Allergen Immunotherapy & Sublingual Desensitisation

Important: Allergen immunotherapy is a specialist medical treatment suitable only for selected patients with confirmed IgE-mediated allergy, where the relevant allergen has been identified through proper testing and clinical assessment. A thorough specialist evaluation is essential before commencing treatment.

The Shift to Sublingual Immunotherapy (SLIT)

Allergen immunotherapy can be administered in several ways: subcutaneously by injection (SCIT), sublingually under the tongue (SLIT), intralymphatically (investigational), or epicutaneously via skin patches (investigational). In the United Kingdom and across Europe, sublingual immunotherapy has become the predominant route in routine clinical practice.

Since the COVID-19 pandemic, the shift towards SLIT has accelerated further. The requirement for regular clinic attendance with subcutaneous injections — each followed by a mandatory one-hour observation period — proved impractical during periods of healthcare disruption. By contrast, SLIT is self-administered at home on a daily basis after the first supervised dose, making it considerably more accessible, flexible and acceptable to patients. Real-world adherence data and updated EAACI and BSACI guidance both reflect this shift, with SLIT now forming the backbone of immunotherapy provision at our clinic for eligible patients.

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Sublingual immunotherapy — administered at home after the first supervised dose

SLIT involves placing drops or a preparation containing allergen extract under the tongue on a daily basis. The allergen is absorbed through the oral mucosa, where it interacts with tolerogenic dendritic cells and immune cells in the sublingual tissue to begin the process of immune reprogramming. Unlike subcutaneous immunotherapy, SLIT rarely causes systemic reactions; the most common side effects are transient local oral reactions — mild itching or tingling in the mouth or throat — that typically settle within the first weeks of treatment.

SCIT (allergy injections) remains available at our clinic for selected patients with wasp and bee venom allergies. The decision is always made on an individual basis following full specialist assessment.

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▶ 2025 Research Update

A 2025 study published in Immunity (Haspeslagh et al.) demonstrated that IL-10‑producing type 2 innate lymphoid cells (ILC2s) are induced by AIT and are specifically associated with clinical response in allergic rhinitis. Advanced genetic analysis (scCITE-seq) confirmed that in SLIT-treated individuals, these cells show increased activity in retinol metabolism pathways, JAK-STAT signalling and IL-10 receptors — providing a new cellular biomarker of treatment success.

B regulatory cells (Bregs) are also upregulated by AIT, producing IL-10, IL-35 and TGF-β, which promote protective IgG4 blocking antibody responses. Both SLIT and SCIT induce follicular regulatory T cells (Tfr) and IL-10‑producing Tfh cells, whilst suppressing conventional pro-inflammatory Tfh subsets — together creating the sustained immune tolerance that distinguishes AIT from symptomatic medications.

Molecular Allergy Diagnosis and Component-Resolved Diagnostics (CRD)

Why identifying the specific allergenic molecule matters before starting immunotherapy

Traditional allergy testing uses whole allergen extracts to detect IgE sensitisation — a useful starting point, but not always sufficient to guide immunotherapy decisions. Component-resolved diagnostics (CRD) — sometimes called molecular allergy testing — goes further by measuring IgE to individual allergenic proteins (components) within a source. This distinction matters considerably in clinical practice.

For example, a patient with a positive test to house dust mite extract may be sensitised to the clinically important molecules Der p 1 or Der p 2 — or may instead be reacting to a pan-allergen such as tropomyosin, which cross-reacts with crustaceans, cephalopods and other arthropods rather than representing true HDM respiratory allergy. These patients are unlikely to benefit from HDM immunotherapy. Similarly, a positive birch pollen extract test may reflect genuine sensitisation to Bet v 1, or it may reflect cross-reactivity to homologous PR-10 proteins in foods such as apple, hazelnut or celery — in which case pollen immunotherapy can sometimes relieve both respiratory and food-related oral symptoms, but this is not guaranteed.

CRD is therefore particularly valuable in patients with poly-sensitisation — those who test positive to multiple allergen sources — where it is essential to identify which sensitisations are genuinely driving symptoms and which reflect cross-reactivity or co-sensitisation without clinical relevance. Tailoring the immunotherapy formulation to the relevant molecular profile, rather than the crude extract profile alone, is one of the ways in which modern personalised allergy care has advanced.

At our clinic, molecular allergy testing is integrated into the assessment process for all patients where the clinical indication warrants it, and forms part of the EAACI Allergen Immunotherapy Module developed by Professor Paolo Matricardi, Professor Marek Jutel and Professor Mohamed Shamji: EAACI Allergen Immunotherapy Module.

SLIT for Grass Pollen Allergy (Hay Fever)

Grass pollen allergy is the most prevalent inhalant allergy in the United Kingdom, affecting a substantial proportion of the population with seasonal rhinitis, conjunctivitis and, in many patients, allergic asthma. Symptoms typically peak between May and July, driven by the release of pollen from grasses such as timothy, rye, meadow fescue and orchard grass.

Key molecular components: The major allergens in grass pollen are group 1 proteins (e.g. Phl p 1, a cell wall protein), group 5 proteins (Phl p 5, highly specific to grass and the most important target for immunotherapy), and group 2, 4 and 6 allergens. Phl p 1 and Phl p 5 together account for the majority of clinically relevant sensitisation in grass-pollen-allergic patients and are the principal components used to guide immunotherapy decisions. Cross-reactivity exists widely between different grass species through these shared groups, which is why a grass pollen SLIT preparation covering this molecular profile is appropriate for most patients regardless of which specific grass species predominates in their local environment.

SLIT with grass pollen extract has one of the most robust evidence bases of any form of allergen immunotherapy. Large randomised controlled trials have confirmed significant reductions in seasonal symptom scores and rescue medication use. Treatment is typically administered year-round, or started at least four months before the pollen season in the first year. Benefits continue to build across the treatment course and persist for several years after the course ends — a hallmark of disease modification rather than symptom suppression.

Grass pollen SLIT is also clinically relevant for patients with pollen-food syndrome (oral allergy syndrome) driven by cross-reactive PR-10 or profilin proteins, where reducing the underlying grass pollen sensitisation can sometimes ameliorate oral symptoms with certain raw fruits and vegetables — though this effect is variable and dietary modification may still be necessary.

SLIT for House Dust Mite Allergy

House dust mite (HDM) allergy is the most common cause of perennial (year-round) allergic rhinitis and is a major driver of allergic asthma in the UK. The principal culprits are Dermatophagoides pteronyssinus and Dermatophagoides farinae, microscopic arachnids that thrive in warm, humid domestic environments — particularly in bedding, upholstered furniture and carpeting.

Key molecular components: Der p 1 (a cysteine protease) and Der p 2 (a structural homologue of MD-2 with TLR4-potentiating activity) are the two dominant major allergens of D. pteronyssinus, together accounting for the majority of clinically significant HDM sensitisation. Der p 1 has the additional property of disrupting airway epithelial tight junctions through its protease activity, facilitating allergen penetration across the mucosal barrier and amplifying the sensitisation process. Der p 23, a recently identified peritrophic membrane protein, is now recognised as a third important component in a subset of HDM-allergic patients. Molecular testing for Der p 1 and Der p 2 (and where relevant, Der p 23) is valuable because some patients who test positive to HDM extract are in fact sensitised only to pan-allergens such as tropomyosin (Der p 10), which cross-reacts with crustaceans and other invertebrates rather than conferring true HDM respiratory allergy — and these patients are not candidates for HDM immunotherapy.

HDM SLIT has been evaluated in some of the largest immunotherapy trials ever conducted. Data involving over 9,000 patients across 25 countries and 15 years of follow-up confirm its efficacy in reducing nasal symptoms and medication use, and in improving asthma control in patients with HDM-associated allergic asthma alongside rhinitis. In 2025, NICE issued updated technology appraisal guidance confirming that HDM SLIT is the first immunotherapy treatment to achieve formal disease-modification recognition in the UK — an important milestone reflecting the quality of the evidence base.

HDM SLIT is appropriate for patients aged twelve and over with persistent moderate-to-severe HDM allergic rhinitis that is inadequately controlled by standard medications. For adults with HDM-associated allergic asthma, SLIT may reduce inhaled corticosteroid requirements whilst maintaining asthma control — but the asthma must be well controlled before starting treatment, as uncontrolled asthma is a contraindication.

SLIT for Birch Pollen Allergy

Silver birch (Betula pendula) is the dominant tree pollen allergen in northern and central Europe, including the United Kingdom, causing hay fever symptoms typically during March and April. It is a particularly important allergen in clinical practice because its major allergenic protein, Bet v 1, is a member of the PR-10 protein family — a group widely distributed across plant foods and other tree pollens.

Key molecular components: Bet v 1 is the dominant major allergen of birch pollen, with a sensitisation frequency exceeding 90% among birch-allergic individuals — comparable to Fel d 1 from cat and Der p 1 from house dust mite in terms of its dominance within its source. Because Bet v 1 shares structural homology with PR-10 proteins in foods such as apple (Mal d 1), hazelnut (Cor a 1), peach, pear, celery and soya, many birch-pollen-sensitised patients develop oral allergy syndrome (pollen-food syndrome) with these foods. Bet v 2 (profilin) and Bet v 4 (calcium-binding protein) are minor allergens that can cause additional cross-reactivity with other pollens and foods. Molecular testing to confirm primary Bet v 1 sensitisation — rather than cross-reactive PR-10 positivity driven by another pollen — is important before initiating birch pollen immunotherapy.

Sublingual immunotherapy with birch pollen extract is available for adults with birch pollen allergic rhinitis. For younger patients, treatment may be offered under specialist guidance. Clinical trial data confirm its efficacy in reducing seasonal nasal and ocular symptoms. Additionally, by reducing sensitisation to Bet v 1, birch pollen SLIT can in some patients attenuate oral allergy syndrome symptoms with cross-reactive foods — a secondary benefit not achievable with antihistamines or avoidance alone — though the extent of this improvement varies between individuals and food avoidance may still be needed.

A full molecular allergy assessment is especially valuable in birch-sensitised patients presenting with complex multi-food oral symptoms, to determine which allergens are genuinely driving the picture and whether birch pollen SLIT is the appropriate primary intervention.

SLIT for Cat Allergy

Cat allergy is one of the most prevalent indoor allergen sensitivities, affecting an estimated 10–20% of the general population in industrialised countries, with a global incidence that has been rising over recent decades. Cats are the second most common source of indoor inhalant allergens after house dust mites. Importantly, cat allergens — particularly Fel d 1 — are extremely small, lightweight particles that remain airborne for extended periods and adhere readily to clothing and furnishings, meaning that exposure is not confined to households that own cats. Cat allergens are routinely detected in schools, workplaces and public transport.

Key molecular components: Fel d 1 is the dominant major cat allergen, present in cat skin, sebaceous glands, saliva and perianal glands. It is a uteroglobin-family protein and sensitises over 90% of cat-allergic individuals — making it the primary molecular target for diagnosis and immunotherapy selection. Elevated specific IgE to Fel d 1 is associated with increased risk of asthma in cat-allergic children and with concurrent sensitisation to multiple animal allergens. Fel d 2 (serum albumin) is a minor allergen that cross-reacts with albumins from other species, including dog (Can f 3), and may be responsible for reactions to cat and dog in patients who own neither. Fel d 4 (a lipocalin) shows cross-reactivity with the major dog lipocalin Can f 1 and the horse allergen Equ c 1, which can complicate the clinical interpretation of multiple animal sensitisations. Recombinant Fel d 1 is now available for in vitro IgE testing and is increasingly replacing whole-extract testing in specialist practice.

SLIT with standardised cat dander extract has been evaluated in double-blind placebo-controlled trials. A landmark study demonstrated a 62% reduction in nasal and bronchial symptoms during cat exposure challenge in the active SLIT group, with no systemic adverse reactions reported. A three-year course of sublingual allergen immunotherapy with lyophilised cat epidermal allergen extract has also been shown to produce significant clinical improvement and a reduction in Fel d 1-specific IgE levels in children with allergic rhinitis and asthma, confirming its disease-modifying potential in this age group.

Cat allergen SLIT is most appropriate for patients who have unavoidable ongoing exposure — for instance, those who own cats, live with family members who do, or have occupational exposure. As with all forms of immunotherapy, complete avoidance of the allergen during treatment makes it unlikely to succeed. A specialist assessment is required to confirm Fel d 1 sensitisation, assess comorbid asthma control and determine suitability.

SLIT for Dog Allergy

Dog allergy is increasing in clinical frequency as dog ownership rises worldwide. Like cat allergens, dog allergens spread extensively through the environment and can be found in homes, schools and public spaces regardless of whether dogs are present. Dog-allergic patients frequently present with rhinitis, conjunctivitis, asthma and, less commonly, urticaria or angioedema following contact.

Key molecular components: Dog allergen biology is considerably more complex than cat, with multiple clinically important molecules. Can f 1 and Can f 2 are the two major lipocalin allergens, produced in the tongue epithelial tissue and salivary glands respectively. Between 50 and 64% of dog-allergic individuals are sensitised to Can f 1, and among those sensitised, up to 80% have concurrent respiratory symptoms including asthma — making Can f 1 a key determinant of clinical severity. Can f 5 is a kallikrein protein with particular significance because it is produced in the prostate gland and is present in male dogs only; patients sensitised primarily to Can f 5 may be substantially less symptomatic around female or neutered dogs, which has practical management implications. Can f 3 is a serum albumin that cross-reacts with cat albumin (Fel d 2), horse and other mammalian albumins. Can f 6 is another lipocalin showing cross-reactivity with Fel d 4 and the horse allergen Equ c 1. Measuring specific IgE to the individual molecular components of dog allergy is therefore clinically important in determining the full sensitisation profile and selecting the appropriate allergen for immunotherapy.

SLIT with dog allergen extract is available for selected patients with confirmed dog sensitisation. The evidence base is somewhat less extensive than for cat, grass pollen or HDM, partly because dog allergen extract quality has been more variable historically and there is no single dominant allergen comparable to Fel d 1 or Bet v 1. Nonetheless, studies support clinical benefit from dog allergen immunotherapy in appropriately selected patients, and molecular diagnostics significantly improve patient selection for this indication.

As with cat, dog allergen SLIT is only considered where exposure cannot be eliminated — typically in patients who own dogs or have frequent unavoidable contact. A specialist assessment including molecular allergen profiling is recommended prior to commencing treatment.

SLIT for Alternaria Mould Allergy

Alternaria alternata is the clinically most important outdoor mould allergen in the UK and Europe. Its spores are released into the outdoor air predominantly during dry, warm conditions in late summer and early autumn, with peak counts between July and October. Alternaria allergy carries particular clinical significance because of its strong association with severe, potentially life-threatening asthma — sometimes referred to as ‘thunderstorm asthma’ — and it is considered an independent risk factor for asthma severity and for fatal asthma attacks in sensitised individuals.

Key molecular components: Alt a 1 is the dominant major allergen of Alternaria alternata, with a sensitisation frequency of approximately 90% among Alternaria-allergic patients — a degree of dominance comparable to Bet v 1 from birch and Fel d 1 from cat. This molecular dominance has made standardisation of Alternaria extracts for both diagnostic testing and immunotherapy possible, and Alt a 1 content is now used as a quality benchmark for Alternaria preparations. Alternaria also contains enolase and heat-shock proteins which show some cross-reactivity with other moulds, notably Cladosporium herbarum — however, there is no dominant major allergen for Cladosporium, and immunotherapy is not currently recommended for it.

Among all mould allergens, Alternaria alternata is currently the only species for which allergen immunotherapy is recommended in international guidelines, with sufficient controlled trial evidence in both children and adults to support its use. Studies show good tolerability and similar effectiveness for SLIT compared with subcutaneous AIT for Alternaria, supporting SLIT as the preferred route. Immunotherapy can reduce rhinitis and asthma symptoms and — given the potentially serious consequences of uncontrolled Alternaria-driven asthma — may be particularly worthwhile in patients with significant asthma who have confirmed Alt a 1 sensitisation.

An important practical note: mould allergen extracts contain proteases that can degrade other allergen extracts if combined in the same preparation. If a patient requires immunotherapy for both a mould and another allergen (e.g. HDM), international guidelines require that these be administered as separate preparations rather than combined in one vaccine.

SLIT for Cow Epidermal Allergen (Occupational Allergy)

Allergy to cow epidermal allergens is an important but less commonly considered occupational condition, primarily affecting farmers, veterinary surgeons, agricultural workers and others with regular close contact with cattle. Symptoms include allergic rhinitis, conjunctivitis, asthma and urticaria triggered by exposure to cow dander, hair, urine or saliva, and can significantly impair occupational capacity and quality of life in affected individuals.

Key molecular components: The major cow epithelial allergens include Bos d 2 (a lipocalin, produced predominantly in cow skin and hair follicles, and the dominant major allergen for cow-related occupational respiratory allergy), and Bos d 3 (a calcium-binding protein). Bos d 6 is the bovine serum albumin, which cross-reacts with albumins from other species including horse, cat, dog and pig — meaning that some patients apparently sensitised to multiple animals may in fact have a single albumin-driven cross-reactivity rather than independent sensitisations. This distinction is clinically important and is a key application of molecular allergy testing in this group. Bos d 5 (beta-lactoglobulin) is relevant primarily in cow’s milk allergy and is of less relevance in occupational respiratory sensitisation, though it may contribute in farm workers with combined skin and respiratory symptoms.

SLIT with cow epidermal allergen extract represents a specialist application of allergen immunotherapy for this occupational indication. It is not commonly required in general allergy practice and is considered only in rare cases where: cow allergen sensitisation has been confirmed by skin prick testing and/or specific IgE including molecular components; respiratory symptoms are clinically significant and occupationally disabling; avoidance is not feasible (as the patient’s livelihood depends on working with cattle); and asthma, where present, is well controlled.

The evidence base for cow allergen immunotherapy is more limited than for the established inhalant allergens described above, and this treatment is offered only following careful individual assessment by a specialist with experience in occupational allergy.

Latest Evidence: 2025–2026 Research Advances

A summary of clinically significant developments informing current practice

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Pollen-Food Syndrome: For patients with mild oral symptoms related to pollen-food cross-reactivity (oral allergy syndrome), allergen immunotherapy targeting the primary respiratory allergy — such as birch pollen — can sometimes alleviate food-related symptoms. This occurs because immune modulation through immunotherapy may reduce cross-reactive responses to structurally similar proteins in certain raw fruits and vegetables. However, this improvement is not guaranteed and many patients still need to avoid raw forms of trigger foods even after successful pollen immunotherapy.

Who May Be Suitable for Immunotherapy?

The decision to commence immunotherapy must be based on the entire clinical picture — not a test result alone. It is generally considered when:

Adherence — The Critical Success Factor: Good adherence is the single most important modifiable factor in the outcome of immunotherapy. SLIT requires daily administration, typically for three to five years. Modern allergy care uses structured follow-up, symptom tracking and patient-reported outcome measures to support adherence and monitor response. At our clinic, we provide a clear treatment plan and regular review appointments throughout the course.

Practical Information: Duration, Results and Safety

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Duration of Treatment

A full course of allergen immunotherapy typically lasts three to five years. Current evidence suggests that a four-year SLIT course may be optimal, providing up to eight years of continued immune tolerance after completion. Stopping treatment early significantly reduces the chance of achieving lasting benefit. As treatment is long-term, careful reflection before starting is important — particularly for patients who travel frequently or may need to relocate.

When Will I Notice a Difference?

Most patients begin to notice a meaningful reduction in symptoms after six to twelve months. Clinical improvement continues to build across the first two to three years. Immunotherapy is not a rapid treatment — symptom-relieving medicines are often still needed in the early phase, and patients should approach the first season of treatment with realistic expectations.

Side Effects and Safety

SLIT — The most common side effects are local oral reactions: mild itching, tingling or swelling in the mouth or throat, most noticeable in the early weeks of treatment. These are usually transient and settle with continued use. Systemic reactions are very rare. The first dose is always supervised. Subsequent home doses should be taken exactly as prescribed; any troublesome symptoms should be discussed promptly with your specialist. SLIT is not appropriate for patients with eosinophilic oesophagitis, active oral inflammation (thrush, ulcers, lichen planus) or dental wounds from recent procedures.

SCIT — When subcutaneous injection immunotherapy is used, all injections are given in a clinical setting with a mandatory one-hour observation period and immediate access to emergency treatment. Physical activity, alcohol and hot baths should be avoided for six to eight hours afterwards. During the grass pollen season, maintenance doses are typically reduced by 25% to account for background exposure.

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Our Approach to Immunotherapy

Not every patient presenting with allergy symptoms is a candidate for immunotherapy. At our London clinic, every patient considering AIT undergoes a thorough clinical evaluation including a full allergy history, skin prick testing and/or specific IgE blood testing, and — where indicated — component-resolved diagnostic (molecular) allergy testing to identify the most clinically relevant allergen molecules, exclude cross-reactivity as the primary driver, and guide the selection of the appropriate treatment preparation.

We discuss the evidence for each available treatment option, realistic expectations for benefit, the demands of the treatment course and potential risks — so that every patient can make a fully informed decision. If immunotherapy is initiated, we provide a structured follow-up programme to monitor progress, support adherence and adjust the plan when necessary.

Our practice remains committed to evidence-based care and continuing medical education, staying current with EAACI, BSACI and ARIA guidelines and incorporating the latest 2025–2026 clinical evidence into our protocols.

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Is immunotherapy available on the NHS?

Access to AIT on the NHS is subject to local commissioning decisions and specialist assessment. Availability varies considerably across different parts of the UK, and waiting times can be lengthy. At our clinic, we offer immunotherapy on a private basis, allowing timely assessment and access to the full range of licensed preparations.

Can children receive immunotherapy?

Yes. SLIT is available from age five for grass pollen allergy and from age twelve for house dust mite. Other preparations may be appropriate in younger children under specialist guidance. Early treatment is particularly compelling in paediatric patients because of its documented ability to prevent new sensitisations and the progression from rhinitis to asthma.

Do I still need antihistamines whilst on immunotherapy?

During the early phase, symptom-relieving medicines are often still needed, particularly during the pollen season. A reduction in rescue medication use over time is one of the measurable outcomes of successful AIT, and most patients find their need for antihistamines and nasal sprays reduces significantly as the course progresses.

What happens if I miss a dose?

Occasional missed doses are unlikely to compromise the overall course, but regular gaps significantly reduce the chance of achieving lasting benefit. If you have missed several weeks of treatment, please contact our clinic before resuming — in some situations, the dosing schedule may need to be adjusted.

Will immunotherapy cure my allergy permanently?

Immunotherapy is not guaranteed to produce complete tolerance in every patient, but it is the only available treatment that produces benefit continuing after the course ends. Evidence supports sustained clinical benefit for several years post-treatment in the majority of responders. The ideal endpoint is a negative skin prick test, though this is achieved in a minority of patients; many others achieve a good symptomatic and functional response without complete tolerance.

Can immunotherapy prevent the development of asthma?

Evidence consistently supports AIT’s role in preventing the progression from allergic rhinitis to asthma, particularly in children and young adults. This remains one of the most compelling reasons to consider early treatment in suitable patients, and represents a genuine advantage over symptom-suppressing medications that have no effect on disease trajectory.

Medical Disclaimer: The information on this page is intended for general educational purposes only and does not constitute medical advice or replace individual clinical consultation. Allergen immunotherapy is a specialist medical treatment appropriate only for selected patients following thorough assessment. Suitability, dosing and monitoring must always be determined by a qualified specialist. References to 2025–2026 research reflect published literature at the time of writing. Patients are encouraged to discuss their individual circumstances with their treating clinician.