1. THE ADVANTAGE OF SOY
FORMULA WITH LCPUFA
IN IMMUNITY AND
ALLERGY
Prof. Ariyanto Harsono MD PhD SpAK
1

2. Pendahuluan
Pencegahan alergi makanan:
 Primer
 Sekunder
 Tertier
Makanan Padat Menyesuaikan dengan formula Susu
yang digunakan
Suplemen yang Lain: LCPUFA, vitamin, mikronutrien
Soy Formula mempunyai efek positif dalam imunitas
dan Alergi 2

3. Immunol 2007:116:34-37
Environment
Antibiotics
3Prof DR Dr Ariyanto Harsono
SpA(K)

4. Aktivasi
sel-sel
Imuno-
kompeten
•Sel T
•Sel B
•Sel Mast
•Sel
Langer-
hans
Aktivasi
sel-sel
struk-
tural
•Sel
endotel
•Sel
epitel
Aktivasi dan
Rekruitmen
•Sel Mast
•Eosinofil
•Basofil
Pelepasan
mediator
Kerusakan
epitel
Stimulasi
neural
Dilatasi &
peningkatan
permeabilitas
vaskulerl
Bronkokonstriksi
Perbaikan
epitel
•Proliferasi
fibroblast
•Deposisi
kolagen
•Hipertropi/hiper
plasia otot polos
•Ekspansi
vaskuler
Penyempitan
saluran nafas
bawah
Symptom
alergi
Bronkus
hiper-reaktif
A
L
E
R
G
E
N
A B C D E
Imunopatologi alergi
Airway
remodelling
Primary Prevention Secondary Prevention
Tertiary PreventionJ Allergy Clin Immunol 2005;116:3-14
4

5. Ag
APC MHC-II Th0
IL-12/ IL-1
Th-2
Th.1
IL-1 IL-2, IFN-γ
B-Cell
IL-4
IL-5
SEL PLASMASEL MEMORI
IL-6
IL-10
AAKTIVASI SEL-SEL IMUNOKOMPETEN OLEH
ANTIGEN
Memory Cells
5

6. VACCINATION
ACTIVATION
ANTIGEN
SPECIFIC
B CELL
GENERATION OF
MEMORY
ACTIVATED
CD4
+
Th-2 CELL IL-4
DIFFERENTIATION
& AFFINITY
MATURATION
ANTIBODY SECRETING
PLASMA CELLS
ANTIGEN
PROCESSING &
PRESENTATION
MHC Class II B CELL IMMUNOGLOBULINE
T CELL RECEPTOR ANTIGEN
B CELL
IL-5,IL-13
Cow’s Milk Protein
Cow’s Milk epitope
6Prof DR Dr Ariyanto Harsono
SpA(K)

7. IgG
7Prof DR Dr Ariyanto Harsono
SpA(K)

8. IgA
TReg
TGF−β
8Prof DR Dr Ariyanto Harsono
SpA(K)

9. IgG
Th1 Cell
CTL
DTH
9Prof DR Dr Ariyanto Harsono
SpA(K)

10. B
AKTIVASI SEL-SEL STRUKTURAL
Nature Rev Immunol 2003; 3: 867-78
Eosinophil
Eosinophil
10Prof DR Dr Ariyanto Harsono
SpA(K)

11. C
PELEPASAN MEDIATOR
11Prof DR Dr Ariyanto Harsono
SpA(K)

12. D EFEK PELEPASAN MEDIATOR PADA TARGET ORGAN
Nature Rev Immunol 2004: 3:234-237
12Prof DR Dr Ariyanto Harsono
SpA(K)

13. Target
Organ
IgE-mediated disorder Non IgE-mediated
disorder
Skin
Gastro-
intestinal
Respiratory
Tract
Multi-
system
Urticaria and angioedema
Atopic Dermatitis
Oral Allergy Syndrome
Gastrointestinal anaphylaxis
Allergic eosinophilic
gastroenteritis
Asthma; Allergic Rhinitis
Food-induced anaphylaxis
Food associated, exercise-
induced anaphylaxis
Atopic Drmatitis
Dermatitis Herpetiformis
Proctocolitis
Enterocolitis
Allergic eosinophilic-GE
Enteropathy syndrome
Celiac Disease
GI Haemorrhage
Heiner Syndrome
Clinical ManifestationE Symptoms
13

14. Kehamilan = “Th2-disease”
*Anti-oksidan
*Hindari asap rokok
*Probiotik trimester
Pencegahan Primer: Masa Kehamilan
14

15. 15Prof DR Dr Ariyanto Harsono
SpA(K)

16. Prevensi Primer dengan susu
Formula
FORMULA H.A.Partially hydrolyzed
formulas:
16
Prof DR Dr Ariyanto Harsono
SpA(K)

17. Tujuan Prevensi Primer
1. Menimbulkan Toleransi Oral
2. Menurunkan prevalensi alergi
17Prof DR Dr Ariyanto Harsono
SpA(K)

18. Formula HA dalam Pencegahan primer
Bagaimana seharusnya?
*Harus mengandung sejumlah kecil
protein SS
*Tujuan adalah menginduksi toleransi
imun, bukan eliminasi SS
*Harus mengandung kasein dan whey
supaya terjadi toleransi thd keduanya
*Probiotik: dapat menyebabkan supresi
deviasi imun
US Nutrition guidelines
18
Prof DR Dr Ariyanto Harsono SpA(K)

19. Induction of Oral Tolerance
T-cells regulation:
1. Intra Epithelial Lymphocytes: extrathymically derived,
have limited TCR repertoir, capable of recognizing
common microbiologic Ags, and demonstrate
predominantly cytolytic functions
2. Lamina Propria Lymphocytes: thymicaly derived,
contributes to limiting TCR/CD3-mediated signals in the
mucosa
.
19Prof DR Dr Ariyanto Harsono
SpA(K)

20. Other Milk supplement
• Vitamin A juga dikenal dengan nama retinol merupakan
vitamin yang berperan dalam indra penglihatan yang
baik, terutama di malam hari, dan sebagai salah satu
komponen penyusun pigmen di retina. Selain itu, vitamin
ini juga berperan penting dalam menjaga kesehatan
kulit dan imunitas tubuh.
• Apabila terjadi defisiensi vitamin A, penderita akan
mengalami rabun senja dan katarak, mudah mengalami
infeksi saluran pernafasan.
Prof DR Dr Ariyanto Harsono
SpA(K)
20

21. Other Milk supplement…
* Lipid-soluble vitamin E has a capacity of
defense against oxidant-induced
membrane injury. Studies have
consistently demonstrated beneficial
associations between dietary vitamin E
and ventilatory function, and few have
demonstrated beneficial association with
asthma and atopy.
J Allergy Clin Immunol 2005;115:1109-17.
21Prof DR Dr Ariyanto Harsono
SpA(K)

22.  Water-soluble vitamin C provides anti-oxidant
capacity primarily by scavenging oxygen free
radicals and suppressing macrophage secretion
of super oxide anions, therefore play a role in
preventing mucosal shedding caused by
mediators released from eosinophils and
oxydants.
 n-3 polyunsaturated fatty acid (Omega-3),
eicosapantaenoic acid, and docahexaenoic acid
might have contributed to the decrease in
asthma and atopic disease morbidity.
Micronutrents: Fe, Zn, Se
J Allergy Clin Immunol
2005;115:1109-17.
Eur Respir J 1997;10:6-12.
22Prof DR Dr Ariyanto Harsono
SpA(K)

23. Arachidonic Acid (ARA)
Phospholiphase A
Cyccloxygenase Lipoxygenase
Prostaglandine
TXA
Prostacyclin
Leukotriene A
Leukotriene B
Leukotriene C
Omega-3, DHA
ecosapantaenoic
acid
HETE,5-HETE, PAF
PGD2/E2
PGD3 LTC4
LTC523

24. Prevensi Sekunder
Formula Advanved Hydrolyzed
Formula Soy Isolate
24Prof DR Dr Ariyanto Harsono
SpA(K)

25. Phytoestrogen
Biological consequences of soy-rich diets
have been attributed to the presence of
soy isoflavones, which are members of the
phytoestrogen family.
Phytoestrogens are plant-derived,
estrogen-like compounds capable of
interacting with the estrogen receptors ER
and ERβ because their structure
resembles that of the endogenous
hormone 17β-estradiol.
J. Clin. Invest. 2006 116:16-19
25Prof DR Dr Ariyanto Harsono
SpA(K)

26. Adrenocortical effects of oral estrogens and soy isoflavones in female
monkeys.
Results of study suggest that long-term
estrogen treatment may contribute to an
androgen-deficient and hypercortisolemic
state in animal model.
J Clin Endocrinol Metab 2004; 89: 2319-25
26Prof DR Dr Ariyanto Harsono
SpA(K)

27. Phytoestrogen...
Four groups of phenolic compounds are classified
as phytoestrogens:
isoflavones,
stilbenes,
coumestans, and
lignans.
The main isoflavones, found mostly in soybeans,
are:
 genistein,
 daidzein, and
 glycitein.
J. Clin. Invest. 2006 116:16-1927Prof DR Dr Ariyanto Harsono
SpA(K)

28. Phytoestrogen...
Several epidemiological studies have
concluded that phytoestrogens confer:
cardioprotection by downregulating
cardiovascular disease risk markers,
consistent improvement in endothelial
function
antioxidant activity. J. Clin. Invest. 2006 116:16-19
28Prof DR Dr Ariyanto Harsono
SpA(K)

29. H2O
29Prof DR Dr Ariyanto Harsono
SpA(K)

30. Phytoestrogen...
Soy product consumption has been
associated with the following:
reduced serum cholesterol levels via
reductions in total and low-density
lipoprotein levels;
vasodilatory activity under certain
conditions
enhanced activity of certain antioxidant
enzymes to increase antioxidant activities.
J. Clin. Invest. 2006 116:16-19
30Prof DR Dr Ariyanto Harsono
SpA(K)

31. A high intake of Soy and Isoflavones may
be associated with a reduced prevalence
of allergic Rhinitis
J Allery Clin Immunol 2005;115:1176-83
31Prof DR Dr Ariyanto Harsono
SpA(K)

32. Tujuan Prevensi Sekunder
1. Menurunkan morbiditas
2. Meningkatkan kualitas hidup
32Prof DR Dr Ariyanto Harsono
SpA(K)

33. IMMUNOMODULATORY AND
IMMUNOSUPRESSIVE EFFECTS OF
PUFAs
PUFAs modulate :
1. Cytokine production
2. Lymphocyte proliferation
3. Surface molecule expression
4. Phagocytosis and apoptosis
5. Inhibit natural killer (NK)cell activity
33Prof DR Dr Ariyanto Harsono
SpA(K)

34.  N-3 PUFA are better than n-6 PUFA
 The ratio of n-3 to n-6 may be an
important factor in modulating
inflammation
 Increasing the ratio of n-3 to n-6 
antiinflammatory effect especially with
atopic disease
34Prof DR Dr Ariyanto Harsono
SpA(K)

35. 35Prof DR Dr Ariyanto Harsono
SpA(K)

36. 36

37. Fish oil consumption during first
year of life and allergy
Effect of fish oil consumption in a cohort of 2531 Norwegian infantEffect of fish oil consumption in a cohort of 2531 Norwegian infant
J Asthma 2003;40:343
37Prof DR Dr Ariyanto Harsono
SpA(K)

38. LC-PUFA and immune
response
ARA DHA
Prostaglandine E2
Push B cells to produce IgE
Th1 Response
pro-inflammatory
anti-inflammatory
Antagonizes ARA
Prostaglandine E2
38Prof DR Dr Ariyanto Harsono
SpA(K)
Prostacyclin

39. Kesimpulan
 Pencegahan Primer dengan formula hipo-alergenik
harus dimulai sejak trimester pertama kehidupan,
tidak menunggu terjadinya gejala alergi. Makanan
tambahan seharusnya juga hipo-alergenik
 Pencegahan Sekunder menggunakan formula
advance hydrolyzed atau formula Soy Isolate
 Suplemen nutrisi lain: omega-3, ecosapentaenoic
acid, DHA berperan dalam modulasi imun mediator
inflamasi
 Anti-oksidan: Vitamin A, C, E
Micronutrients: Fe, Zn, Se
39Prof DR Dr Ariyanto Harsono
SpA(K)

40. Summary
1. In term infants, there are few indications for their use in place of cow
milk-basedformula:
• (a) for infants with galactosemiaand hereditary lactase deficiency
(rare) and
• (b) in situationsin which a vegetarian diet is preferred.
2. For infants withdocumented cow milk protein allergy, extensively
hydrolyzedprotein formula should be considered, because 10%to
14% ofthese infants will also have a soy protein allergy.
3. Most previouslywell infants with acute gastroenteritis canbe
managed afterrehydration with continued use of human milkor
standard dilutionsof cow milk-based formulas. Isolated soyprotein-
based formulasmay be indicated when secondary lactose
intolerance occurs. 40Prof DR Dr Ariyanto Harsono
SpA(K)

41. 4. Isolated soy protein-based formula has no advantage over cowmilk
protein-based formula as a supplement for the breastfedinfant,
unless the infant has 1 of the indications noted previously.
5. Soy protein-based formulas are not recommendedfor preterm
infants.
6. The routine use of isolated soy protein-basedformula has noproven
value in the prevention or managementof infantile colicor fussiness.
7. Infants with documented cowmilk protein-induced enteropathyor
enterocolitis frequentlyare as sensitive to soy proteinand should not
be given isolatedsoy protein-based formula.They should be
provided formula derivedfrom hydrolyzed proteinor synthetic amino
acids.
41Prof DR Dr Ariyanto Harsono
SpA(K)

42. 8. The routineuse of isolated soy protein-
based formula has noproven valuein the
prevention of atopic disease in healthyor
high-riskinfants.
42Prof DR Dr Ariyanto Harsono
SpA(K)

43. Thank You
43