Background: A major problem of venom-specific immunotherapy (VIT) is the absence of reliable parameters for deciding treatment discontinuation. Aim of the Study: Intracutaneous tests (ICTs), the basophil activation test (BAT), specific IgEs (sIgEs) and blocking factor (BF) activity were measured during VIT. We made an evaluation by means of a protective index (PI) including ICT, BAT and BF values. Material and Methods: A population of 45 patients who had experienced a systemic reaction after an insect sting were tested before VIT (T0), at 1 week (T1w), at 10 weeks (T10w) and at 21 weeks (T21w), and, for a subgroup of 17 patients, at 3-5 years (T3-5y). Basophil activation (expressed in % CD63 and in the area under the curve) and BF activity were measured by flow cytometry using the CCR3/CD63 protocol. Results: The first 21 weeks of follow-up showed no significant variation in the ICT, sIgE and BAT measurements, except for BAT, by eliminating weak negative anti-IgE responses. In these conditions, the decrease in basophil activation was significant at T10w (p = 0.009) and T21w (p = 0.009). Increased BF activity was also significant at T10w (p = 0.008) and T21w (p = 0.002). The PI threshold calculated from the mean ± 3 standard errors (SE) was 64.8 (14.7 ± 16.7, n = 25) at T0. PI increase was significant at T3-5y (3,430 ± 6,282; p < 0.001). Conclusion: VIT induced a significant decrease in ICT values and basophil activation, along with an increase in serum BF activity, significant after 10 weeks of VIT. Evaluated in a larger population, the PI could represent a new tool for the clinico-biological follow-up of VIT efficacy.

Karasuyama H, Obata K, Wada T, Tsujimura Y, Mukai K: Newly appreciated roles for basophils in allergy and protective immunity. Allergy 2011;66:1133-1141.
Ebo DG, Sainte-Laudy J, Bridts CH, Mertens CH, Hagendorens MM, Schuerwegh AJ, De Clerck LS, Stevens WJ: Flow-assisted allergy diagnosis. Current applications and future perspectives. Allergy 2006;61:1028-1039.
Hoffmann HJ: News in cellular allergology: a review of the human mast cell and basophil granulocyte literature from January 2013 to May 2015. Int Arch Allergy Immunol 2015;168:253-262.
Homšak M, Šilar M, Berce V, Tomazin M, Skerbinjek-Kavalar M, Čelesnik N, Košnik M, Korošec P: The relevance of basophil allergen sensitivity testing to distinguish between severe and mild peanut-allergic children. Int Arch Allergy Immunol 2013;162:310-317.
Ebo DG, Hagendorens MM, Schuerwegh AJ, Beirens LM, Bridts CH, De Clerck LS, Stevens WJ: Flow-assisted quantification of in vitro activated basophils in the diagnosis of wasp venom allergy and follow-up of wasp venom immunotherapy. Cytometry B Clin Cytom 2007;72:196-203.
Kucera P, Cvackova M, Hulikova K, Juzova O, Pachl J: Basophil activation can predict clinical sensitivity in patients after venom immunotherapy. J Invest Allergol Clin Immunol 2010;20:110-116.
Korošec P, Šilar M, Eržen R, Čelesnik N, Bajrović N, Zidarn M, Košnik M: Clinical routine utility of basophil activation testing for diagnosis of hymenoptera-allergic patients with emphasis on individuals with negative venom-specific IgE antibodies. Int Arch Allergy Immunol 2013;161:363-368.
Chirumbolo S: Basophil activation test in allergy: time for an update? Int Arch Allergy Immunol 2012;158:99-114.
Jutel M, Muller UR, Fricker M, Rihs S, Pichler WJ, Dahinden C: Influence of bee venom immunotherapy on degranulation and leukotriene generation in human blood basophils. Clin Exp Allergy 1996;26:1112-1118.
Read S, Powrie F: CD4+ regulatory T cells. Curr Opin Immunol 2001;13:644-649.
Jutel M, Akdis M, Blaser K, Akdis CA: Are regulatory T cells the target of venom immunotherapy? Curr Opin Allergy Clin Immunol 2005;5:365-369.
Till SJ, Francis JN, Nouri-Aria K, Durham SR: Mechanism of immunotherapy. J Allergy Clin Immunol 2004;113:1025-1034.
Lerch E, Muller UR: Long-term protection after stopping venom immunotherapy: results of re-stings in 200 patients. J Allergy Clin Immunol 1998;101:606-612.
Bilo BM, Bonifazi F: Hymenoptera venom immunotherapy. Immunotherapy 2011;3: 229-246.
Reisman RE, Lantner R: Further observations of stopping venom immunotherapy: comparison of patients stopped because of a fall in serum venom-specific IgE to insignificant levels with patients stopped by self-choice. L Allergy Clin Immunol 1989;83:1049-1054.
Muller U, Helbling A, Bischof M: Predictive value of venom-specific IgE, IgG and IgG subclass antibodies in patients on immunotherapy with honey bee venom. Allergy 1989;44:412-418.
Scadding GW, Shamji MH, Jacobson MR, et al: Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells. Clin Exp Allergy 2010;40:598-606.
Jones SM, Pons L, Roberts JL, et al: Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol 2009;124:292-300.
Wutrich B, Arrendal H, Lanner A: Allerqie aux piqures d'hym6noptères. Différents types de réactions immunologiques pendant l'immunothérapie avec les venins. Rev Fr Allergol Immunol Clin 1982;22:199-205.
Lichtenstein LM, Valentine MD, Sobotka AK: A case for venom treatment in anaphylactic sensitivity to Hymenoptera sting. N Engl J Med 1974;290:1223-1227.
Eberlein-Konig B, Ullmann S, Thomas P, Przybilla B: Tryptase and histamine release due to a sting challenge in bee venom allergic patients treated successfully or unsuccessfully with hyposensitization. Clin Exp Allergy 1995;25:704-712.
Peternelj A, Silar M, Erzen R, Kosnik M, Korosec P: Basophil sensitivity in patients not responding to venom immunotherapy. Int Arch Allergy Immunol 2008;146:248-254.
Gober LM, Eckman JA, Sterba PM, et al: Expression of activation markers on basophils in a controlled model of anaphylaxis. J Allergy Clin Immunol 2007;119:181-188.
Maunsell K: Direct test for blocking antibody in treated hay-fever. Lancet 1946;2:199-201.
Kanny G, Croizier A, Ragazzini JP, Moneret-Vautrin DA: Suivi immunologique des désensibilisations aux venins d'hyménoptères. Intérêt du test de Maunsell. Rev Fr Allergol 1993;33:274-283.
Sainte-Laudy J, Touraine F, Cluzan D, Belle Moudourou F: Application de la cytométrie en flux au diagnostic de l'hypersensibilité IgE dépendante induite par les venins d'hymenoptères. Comparaison des résultats observés pour les réactions systémiques et les réactions locales ou locorégionales. Rev Fr Allergol 2013;53:450-457.
Sainte-Laudy J, Touraine F: Use of basophil sensitivity not reactivity as a good marker for allergy diagnosis. Inflamm Res 2009;58:S28-S29.
Patil SU, Shreffler WG: Immunology in the clinic review series; focus on allergies: basophils as biomarkers for assessing immune modulation. Clin Exp Immunol 2011;167:59-66.
Erdmann SM, Sachs B, Kwiecien R, Moll-Slodowy S, Sauer I, Merk HF: The basophil activation test in wasp venom allergy: sensitivity, specificity and monitoring specific immunotherapy. Allergy 2004;59:1102-1109.
Novak J, Mete N, Bussmann C, Maintz L, Bieber T, Akdis M, et al: Early suppression of basophil activation during allergen specific immunotherapy by histamine receptors 2. J Allergy Clin Immunol 2012;130:1153-1158.
Haye R, Dosen LK: Insect sting allergy. A study from 1980 to 2003 of patients who started treatment with venom immunotherapy between 1980 and 1998. Clin Mol Allergy 2005;3:12-20.
Siegmund R, Vogelsang H, Machnik A, Herrmann D: Surface membrane antigen alteration on blood basophils in patients with Hymenoptera venom allergy under immunotherapy. J Allergy Clin Immunol 2000;106:1190-1195.
Mikkelsen S, Bibby BM, Dolberg MK, Dahl R, Hoffmann HJ: Basophil sensitivity through CD63 or CD203c is a functional measure for specific immunotherapy. Clin Mol Allergy 2010;8:2-9.
Malveaux FJ, Conroy MC, Adkinson NF Jr, Lichtenstein LM: IgE receptors on human basophils. Relationship to serum IgE concentration. J Clin Invest 1978;62:176-181.
Ejrnaes AM, Svenson M, Lund G, Larsen JN, Jacobi H: Inhibition of rBet v 1-induced basophil histamine release with specific immunotherapy-induced serum immunoglobulin G: no evidence that Fcgamma RIIB signalling is important. Clin Exp Allergy 2006;36:273-282.
Sainte-Laudy J, Ouk C: Use of lipid rafting for the analysis of human basophil activation by flow cytometry. Inflamm Res 2010;59:S193-S115.
Plewako H, Wosinska K, Arvidsson M, et al: Basophil interleukin 4 and interleukin 13 production is suppressed during the early phase of rush immunotherapy. Int Arch Allergy Immunol 2006;141:346-353.
Cady CT, Powell MS, Harbeck RJ et al: IgG antibodies produced during subcutaneous allergen immunotherapy mediate inhibition of basophil activation via a mechanism involving both FcgammaRIIA and FcgammaRIIB. Immunol Lett 2010;130:57-65.
Daeron M, Malbec O, Arock M, Fridman WH: Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors. J Clin Invest 1995;95:577-585.
Kepley CL, Cambier JC, Morel PA, et al: Negative regulation of FcepsilonRI signaling by FcgammaRII costimulation in human blood basophils. J Allergy Clin Immunol 2000;106:337-348.
Golden DBK, Kwiterovich KA, Kagey-Sobotka A, Lichtenstein LM: Discontinuing venom immunotherapy: extended observations. J Allergy Clin Immunol 1998;101:298-305.
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