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New study identifies unique peptides with tolerogenic potential

New study, published in August 2018 in Clinical & Experimental Allergy, highlights the presence of specific protein fragments (peptides) in Nutricia’s partially hydrolysed protein formula (pHF)1. These peptides have the potential to support immune tolerance development to cow’s milk protein2, and therefore support reduction in allergy development in infants at risk of allergy.

Learn more about this study and about Nutricia’s new research program to support immune tolerance development in the attached summary and in our publication library.

Hydrolysed protein and allergy risk management.

The prevalence of allergic diseases worldwide is rising dramatically in both developed and developing countries, affecting 30 to 40% of the world population today3, and cow’s milk protein allergy (CMPA) is one of the key food allergies in infants and children4. Forming sustainable prevention strategies to reduce the growing burden of allergic diseases in infants and children remains the best long-term approach to manage the allergy epidemic.

The primary recommendation to prevent allergic disease is exclusive breastfeeding for 4-6 months. If breastfeeding is not possible, international guidelines recommend a hypoallergenic formula (i.e. partially hydrolysed cows’ milk protein formula) for infants at high risk of allergy (based on family history of allergy)5. This has been investigated in several clinical trials in the last decades showing a potential to reduce the risk of developing atopic dermatitis/eczema in high risk infants, compared to intact protein formula6,7.

Immune tolerance is an active and natural response of the immune system, normally generated in healthy infants not showing an allergic reaction. Immune tolerance is the ultimate end goal as the immune system recognizes the protein (e.g. cow’s milk protein) as harmless substance, and the protein is tolerated8. Thus, researchers believe that immune tolerance can be promoted by the exposure to low dose cow’s milk allergens as found in formulas based on partially hydrolyzed protein9,10.

Tolerogenic capacity of peptides.

In a partially hydrolysed whey protein formula, the cow’s milk protein is enzymatically hydrolysed (broken down in smaller fragments, so-called peptides) with the goal to reduce protein size and as such the potential allergenicity of the proteins.

The concept of partially hydrolysed cow’s milk protein (pHF) formula aims at securing the balance in reducing allergenicity of the protein, while maintaining tolerogenic capacity. As each hydrolysed infant formula is manufactured differently, not all partial hydrolysed formulas are the same.

As depicted in figure 1, an intact protein can contain fragments that would elicit an allergic response (purple epitope). In addition, it can contain T cell epitopes (in blue) that under the right circumstances would induce tolerance by activating regulatory T cells (T regs). The presence of these epitopes in a partially hydrolysed infant formula is thus essential for the induction of cow’s milk-specific T regs and subsequent oral tolerance development.

Nutricia’s unique hydrolysate ensures reduced allergenicity while maintaining the capacity to support the natural development of immune tolerance.

Our new study1 confirms the identification of specific peptide fragments, with the potential to have tolerogenic capacity2.

These specific peptides have been found consistently present in Nutricia’s pHP formula, suggesting that this infant formula under the right circumstances may stimulate immune tolerance development.2,11–15

New research programme on immune tolerance development.

In parallel of reducing the allergenicity of the protein by hydrolysis together with ensuring the presence of specific peptides, we believe that stimulating a favorable microbiota via pre- and probiotic supplementation is an effective strategy to support oral tolerance development and therefore prevent development of the allergic response.

To support our conviction, we have developed a nutritional concept for which we have convincing and proven indications for the individual effective engines that this will effectively reduce the incidence of allergy in infants at risk of allergy. This infant nutrition concept is based on our specific hydrolysed protein with tolerogenic capacity, combined with a specific mixture of pre- and probiotics “pHF synbiotics”.

We have embarked on a clinical research programme to demonstrate the safety and efficacy of pHF with synbiotics. Learn more about the programme here.

1.
Gouw, J. W. et al. Clin Exp Allergy, Identification of Peptides with Tolerogenic Potential in a Hydrolyzed Whey‐Based Infant Formula, 2018. doi:10.1111/cea.13223.
2.
Meulenbroek et al. Pediatr Allergy Immunol. 24(7):656-64 (2013).
3.
Pawankar, R., et al., World Allergy Organisation (WAO): White book on allergy. 2011, World Allergy Organisation: Wisconsin.
4.
Fiocchi, A., et al., World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines. Pediatr Allergy Immunol, 2010. 21 Suppl 21: p. 1-125.
5.
Muraro, A. et al. EAACI food allergy and anaphylaxis guidelines. Primary prevention of food allergy. Allergy 69, 590-601, doi:10.1111/all.12398 (2014).
6.
Szajewska, H. and A. Horvath, A partially hydrolyzed 100% whey formula and the risk of eczema and any allergy: an updated meta-analysis. World Allergy Organ J, 2017. 10(1): p. 27.
7.
Szajewska, H. and A. Horvath, Meta-analysis of the evidence for a partially hydrolyzed 100% whey formula for the prevention of allergic diseases. Curr Med Res Opin, 2010. 26(2): p. 423-37.
8.
Weiner, H.L., Oral tolerance, an active immunologic process mediated by multiple mechanisms.J Clin Invest, 2000. 106(8): p. 935-7.
9.
Flohr, C. & Mann, J. New approaches to the prevention of childhood atopic dermatitis. Allergy 69, 56-61, doi:10.1111/all.12343 (2014).
10.
Host, A. & Halken, S. Hypoallergenic formulas–when, to whom and how long: after more than 15 years we know the right indication! Allergy 59 Suppl 78, 45-52, doi:10.1111/j.1398-9995.2004.00574.x (2004).
11.
van Esch et al. Pharmanutrition 5, 1-7 (2017).
12.
van Esch, B. C. et al. Pediatr Allergy Immunol 22, 820-826 (2011).
13.
van Esch, B. C. et al. Toxicol Lett 220, 95-102, (2013).
14.
Boyle, R. J. et al. Allergy 71, 701-710 (2016).
15.
van Esch, B. C. et al. Pediatr Allergy Immunol 21, e780-786 (2010).