A Brief Insight into the Transition from Allergy to Autoimmunity

The long-term risk of developing an autoimmune disorder is significantly higher in patients with allergies,¹ which may explain why the prevalence of both diseases is increasing in parallel.

But why is it that Th2- and Th1-mediated autoimmune diseases can occur concurrently when, in theory, they should balance and even counteract each other?²

Recent evidence points to the differentiation of naïve CD4+ T cells or Th subsets. Beside the Th1/Th2 subset, several additional Th subsets have been identified, including Th17, regulatory T cells (Treg), as well as lineage-specific inflammatory cytokines involved in allergy and autoimmune disease (see Figure 1). Allergies are Th2-dominant presentations, whereas autoimmune diseases are Th17 dominant (both are also known as a Th1/Th2 and Treg/Th17 imbalances, respectively).^3-7  Th17 cells and Treg cells have opposing actions, with Th17 causing autoimmunity and inflammation, while Treg cells maintain immune homeostasis by inhibiting immune responses and autoreactive effector T cells.⁸

Figure 1 | CD4+ cell differentiation, effector function & lineage-specific cytokines.⁷

Short-term exposure to exogenous allergens causes acute allergic inflammation in allergy sufferers, which is characterized by IgE-dependent mast cell (MC) and basophil degranulation, Th2 cell activation, and diminished or no Th1 activity. However, when exposure to exogenous allergens becomes chronic, it can lead to prolonged allergic inflammation, autoantigen release due to tissue damage and activation of Th1 cells which then collectively promote IgE independent tissue damage and inflammation. Overall, the transition from acute to chronic allergic inflammation results in Th1 activation in the auto-sensitized allergic patient (see Figure 2), increasing their risk of developing an autoimmune disorder.²

Figure 2 | The transition from allergy to autoimmunity.²

Herbal Medicines and Nutritionals That Target Underlying Immune Mechanisms Involved in Allergies and Autoimmune Disease

Resetting the mechanisms described above is an important clinical approach to controlling autoimmunity in allergy patients suffering from chronic allergies. This may be achieved by using herbal and nutritional ingredients that have a demonstrated ability to inhibit Th1 and Th17 T cells - as well as their corresponding cytokines – while also promoting Treg cell formation.⁶ Moreover, this approach perfectly complements a formulated treatment plan that addresses existing allergies, as reducing MC activity is also a treatment goal in autoimmune diseases due to their pivotal role in the inflammatory process and interactions with Treg and Th17 cells.⁹

Hemidesmus indicus

Hemidesmus indicus (Hemidesmus), commonly known as Indian Sarsaparilla, is used in Ayurvedic medicine as a depurative or blood cleanser to relieve skin inflammation, support skin health,^10,11 and treat rheumatism.¹² It is mostly known for its anti-inflammatory and immunomodulatory activities^12,13 and is used as an immune depressant to treat autoimmune conditions such as rheumatoid arthritis (RA) in traditional Western herbal medicine.¹⁴

Rehmannia glutinosa

Rehmannia glutinosa (Rehmannia) is used in traditional Chinese medicine as an immune-modulating, anti-inflammatory and antiallergic herb. Some constituents of the root are thought to have immune-stimulating effects, while others are considered immunosuppressive.¹⁵ It is used to treat RA, asthma and urticaria in traditional Western herbal medicine.¹⁴

Curcuma longa (Curcumin)

Curcuma longa (Turmeric) and its active component curcumin exhibit immune modulating, anti-inflammatory and antiallergic activity.^16,17 Curcumin modulates the immune system by inhibiting Th1 and Th17 and promoting Treg,^6,17 while simultaneously downregulating a myriad of inflammatory cytokines.¹⁸ Its potent anti-inflammatory activity has been demonstrated in a wide range of clinical trials.16 However, due to its poor absorption, Turmeric should be taken as a phosphatidylcholine (phospholipid) complex, which has been shown to greatly enhance bioavailability, and thus clinical effects.^19-21

Baical skullcap (Baicalin)

Scutellaria baicalensis (Baical skullcap) and its active component baicalin have immune-modulating, anti-inflammatory and antiallergic activity.^14,22 They inhibit Th1 and Th17 mediated processes in the body and promote Treg cell differentiation.⁶ Preliminary evidence has demonstrated benefits in psoriasis and it is commonly used for chronic inflammatory conditions.²²

Vitamin D3

Both vitamin D deficiency and vitamin D genetic polymorphisms have been shown to be associated with an increased incidence of autoimmune disease.²³ Together, vitamin D and vitamin D receptor (VDR) signalling play a suppressive role in autoimmunity. Specifically, they promote dendritic cell and Treg cell differentiation, reduce Th17 cell response and decrease inflammatory cytokine secretion.²⁴ Vitamin D deficiency and insufficiency is however a prominent global health issue that affects over one billion children and adults worldwide.²⁵ Re-establishing adequate tissue levels of vitamin D is therefore an important clinical goal.

Table 1 | Mechanisms of Action of Selected Herbs & Vitamins Relevant to Allergies & Autoimmune Disease

Clinical Take-away

Aiming to reset the mechanisms that promote autoimmunity in allergy patients, such as a T helper and Treg/Th17 imbalance, is an important tool in the toolbox of the astute clinician. Moreover, herbal and nutritional actives such as Hemidesmus, Rehmannia, Turmeric, Baical skullcap and vitamin D3 not only demonstrate this ability, but also address many of the common underlying inflammatory and immunological processes that are characteristic of allergies and autoimmune disease.

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