Curriculum Vitae

Natsir Akil
Riwayat Pendidikan
• 1992 Dokter Umum UNHAS Makassar
• 2002 Internist UNHAS Makassar
• 2010 Konsultan Reumatologi FKUI/RSCM Jakarta
Riwayat Pekerjaan
• 1992-1995 : Kepala Puskesmas Sumarorong Kabupaten Polmas
Sulawesi Selatan
• 1996 : Staf RSUD Ampana Kabupaten Poso Sulawesi
tengah
• 2002–2009 : Staf RSUD Dr.H.Soemarno Sostroatmojo Tanjung
Selor Kabupaten Bulungan Kaltim
• 2010-sekarang : Staf SMF Penyakit Dalam RSU Kanujoso
Djatiwibowo Balikpapan Kaltim
Organisasi : IDI, PAPDI, IRA, PESLI, APLAR
 Clinical manifestation
of autoimmune disease

Natsir Akil
RS Kanujoso Djatiwibowo Balikpapan
Fakta tentang Penyakit Autoimmune (AI)
 Etiologi belum diketahui dengan pasti
 Banyak menyerang wanita muda.
 Gambaran klinik beberapa penyakit AI juga mirip penyakit
Non AI, terutama pada fase dini.
 Antara satu penyakit AI dengan yg lain juga kadang2
sulit membedakan.
 Angka kematian cukup tinggi.
 Pengobatan belum memberi hasil yg memuaskan
 Efek samping pengobatan
 The immune system
• The immune system is a network of organs, cells and molecules
that work together to defend the body against attacks by foreign
(not of the body) invaders such as germs, bacteria, viruses,
parasites and fungi.
 The immune system

Innate (non-specific) immunity Adaptive (specific) immunity

•Anatomic barriers (Skin,mucous •Antigen specificity

membranes)
•Diversity
•Physological barriers (temperature,
pH) •Immunological memory

•Phagocytic Barriers (cells that eat •Self/nonself recognition

invaders)
•Inflammatory barriers (redness,
swelling, heat and pain)
 Autotolerance
 Unresponsiveness to self antigens is known
as autotolerance
 Both B-cells and T-cells participate in
tolerence but T-cells play the primary role

Yamamoto K. JMAJ 2004; 47(9): 403–406.

Central Tolerance
Clonal–deletion:

* The process by which T-cells acquire the ability to

distinguish self from non self, in fetal thymus

* This involves the killing of T-cells that react against

antigens present in the fetus at that time
Elimination of
autoreactive B
cells in
germinal
centers
 Clinical Importance of Tolerance
1) Organ transplantation:
Introduction of tolerance may help in prevention of
rejection
2) Tumor development:
Tolerance to tumor antigen results in growth of the tumor
without being detected by the immune mechanisms
3) Autoimmune disorders:
Disturbance of self-tolerance results in autoimmune
disease
Organ specific Hashimoto Thyroiditis The Spectrum of
Primary myxedema
Thyrotoxicosis
Pernicious Anemia
Autoimmune
Autoimmune atrophic gastritis
Addison’s disease disease
Premature menopause (certain cases)
Male infertility (certain cases)
Myasthenia gravis
IDDM
Goodpasture’s syndrome
Pemphigus vulgaris
Pemphigoid
Sympathetic ophtalmia
Phacogenic uveitis
(Multiple sclerosis)
AIHA
ITP
Idiopathic leucopenia
Primary billiaris cirhosis
Active chronic hepatitis HBs-ve
Ulcerative colitis
Sjogren syndrome
Rheumatoid arthritis
Scleroderma
Wegener’s granulomatpsis
Poly/dermatomyositis
Non-organ Discoid lupus erythematosus Kelly et al, Text book of
specific Systemic lupus erythematosus (SLE) Rheumatology, 2005
Pathogenesis

Dysregulated cell death and dead cell clereance

Liu Y, Anders HJ. Nephron Clin Pract 2014;128:224–231

Lech M, Anders HJ. J Am Soc Nephrol 2013; 24:1357-66
Auto-vaccination with auto antigens

Liu Y, Anders HJ. Nephron Clin Pract 2014;128:224–231

Lech M, Anders HJ. J Am Soc Nephrol 2013; 24:1357-66
Pathogenesis
In situ immune complex formation and
glomerulonephritis

Liu Y, Anders HJ. Nephron Clin Pract 2014;128:224–231

Type-III Hypersensitivity: Immune Complex

Animation: Large quantities of soluble antigen-antibody complexes form in the blood

and are not completely removed by macrophages. These antigen-antibody complexes
lodge in the capillaries between the endothelial cells and the basement membrane. The
antigen-antibody complexes activate the classical complement pathway and complement
proteins and antigen-antibody complexes attract leukocytes to the area. The leukocytes
then discharge their killing agents and promote massive inflammation. This leads to
tissue death and hemorrhage
Type-II Hypersensitivity: ADCC

Host cell
Type-II Hypersensitivity: ADCC

Host cell
PREDICTIVE AUTOANTIBODIES
DISEASE AUTOANTIBODIES
Type 1 DM Anti-GAD, IA-2, IAA
Rheumatoid arthritis RF (anti IgG), ACPAs/Anti CCP Ab
Systemic Lupus Erythematosus Anti-PL, Anti-Ro, Anti-La, Anti-Sm, Anti-nuclear,
Ribonucleoprotein, Anti-dsDNA, Anti-Histone, Anti HS,
Anti nucleosome, Anti Ribosomal p protein
SjÖgren disease Anti-Ro, Anti-La
Anti phospholipid syndrome Lupus anti-coagulant, Anti cardiolipin
Primary Biliary Cirrhosis Anti-gp120, Anti-PDC
Autoimmune hepatitis ANA
Crohn’s disease ASCA
Ulcerative colitis pANCA
Autoimmune Addison’s disease ACA (adrenal cortec Ab / anti 21 hydroxylase)
Autoimmune Thyroid disease Anti-TG, Anti-TPO
Pemphigus Anti-desmoglein-1

Harel M, Shoenfeld Y. Ann NY Sci Acad. 2006;1069:322-45; Bizzaro N. Autoimmun Rev. 2007; 6:325–33;
BizzaroN,TozzoliR,ShoenfeldY. Arthritis Rheum. 2007; 56:1736–44.; ScofieldRH..Lancet.2004;363:1544–6.
Autoimmune disease symptoms
 Fatigue
 Achy muscles
 Swelling and redness
 Low-grade fever
 Trouble concentrating
 Numbness and tingling in the hands and feet
 Hair loss
 Skin rashes
 Alergi
 Anxiety & depression
 Sleep Disturbances
 Memory Problems
• Rheumatoid arthritis
Wanita : laki2 3 : 1
Artritis pada sendi2 kecil
kaku sendi pagi hari lebih dari 1 jam
Deformitas (swan neck, boutonniere dll)
RF positif
Anticcp positif
• SLE (Lupus)
Wanita : laki2 9 : 1
Demam subfebril
Sakit kepala
Artritis
Malar rash
Fotosensitifiti
Stomatitis
Kejang-kejang
Sesak napas
Sakit dada
Psikosis
Insomnia
Pucat
• Psoriatic arthritis
Oligoartritis pada tungkai bawah
Bercak kemerahan di badan (psoriasis)
Nyeri tulang belakang

• Angkilosing spondylitis
Inflamatory back pain
Sacroilitis
Bamboo spine
Angkilosis
• Antiphospholipid antibody syndrome
- Multiple miscarriages
- Positif pemeriksaan ACA (anti cardiolipin antibody) dan
LA (lupus anticoagulant).
 Systemic sclerosis (Scleroderma)
Penebalan dan pengerasan kulit
Raynaud’s phenomenon
Heart burn, GERD, kesulitan menelan
• Sjogren syndrome
Mata kering
Mulut kering
Pembesaran kelenjar dileher dan muka
Prinsip pengobatan penyakit AI
• Menekan aktifitas sistim imun
• Menggunakan steroid dan obat imunosupressan
• Mencari keseimbangan antara efikasi dari obat2an dan efek samping pengobatan
yang mungkin timbul
• Mengobati komorbiditas
• Tindakan non farmakologis
Obat-obatan imunosupressan

1. Steroid
2. Klorokuin/hidroksiklorokuin
3. Methotrexate (MTX)
4. Azathioprine (Imuran)
5. Siklosporin (Sandimun)
6. Cyclophosphamide
7. IV IG
8. Biologic agents
9. Cellcept/Myfortic
 Mycophenolic acid
1893 Discovered by an Italian medical scientist Bartolomeo Gosio

1912 two American scientists C.L. Alsberg and O.M. Black

resynthesised it in 1912, and gave its chemical name.

The clinically usable drug Cellcept was developed by South

African geneticist Anthony Allison and his wife Elsie M. Eugui

1995 first approved by the US Food and Drug Administration for use in
kidney transplantation.
The mechanism of action of mycophenolate
Both mycophenolate mofetil (MMF) and mycophenolate sodium (MMS) are almost completely
hydrolyzed to the active moiety mycophenolic acid (MMA) by esterases in the stomach, small
intestine, blood, liver, and tissues.

Antonio Perez-Aytes et al. Neoreviews 2010;11:e578-e589

 Mycophenolic acid (MMA)

• MMF should be considered as a first-line agent for induction, especially in young patients with
lupus. Bose B. Am J Kidney Dis. 2014;63(4):667-676

• Mycophenolate mofetil (MMF) is known to induce remission of LN in human.

Tang S at el. Nephrology 2005; 10 , 174–179

• MMF side effects including diarrhoea and abdominal discomfort.

• Enteric-coated mycophenolate sodium (EC-MPS) has less gastrointestinal adverse effects than
MMF.
• EC-MPS provides salutary efficacy and safety in the treatment of resistant-type PLN and can be a
suitably alternative treatment to ED-IVCY.
Traitanon O. Lupus (2008) 17,744–751

• MS was associated with improved efficacy in PSV and SLE compared with MMF.
Jones RB et al. Clin Kidney J (2014) 7:562–568
Kesimpulan
• Penyakit AI adalah kondisi dimana sistim imun tidak mengenali dirinya sendiri dan membentuk berbagai
macam sel dan autoantibodi yang menyerang berbagai macam organ.
• Etiologi belum diketahui dengan pasti.
• Ada dua yang sangat berperan didalam patogenesis penyakita AI yaitu sel B dan sel T.
• Proses kejadian AI, dimulai dengan terbentuknya autoantigen, yang kemudian dipresentasikan oleh sel APC
ke sel T, selanjutnya sel T mengaktifkan sel B, yang selanjutnya membentuk autoantibodi. Bertemunya
autoantigen dan autoantibodi merupakan awal dari terjadinya kerusakan orga.
• Pengobatan belum memberi hasil yang memuaskan, beberapa obat yang sering digunakan adalah steroid,
Imuran, sandimun, hydroxyclorokuin, siklofosfamid, cellcept, dan myfortic.
• Myfortic memiliki efektifitas disbanding cellcept dan efek samping yg minimal.
Terima kasih
• Autoimmune diseases are born when your body is working hard to
defend itself against something potentially dangerous, such as an
allergen, a toxin, an infection, or even a food, and it fails to
differentiate between the intruder and parts of your own body.
Mistaking certain types of tissues for harmful substances, your body
turns these antibodies against itself, wreaking havoc on your organs.