

• Specific presence of relevant markers (SSA and SSB) – (Hep2). This finding should not be used in patients aged 60 and over due to a high prevalence of irrelevant positives

Polymyositis /Dermatomyositis (PM/DM)

• Symptoms:

• Skin Rash

• Muscle weakness

• Loose of muscle mass

• Pain

• Although clinical features are similar, theyhave different pathogenic basis (DM iscomplement mediated, whereas PM is mediated by T lymphocytes cytotoxicity)

• Clinical laboratory focus on findingAnti-Nuclear Antibodies (ANA)

Mixed Connectivetissue disease(MCTD)

• Overlapping syndrome with clinicalfindings similar to those seen in SLE,SSc

• and PM/DM:• Raynaud's phenomenon• Swelling of hands and fingers• Myositis or muscle weakness

• Affects specially women (80% ofpatients)

• The main laboratory finding is ANAtesting: the presence of high titer of anti-RNP antibodies (diagnosticcriteria)

RheumatoidArthritis (RA)

• High incidence and prevalence (1%Caucasian population)

• Symptoms:

• Joint pain

• Joint swelling

• Weight loose

• Fatigue...

• The most common laboratoryfindings for RA diagnosis areACPA (ELISA) and RF.

• Other autoantibodies are found in upto 90% of patients

Suspicion Rheumatoid Arthritis

ELISA ACPA

ACPA or RFnegative

RF CRP ESR

ACPA or RFpositive

ACPA or RFlow positive

0 score points

2 score points

3 score points

AbnormalNormal

0 score points

1 score points

Rheumatoid Arthritis (RA)

Anti PhospholipidSyndrome (APS)

• Complex clinical symptoms:

• Thrombosis - Necrosis• Spontaneous miscarriage at or beyond

10th week of gestation

• Neurological disorders• Often associated with other autoimmune

connective tissue disease

• (secondary syndromes), specially SLE and RA

• Laboratory findings (APS-2006 criteria):

• Anticardiolipin (ELISA), IgG and/or IgM, at high titter in (>40• GPL/MPL) two consecutive test delayed 12 weeks.

• Lupus anticoagulant in plasma, in two consecutive test delayed at least 12 weeks.

Vasculitis

• Heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels.

• The ANCA associated vasculitidesare diagnosed by laboratory ANCAtest:

• Wegener´s Granulomatosis• Microscopic Poliangiitis• Churg – Strauss Syndrome

• Laboratory findings for ANCA associated vasculitis diagnosis are MPO– PR3 – GBM (by ELISA or IFA

Organ Specific Autoimmune Diseases (OSAD)

Primary Biliary Cirrhosis(PBC)

• Chronic destruction of the small bile conducts which produces liver tissue damage (cirrhosis).

• Affects 1 each 3.000 population

• The main and more specific autoantibody for PBC is AMA (anti-• mithocondrial antibodies) – present in 90 – 95% patients

• From the differentsubtypes of AMA, only M2 is considered relevant, although other subtypes are also present in PBC (M4 –M8 – M9)

• The triple substrate can virtually detect all subtypes of AMA

• Autoimmune hepatitis is a chronic disease of unknown cause and is characterized by continuing hepatocellular inflammation and necrosis and has a tendency to progress to cirrhosis.

• Is responsible of 10 – 20% of chronic hepatitis cases

• There are three types of AIH in correlation of autoantibodies:

Autoimmune Hepatitis

Autoantibody Prevalence Type AIH Characteristics

ANA 50 – 80%

AIH type 1 Most common type of AIHASMA 80%

LKM1 95 - 100%

AIH type 2

Usually affecting child and adolescent. Clinical manifestations similar to viric hepatitis. Worst

prognosis.LC150% (usually associated

with LKM1)

SLA/LP

20% (in AIH)100% inside the subgroup AIH type 3

Only differentiated serologically from AIH Type I.In the future could be removed.

Detectable in triple substrate

Autoimmune gastritis& Pernicious anemia

• Autoimmune gastritis (AG) ( Type A gastritis) is a chronic inflammation of gastric mucosathat produce destruction of parietal cells and chief cells.

• These effects leads to Vitamin B12 malabsorption and therefore, PerniciousAnemia

• For diagnosis of autoimmune gastritis there are two relevant markers:

• APCA (Anti-Parietal cellsantibodies)(90% cases) – ATPase H+/K+

• Intrinsic factor (50 – 70%)• Disease highly associated to Helicobacter

pylori• infection.

Celiac Disease

• Autoimmune disease of the small intestine that occurs in predisposed people from all ages where the ingestion of gluten leads to damagein the small intestine.

• It affects between 1 in 2000 to 1 in105 people.

• The test for diagnosis of CeliacDisease are:• AEA (IIF)• tTg (ELISA)• Gliadin (ELISA)• Deamidated Gliadin (ELISA)

Celiac Disease

Suspicion CD

Testing IgAdeficiency

tTg IgA

tTg IgG G/DGP IgG

AEA IgAG/DGP IgA/G

Celiac disease veryunlikely

+

-

+

-+

Proceed to biopsy

-

Possible false positive tTg result? If strong suspicion do HLA DQ2/ DQ8

test

+

Inflammatory BowelDiasease (IBD)

• Inflammatory bowel disease (IBD) is a term mainly used to describe two conditions affecting the bowels:

• Chron´s disease (CrD)

• Ulcerative colitis (UC)

• Both diseases have similar symptoms and are difficult todifferentiate.

• Two serological markers have been found to have aclinical utility in diagnosing IBD:

• Anti-Saccharomyces cerevisiae antibodies• (ASCA): more common in CrD (60 – 70%)• Anti-neutrophil cytoplasmic antibodies (ANCA)

– usually not MPO/PR3: more common in UC(60 – 80%)

Thank You for Your Attention