Early Cytokine Modulation after the Rapid Induction Phase of Sublingual Immunotherapy with Mite Monomeric Allergoids

Gioacchino, Mario Di; Perrone, A.; Petrarca, Claudia; Claudio, F.; Mistrello, G.; Falagiani, P.; Dadorante, V; Verna, N; Braga, M.; Ballone, Enzo; Cavallucci, E.

doi:10.1177/039463200802100421

Cited by 17 publications

(22 citation statements)

References 28 publications

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“…However, in our trial, the modulation of IL-l°did not occur; this finding could be due to the timing chosen for cytokine determination. In fact, the increase in IL-I0 has been observed in short-term studies of 2-6 months (13,18,20,21), whereas our laboratory assessments were carried out after one year of treatment. The timing in detecting such immunological change is of crucial importance.…”

Section: Discussionmentioning

confidence: 94%

Dose-Dependent Clinical and Immunological Efficacy of Sublingual Immunotherapy with Mite Monomeric Allergoid

Gioacchino

Cavallucci

Ballone

et al. 2012

Int J Immunopathol Pharmacol

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Sublingual immunotherapy with monomeric carbamylated allergoid (LAIS) is an effective and well tolerated treatment of respiratory allergy. The aim of the present study was to correlate the efficacy of two maintenance doses (1000 AU vs 3000 AU) of LAIS with the immunological modulation of allergendriven Thl, Th2 and T regulatory cytokines produced in vitro by PBMCs, in patients suffering from mite allergic rhinitis. Forty-eight consecutive patients with mite allergic rhinitis were recruited. Patients were randomly assigned to group A (n=24) or group B (n=24), respectively receiving 1000 AU or 3000 AU weekly during one-year maintenance phase. Each patient was evaluated for rhinitis severity (ARIA protocol), and for drug consumption at the time ofthe inclusion and after 6 and 12 months oftreatment. Patients were also asked to report the perceived severity of the disease and the tolerability of the treatment in a visual analogical scale (VAS). Before and at the end of the treatment allergen-driven release of cytokines by PBMCs in vitro was measured. After J-year treatment, a statistically significant reduction of all clinical parameters was observed in all patients, associated with reduction of IL-4 and increase of INF-y secreted in vitro by mite-challenged PBMCs. Notably, the group treated with the higher dose showed significantly better clinical and immunological results. The efficacy of LAIS is correlated to the immune modulation in a clear dose-dependent effect.Sublingual specific immunotherapy with monomeric carbamylated allergoid (LAlS) is an effective and well tolerated treatment of respiratory allergy (1-5). The monomeric allergoid was obtained by carbamylation of the allergen with potassium cyanate at alkaline pH, a reaction that leads to a substantial substitution of the s-amino groups of the lysine residues within the protein. This simple chemical modification confers to the allergoid a series ofcharacteristics (6) which made it particularly appropriate for sublingual administration. Among them,thehypoallergenicity andthemonomericity, that

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Section: Discussionmentioning

confidence: 94%

Dose-Dependent Clinical and Immunological Efficacy of Sublingual Immunotherapy with Mite Monomeric Allergoid

Gioacchino

Cavallucci

Ballone

et al. 2012

Int J Immunopathol Pharmacol

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“…Also, recent scientific interest has been focused on eliciting regulatory T cells (Treg) capable of downregulating both Th1 and Th2 responses through the production of interleukin (IL)-10 and/or transforming growth factor (TGF)-β [14,15,16,17]. Furthermore, preliminary clinical studies on SLIT indicated a similar early Treg-related interleukin production with consequent downmodulation of the immune response [18,19,20]. Although there have been several important studies published, most have been associated with particularly long periods of treatment.…”

Section: Introductionmentioning

confidence: 99%

Sublingual Allergen-Specific Immunotherapy Adjuvanted with Monophosphoryl Lipid A: A Phase I/IIa Study

Pfaar

Barth

Jaschke

et al. 2010

Int Arch Allergy Immunol

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Background: Sublingual immunotherapy (SLIT) allergy vaccines have an excellent safety profile, but opinions vary on their efficacy, and treatment regimens are often lengthy. This study assessed the effects of the Toll-like receptor 4 agonist monophosphoryl lipid A (MPL®) on safety/tolerability and clinical and immunological efficacy when combined with grass pollen SLIT formulations in treating patients with seasonal allergic rhinitis. This is the first reported study of adjuvanted SLIT. Methods: In this double-blind placebo-controlled phase I/IIa study, 80 grass pollen-sensitive subjects were randomized into 4 groups of 20 subjects to receive daily treatment for 8 weeks. Sixteen patients per group received SLIT and 4 received placebo. The formulation given to each group varied with respect to grass pollen extract and MPL content. Grass allergen nasal challenge tests (NCTs) were performed prior to dosing and in weeks 4 and 10. Grass pollen-specific immunoglobulin G (IgG) and IgE antibodies were measured at baseline and prior to dosing in weeks 2, 3, 4, 5 and 10. Results: Local and systemic adverse events were generally comparable for patients who received active treatment and placebo. Patients in the 2 groups given SLIT containing the highest amount of MPL experienced the highest proportion of negative NCTs after 10 weeks (47 and 44%, vs. 20% with placebo). These patients also showed earlier median increases in specific IgG and smaller increases in IgE levels than those receiving other formulations. Conclusions: These results suggest that SLIT preparations containing MPL are well tolerated and alter the immunological response to grass antigens after 3 weeks of exposure, with an associated suppression of nasal challenge responses.

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“…This seems to be related to the favorable cytokine changes (allergen-specific activation of IL-10 secreting Treg lymphocytes) shown in previous studies with the same immunotherapy (mite allergoid SLIT) (15).…”

Section: Discussionmentioning

confidence: 54%

“…A timeresponse effect was observed by Di Gioacchino et al in an immunological study comparing the effects on IL-IO and other cytokines (INF-y, IL-4, IL-6, IL-2, TNF-a) of two different SLIT induction schemes, one lasting 14 weeks and the other 16 days. The faster administration, with patients taking the tablets at shorter intervals, was associated with greater changes in these parameters, regardless of the total amount of allergen administered (15).…”

Section: Discussionmentioning

confidence: 91%

Sublingual Allergoid Immunotherapy: A New 4-Day Induction Phase in Patients Allergic to House Dust Mites

D'Anneo

Bruno

Falagiani

2010

Int J Immunopathol Pharmacol

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Sublingual immunotherapy with monomeric allergoid (allergoid SLIT), given according to the standard scheme, has proved effective and safe in many clinical trials. However, its build-up phase requires a long time ranging from 16 days to 14 weeks. This study therefore investigated whether, with a four-day up-dosing, the same benefit could be achieved in a shorter time. Thirty rhinitic and/or asthmatic patients (16 M and 14 F, mean age 36±8.2 years) allergic to house dust mites (HDM) with or without other sensitizations were randomized to allergoid SLIT or standard drug therapy. The build-up phase lasted four days. The first day the patients took a 300 AU tablet, the second day two 300 AU tablets, the third day three 300 AU tablets and the fourth day four 300 AU tablets. The total amount taken during the up-dosing was 3000 AU. Patients were then treated for 12 months at the dosage of 2000 AU/week (total amount of allergen: 104,000 AU/year). The symptom score and drug consumption were recorded from November to February on monthly diary cards. At baseline and after 12 months a Visual Analogue Scale (VAS) was used to rate the patients' well-being. Skin prick test reactivity was evaluated before and after the 12-month treatment in both groups using 10 mg/mL histamine as reference. VAS scores rose significantly (about 45%) in both groups in comparison to baseline (p=0.001). In addition, there was a significantly greater reduction of the global symptoms score (about 52%) - but not in drug consumption - in the SLIT group in comparison to controls (p=0.0004). The SLIT group showed a highly significant reduction (about 39%) in skin prick test reactivity (p=0.000003) while the control group remained unchanged (p=0.5226). No severe adverse events were observed. Even with this short four-day up-dosing, the allergoid SLIT proves to be safe. In addition, it is already effective in patients allergic to HDM after 12 months, and significantly reduces allergen-specific skin reactivity.

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Early Cytokine Modulation after the Rapid Induction Phase of Sublingual Immunotherapy with Mite Monomeric Allergoids

Cited by 17 publications

References 28 publications

Dose-Dependent Clinical and Immunological Efficacy of Sublingual Immunotherapy with Mite Monomeric Allergoid

Dose-Dependent Clinical and Immunological Efficacy of Sublingual Immunotherapy with Mite Monomeric Allergoid

Sublingual Allergen-Specific Immunotherapy Adjuvanted with Monophosphoryl Lipid A: A Phase I/IIa Study

Sublingual Allergoid Immunotherapy: A New 4-Day Induction Phase in Patients Allergic to House Dust Mites

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