Supporting Evidence

The following abstracts represent a few key studies and reviews conducted that support what we have clinically experienced in relation to dose, mechanism, duration, the use of multiple antigen and the treatment of food allergies with the La Crosse Method™ Practice Protocol.


Emerging concepts of sublingual immunotherapy for allergy
Theodoropoulos, D., Morris, M., Morris, D. Drugs of Today 2009, 45(10): 737-750

Key Points:

  • SLIT administered multiple times daily reduces peak-and-trough effects of SCIT.
  • Dosing should be adjusted to skin reactivity under the premise that adverse and local reactions define a level of tolerance.

Allergen immunotherapy: Where is it now?
Nelson, H. The Journal of Allergy and Clinical Immunology, 2007: 769-777

Key Points:

  • In a review of 48 randomized, mostly double-blind SLIT trials, it was found that doses over a 1000-fold range were reported to produce clinical improvement.
  • The rate of success did not increase as the dose increased, suggesting a limited absorptive capacity of the sublingual mucosa.
  • Large doses may be more effective in short-term studies, however the frequency and duration of treatment are important and have shown lower doses have been effective and are important determinants of SLIT response.

Sublingual immunotherapy: Dosing in relation to clinical and immunological efficacy
Larenas-Linnemann, D. Allergy Asthma Proc 2008; 29: 130-139 doi: 10.2500/aap.2008.29.3093

Key Points:

  • A straight dose-effect relationship does not exist — so many other variables have to be taken into account such as quality of extract, dosing frequency and duration of treatment.
  • SLIT is a procedure whose time has come and will allow us to broaden our indications for the only causative treatment of allergies and is still too underused at the present time.

High-dose sublingual immunotherapy: too much of the good?
Annals of Allergy, Asthma and Immunology, 97(2)125

Key Points:

  • High allergen doses have been shown to stimulate TH1 CD4+ cells, whereas low doses induce TH2 responses.
  • It might be speculated that the oral mucosa and the immunocompetent cells are saturated already at low allergen concentrations; thus, a quasipermanent confrontation with an antigen by multiple daily administrations could be more effective in the promotion of a long-lasting T-cell response.


Advances in upper airway diseases and allergen immunotherapy
Nelson, H. JACI, 2007; 872-880

Multiple daily administrations of low-dose sublingual immunotherapy in allergic rhinoconjunctivitis
Bordignon, V., Burastero, S., Annals of Allergy, Asthma & Immunology 2006;9:158-163.

Key Points:

  • The absorptive capacity of the sublingual area is limited and better results might be obtained by frequent dosing.
  • The number of daily dosing correlates to SLIT efficacy and may be a more important factor over dosage.

Multiple Antigens

Emerging concepts of sublingual immunotherapy for allergy
Theodoropoulos, D., Morris, M., Morris, D. Drugs of Today 2009, 45(10): 737-750.

Effects of sublingual immunotherapy for multiple or single allergens in polysensitized patients
Marogna, M., Spadolini, I., Massolo, A., Zanon, P., Berra, D., Chiodini, E., Canonica, G.W., Passalacqua, G. Annals of Allergy 2007; 98, 3:274-280.

Key Points:

  • Patients that received SLIT for grass and birch had greater improvement in clinical symptoms and inflammation was significantly greater than in patients treated with SLIT for single allergen.


Emerging concepts of sublingual immunotherapy for allergy
Theodoropoulos, D., Morris, M., Morris, D. Drugs of Today 2009, 45(10): 737-750.

Key Points:

  • Frequent and regular administration of sublingual immunotherapy may prove conducive to effector cell conditioning and may be the reason SLIT, titrated against skin test reactivity, is devoid of the side effects of SCIT and their associated failures.

Dendritic cells as potential targets for mucosal immunotherapy
Allam, J., Bieber, T., Novak, N. Current Opinion in Allergy and Clinical Immunology 2009, 9:554-557.

Key Points:

  • Oral mucosal antigen-presenting cells (APCs) such as dendritic cells play a pivotal role in the SLIT mechanism as they are critical for initiation and modulation of T-cell immune response.

Oral tolerance, food allergy, and immunotherapy: Implications for future treatment
Burks, W., Laubach, S., Jones, S. Journal of Allergy and Clinical Immunology 2008;121 (6):1299.

Mucosal immunization application to allergic disease: Sublingual immunotherapy
Frati, F., Moingeon, P., Marcucci, F., Puccinelli, P., Sensi, L., Di Cara, G., Incorvaia, C. Allergy and Asthma Proceedings 2007; 28 (1): 35-39(5).

Key Points:

  • There are two primary mechanisms for inducing oral tolerance: active suppression by regulatory T cells clonal anergy or deletion.
  • The primary factor that determines clonal anergy or deletion is the dose of antigen.
  • Low doses of antigen favor tolerance driven by regulatory cells.


Update on sublingual immunotherapy
Potter, MD, FCP(SA), DCH(SA) Annals of Allergy, Asthma & Immunology 2006; 96(2): S22-25.

Key Points:

  • Long-lasting tolerance is achieved after two to four years of SLIT, typically in patients with persistent perennial nasal allergies and also those with asthma.