THE ADVANTAGE OF SOY FORMULA WITH LCPUFA

IN IMMUNITY AND ALLERGY

Prof. Ariyanto Harsono MD PhD SpAK

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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

Immunol 2007:116:34-37

Environment

Antibiotics

3Prof DR Dr Ariyanto Harsono SpA(K)

Aktivasi sel-selImuno-kompeten•Sel T•Sel B•Sel Mast•Sel Langer- hans

Aktivasi sel-selstruk-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/hiperplasia otot polos•Ekspansi vaskuler

Penyempitan saluran nafas bawah

Symptom alergi

Bronkus hiper-reaktif

ALERGEN

A B C D E

Imunopatologi alergi

Airway remodelling

Primary Prevention Secondary Prevention

Tertiary PreventionJ Allergy Clin Immunol 2005;116:3-14

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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

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VACCINATION

ACTIVATIONANTIGEN SPECIFIC

B CELL

GENERATION OF MEMORY

ACTIVATED CD4

+ Th-2 CELL IL-4

DIFFERENTIATION

& AFFINITYMATURATION

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

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IgG7Prof DR Dr Ariyanto Harsono

SpA(K)

IgA

TReg

TGF

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IgG

Th1 Cell

CTL

DTH9Prof DR Dr Ariyanto Harsono

SpA(K)

BAKTIVASI SEL-SEL STRUKTURAL

Nature Rev Immunol 2003; 3: 867-78

Eosinophil

Eosinophil

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CPELEPASAN MEDIATOR

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D EFEK PELEPASAN MEDIATOR PADA TARGET ORGAN

Nature Rev Immunol 2004: 3:234-23712Prof DR Dr Ariyanto Harsono

SpA(K)

Target Organ

IgE-mediated disorder Non IgE-mediated disorder

Skin 

Gastro-intestinal    

Respiratory Tract Multi-system

Urticaria and angioedemaAtopic Dermatitis

Oral Allergy SyndromeGastrointestinal anaphylaxisAllergic eosinophilic gastroenteritis   Asthma; Allergic Rhinitis 

Food-induced anaphylaxisFood associated, exercise-induced anaphylaxis

Atopic DrmatitisDermatitis Herpetiformis

ProctocolitisEnterocolitisAllergic eosinophilic-GEEnteropathy syndromeCeliac DiseaseGI Haemorrhage

Heiner Syndrome

Clinical ManifestationE Symptoms

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Kehamilan = “Th2-disease”

*Anti-oksidan

*Hindari asap rokok

*Probiotik trimester terakhir kehamilan

Pencegahan Primer: Masa Kehamilan

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15Prof DR Dr Ariyanto Harsono SpA(K)

Prevensi Primer dengan susu Formula

FORMULA H.A.Partially hydrolyzed formulas:

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Prof DR Dr Ariyanto Harsono SpA(K)

Tujuan Prevensi Primer

1. Menimbulkan Toleransi Oral

2. Menurunkan prevalensi alergi

17Prof DR Dr Ariyanto Harsono SpA(K)

Formula HA dalam Pencegahan primerBagaimana 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

18Prof DR Dr Ariyanto Harsono SpA(K)

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.

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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)

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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)

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)

Arachidonic Acid (ARA)

Phospholiphase A

Cyccloxygenase Lipoxygenase

Prostaglandine

TXA

Prostacyclin

Leukotriene A

Leukotriene B

Leukotriene C

Omega-3, DHAecosapantaenoic acid

HETE,5-HETE, PAF

PGD2/E2

PGD3 LTC4

LTC523

Prevensi Sekunder

Formula Advanved Hydrolyzed

Formula Soy Isolate

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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 ER because their structure resembles that of the endogenous hormone 17-estradiol.

J. Clin. Invest. 2006 116:16-19

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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

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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)

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

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H2O

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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

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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

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Tujuan Prevensi Sekunder

1. Menurunkan morbiditas

2. Meningkatkan kualitas hidup

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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)

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

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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;40:34337Prof DR Dr Ariyanto Harsono

SpA(K)

LC-PUFA and immune response

ARA DHA

Prostaglandine E2

Push B cells to produce IgE

Th1 Response

pro-inflammatoryanti-inflammatory

Antagonizes ARA

Prostaglandine E2

38Prof DR Dr Ariyanto Harsono SpA(K)

Prostacyclin

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)

Summary

1. In term infants, there are few indications for their use in place of cow milk-based

formula:• (a) for infants with galactosemia and hereditary lactase deficiency (rare) and • (b) in situations in which a vegetarian diet is preferred.

2. For infants with documented cow milk protein allergy, extensively hydrolyzed protein formula should be considered, because 10% to 14% of these infants will also have a soy protein allergy.

3. Most previously well infants with acute gastroenteritis can be managed after

rehydration with continued use of human milk or standard dilutions of cow milk-based formulas. Isolated soy protein-based formulas may be indicated when secondary lactose intolerance occurs.

40Prof DR Dr Ariyanto Harsono SpA(K)

4. Isolated soy protein-based formula has no advantage over cow milk protein-based formula as a supplement for the breastfed infant, unless the infant has 1 of the indications noted previously.

5. Soy protein-based formulas are not recommended for preterm infants.

6. The routine use of isolated soy protein-based formula has no proven value in the prevention or management of infantile colic or fussiness.

7. Infants with documented cow milk protein-induced enteropathy or enterocolitis frequently are as sensitive to soy protein and should not be given isolated soy protein-based formula. They should be provided formula derived from hydrolyzed protein or synthetic amino acids.

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8. The routine use of isolated soy protein-based formula has no proven value in the prevention of atopic disease in healthy or high-risk infants.

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Thank You43