inflammation & autoimmunity

allergies

NFATC2

Th2 Dysregulation & Allergies (NFATC2)

Written by Shany Lahan, MS (Neuroscience) on October 29th, 2020

NFATC2 is a protein involved in type 2 immune response (Th2) regulation. Read more to learn about the association between an NFATC2 variant and allergies.

Summary

NFATC2 is a protein that can regulate the production of type 2 immune response (Th2) proteins. A variant of NFATC2 may play a role in allergic diseases by altering production of NFATC2 and increasing levels of Th2 proteins. Lifestyle and supplement modifications may counteract the effects of this variant by decreasing Th2 protein levels.

NFATC2 and Allergies

NFATC2 is a protein involved in regulating the production of other proteins, including IL-4 and IL-13 [R, R].

IL-4 and IL-13 are released by type 2 immune response (Th2) cells. Many scientists consider elevated Th2 activity to underlie a number of allergic diseases [R].

Indeed, the production of IL-4 and IL-13 has been shown to enhance the responsiveness of the airway to allergens (allergy-inducing substances). These immune system proteins have also been linked to elevated release of a type of antibody called IgE — an early step in allergic reaction progression [R, R, R, R].

Interestingly, both increased and decreased production of NFATC2 has been linked to dysregulated Th2 activity and consequent susceptibility to allergic diseases, such as asthma. It’s therefore likely that NFATC2 needs to be produced in optimal amounts in order to properly regulate immune responses [R, R].

Variants of NFATC2 have been associated with allergic diseases. These variants may increase or decrease NFATC2 production, which may result in dysregulated Th2 activity, enhanced airway responsiveness to allergens, and increased production of IgE antibodies [R, R].

Your NFATC2 Results for Allergies

SNP Table

variant	genotype	frequency	risk allele
rs6021270

Primary SNP:

NFATC2 rs6021270

‘T’ = Increased risk of allergies, relative to ‘C’
‘C’ = Decreased risk of allergies, relative to ‘T’

Recommendations

Lifestyle

Allergy Immunotherapy

Allergy immunotherapy consists of administering a weakened allergen (such as pollen, dust mites, or dog dander) to help develop tolerance or desensitization to said allergen. This treatment can be oral (under-the-tongue allergy tablets) or injected (allergy shots) [R, R, R, R, R].

Bee sting therapy is recommended as the first-line treatment for the prevention of severe allergic reactions in people allergic to the venom of bees and other insects of the same order (Hymenoptera). This may be due to the ability of bee sting therapy to lower Th2 activity, including lowering IL-4 production [R, R, R].

Multiple trials attest to the effectiveness and safety of bee sting therapy. Unfortunately, the venom must be repeatedly administered at 3-month intervals to maintain its effects on the immune system [R, R, R, R, R, R, R, R, R].

In a study of children with cow milk allergy, oral immunotherapy was found to desensitize approximately 70% of the allergic children. Desensitization was linked to decreases in IL-13 release, as well as decreases in IgE antibody levels. Moreover, oral immunotherapy eliminated any immune response differences originally observed between children with cow milk allergy and non-allergic children [R].

Allergy immunotherapy may improve allergies by lowering Th2 activity via decreased IL-4 and IL-13 production, and by lowering IgE antibody levels.

Diet

Mediterranean Diet

A meta-analysis linked adherence to the Mediterranean diet with a slightly reduced incidence of wheezing and asthma [R].

In one study, Mediterranean diet adherence was found to lower levels of allergy-associated immune system proteins, such as IL-4, in children with asthma [R].

The Mediterranean diet states that olive oil should be the main source of added fat in the diet. In a cell-based study, olive oil was reported to decrease production of IL-4 [R].

Adherence to the Mediterranean diet may improve allergies by lowering production of the Th2-related protein IL-4.

Supplements

Probiotics

Probiotics are live strains of beneficial bacteria that may improve allergies by reducing Th2 activity, including the production of IL-4 and IL-13 [R].

Indeed, probiotics such as Lactobacillus (L.) paracasei, L. acidophilus, L. plantarum, L. casei, L. gasseri, Bifidobacterium (B.) longum, and B. animalis were found to improve hay fever in multiple trials. Moreover, L. rhamnosus, L. johnsonii, and Clostridium (C.) butyricum enhanced the effectiveness of immunotherapy for pollen and dust mite allergies [R, R, R, R, R, R, R, R, R, R, R, R, R].

In a randomized controlled trial focused on children with asthma and hay fever, 8-week daily supplementation of L. gasseri significantly lowered levels of IL-13 [R].

In people with asthma, L. salivarius and B. breve reduced the production of inflammatory proteins, while C. butyricum combined with immunotherapy helped improve asthma symptoms [R, R].

Preliminary research in adults and children with an allergy to cow milk suggests that the potential for L. rhamnosus to modulate immune system activity may help prevent allergic reactions. This probiotic also enhanced the effectiveness of immunotherapy for peanut allergy [R, R, R].

Other probiotics may help by fermenting the food proteins that cause allergies. For instance, L. helveticus, L. delbrueckii, and L. fermentum successfully reduced the allergenic potential of cow milk and propolis in several studies [R, R, R, R].

Probiotics may improve allergies by reducing Th2 activity, including the production of IL-4 and IL-13.

Shany Lahan

MS (Neuroscience)

Shany received her MSc in Neuroscience from Western University.

Prior to joining SelfDecode, Shany conducted research related to Alzheimer’s disease, and taught science to undergraduate students. She believes that research should be accessible to everyone, regardless of scientific background. Shany joined SelfDecode with a mission to help others optimize their health and wellbeing – as well as help them understand the science behind it all.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

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