Buscar en
Allergologia et Immunopathologia
Toda la web
Inicio Allergologia et Immunopathologia The future of immunotherapy with individual allergens: Immunotherapy with fungi
Journal Information
Vol. 45. Issue S1.
Sagunto's Second Scientific Meeting on Immunotherapy. Regulation and Current Situation.
Pages 36-38 (December 2017)
Share
Share
Download PDF
More article options
Vol. 45. Issue S1.
Sagunto's Second Scientific Meeting on Immunotherapy. Regulation and Current Situation.
Pages 36-38 (December 2017)
Review
Full text access
The future of immunotherapy with individual allergens: Immunotherapy with fungi
Visits
1053
F. Pineda
Diater Laboratorios, Madrid, Spain
This item has received
Article information
Full Text
Bibliography
Download PDF
Statistics
Figures (1)
Tables (1)
Table 1. Results for the primary endpoint (combined index of symptoms and medication) and secondary endpoints (skin reactivity and IgG4).
Full Text

Exposure to fungi has two main features: in addition to its allergenicity, it is a major risk factor for individuals with a predisposition to allergic disease. Exposure remains predominantly external but there are increasing references to indoor exposures.1–5 The prevalence of sensitivity to these sources of sensitization is not clear. The dispersion of data due to the use of extracts with different allergenic profiles,6 caused by different levels of expression of the strain selected,7–10 the conditions and characteristics of cultivation and growth, and the selection of the most appropriate protocol for the extraction of the proteins expressed, result in wide variability in epidemiological data.11–19

There are an estimated 1–1.5 million fungal species worldwide, of which around 80,000 have been described: only 112 are considered allergenic sources.20 The four genera most commonly associated with allergic disease are Alternaria,21Cladosporium, Penicillium and Aspergillus. A total of 107 allergens from 28 fungal genera have been accepted by the International Union of Immunological Societies (IUIS) subcommittee that lists allergens internationally, and form part of its database.

Fungi are known to produce a wide range of reactive IgE responses, and the factor that determines this variability is the recognition of the proteins that constitute an allergenic source. The definition of major allergen (one that originates specific IgE responses in more than 50% of patients sensitized to the allergen)22 has a local connotation and its binding capacity with the IgE from a specific allergic patient does not always reflect its clinical relevance. In the case of the genus Alternaria and, specifically, Alternaria alternata species, the major allergen Alt a 1 is recognized by more than 90% of individuals sensitized to this source globally and by a large percentage of asthmatic patients. Alt a 1 is present in more than 50 phylogenetically-related species,20,23 and may be considered as the allergen that best defines the diagnosis of allergy to fungi in our setting, and as a replacement for the complex and heterogeneous extract of Alternaria alternata as a diagnostic and therapeutic tool in respiratory allergy caused by fungi.

The International Council for the harmonization of technical requirements for medicinal products for human use (ICH) proposes the use of a guideline or common technical document (CTD)24 in order to achieve greater equality in the technical characteristics of candidate drugs for marketing authorization to ensure the safety and efficacy of the product used in the diagnosis and treatment of allergic patients.

In this sense, the technical characteristics of the major allergen Alt a 1 purified from an extract of Alternaria alternata are ordered according to the recommendations of the aforementioned guide and based on the criteria recommended in it.

The chapter on technical criteria is based on the description of the process of obtaining the active substance (purified Alt a 1) by validated chromatographic methods, the subsequent analysis of the physicochemical and immunological characteristics of the substance, and the configuration of the final product based on criteria of biological activity, stability and sterility, and on the absence of toxic and irritating elements, in addition to those already mentioned in the chapter on the active substance.

The biological activity of Alt a 1 was evaluated according to the Nordic guidelines, and applying their methodology and criteria. This showed that 1 HEP (10,000UB/mL) corresponded to 5.97g/mL of Alt a 1, with a 95% confidence interval ranging from 1.71 to 7.16μg/mL.

Safety and efficacy trials25 were made using a randomized, double-blind, placebo-controlled design in patients with allergic rhinitis with or without mild-to-moderate asthma, as indicated by the EMA guidelines on immunotherapy with allergenic extracts. Significant increases in immunogenicity and reductions in the combined symptoms/medication index and cutaneous reactivity.

The most effective and safest dose was 0.36mg of Alt a 1 given monthly for two years.

Fig. 1 shows the segregation by groups and the different stages of the trial and Table 1 the results obtained.

Figure 1.

Segregation by groups and stages of the trial.

(0.14MB).
Table 1.

Results for the primary endpoint (combined index of symptoms and medication) and secondary endpoints (skin reactivity and IgG4).

Conflict of interest

The author reports being employed by Diater Laboratories, a pharmaceutical company specializing in the production of allergenic extracts for in vivo diagnosis and treatment of allergies.

No other potential conflict of interest relevant to this letter was reported.

References
[1]
Suzanne Gravesen, Peter A. Nielsen, Randi lversen, Kristian Fog Nielsen.
Microfungal contamination of damp buildings-examples of risk constructions and risk materials.
Environ Health Perspect, 107 (1999), pp. 505-508
[2]
Abba I. Terr.
Are indoor molds causing a new disease?.
J Allergy Clin Immunol, 113 (2004), pp. 221-226
[3]
E.D. Hamilton.
Pollen and fungus spore counts.
Proc R Soc Med, 56 (1963), pp. 220-221
[4]
J. Lacey.
Spore dispersal – its role in ecology and disease: the British contribution to fungal aerobiology.
Mycol Res, 100 (1996), pp. 641-660
[5]
S.Y. Oh, J.J. Fong, M.S. Park, L. Chang, Y.W. Lim.
Identifying airborne fungi in Seoul, Korea using metagenomics.
J Microbiol, 52 (2014), pp. 465-472
[6]
Robert E. Esch.
Manufacturing and standardizing fungal allergen products.
Allergy Clin Immunol, 113 (2004), pp. 210-215
[7]
T.E. Twaroch, M. Focke, K. Fleischmann, N. Balic, C. Lupinek, K. Blatt, et al.
Carrier-bound Alt a 1 peptides without allergenic activity for vaccination against Alternaria alternata allergy.
Clin Exp Allergy, 42 (2012), pp. 966-975
[8]
Teresa E. Twaroch, Mirela Curin, Rudolf Valenta, Ines Swoboda.
Mold allergens in respiratory allergy: from structure to therapy.
Allergy Asthma Immunol Res, 7 (2015), pp. 205-220
[9]
J. Martínez, A. Gutiérrez, I. Postigo, G. Cardona, J. Guisantes.
Variability of Alt a 1 expression by different strains of Alternaria alternata.
J Investig Allergol Clin Immunol, 16 (2006), pp. 279-282
[10]
M. Sáenz-de-Santamaría, J.A. Guisantes, J. Martínez.
Enzymatic activities of Alternaria alternata allergenic extracts and its major allergen (Alt a 1).
[11]
G. D’Amato, F.T. Spieksma.
Aerobiologic and clinical aspects of mould allergy in Europe.
Allergy, 50 (1995), pp. 870-877
[12]
Renato Corsico, Barbara Cinti, Vincenzo Feliziani, Maria Teresa Gallesio, Gennaro Liccardi, Anna Loreti, et al.
Prevalence of sensitization to Alternaria in allergic patients in Italy.
Ann Allergy Asthma Immunol, 80 (1998), pp. 71-76
[13]
M. Wiszniewska, D. Tymoszuk, E. Nowakowska-Świrta, C. Pałczyński, J. Walusiak-Skorupa.
Mould sensitisation among bakers and farmers with work-related respiratory symptoms.
Ind Health, 51 (2013), pp. 275-284
[14]
G. D’Amato, G. Chatzigeorgiou, R. Corsico, D. Gioulekas, L. Jäger, S. Jäger, et al.
Evaluation of the prevalence of skin prick test positivity to Alternaria and Cladosporium in patients with suspected respiratory allergy. A European multicenter study promoted by the Subcommittee on Aerobiology and Environmental Aspects of Inhalant Allergens of the European Academy of Allergology and Clinical Immunology.
Allergy, 52 (1997), pp. 711-716
[15]
S.J. Arbes Jr., P.J. Gergen, L. Elliott, D.C. Zeldin.
Prevalences of positive skin test responses to 10 common allergens in the US population: results from the third National Health and Nutrition Examination Survey.
J Allergy Clin Immunol, 116 (2005), pp. 377-383
[16]
J. Bartra, J. Belmonte, J.M. Torres-Rodriguez, A. Cistero-Bahima.
Sensitization to Alternaria in patients with respiratory allergy.
Front Biosci (Landmark Ed), 14 (2009), pp. 3372-3379
[17]
A. Cantani, V. Ciaschi.
Epidemiology of Alternaria alternata allergy: a prospective study in 6840 Italian asthmatic children.
Eur Rev Med Pharmacol Sci, 8 (2004), pp. 289-294
[18]
G. Loureiro, M.A. Rabaçaa, B. Blancoa, S. Andradea, C. Chieiraa, C. Pereira.
Aeroallergens sensitization in an allergic paediatric population of Cova da Beira, Portugal.
Allergol Immunopathol, 33 (2005), pp. 192-198
[19]
L. Heinzerling, A.J. Frew, C. Bindslev-Jensen, S. Bonini, J. Bousquet, M. Bresciani, et al.
Standard skin prick testing and sensitization to inhalant allergens across Europe – a survey from the GA2LEN network.
[20]
B. Simon-Nobbe, U. Denk, V. Pöll, R. Rid, M. Breitenbach.
The spectrum of fungal allergy.
Int Arch Allergy Immunol, 145 (2008), pp. 58-86
[21]
A. Mari, P. Schneider, V. Wally, M. Breitenbach, B. Simon-Nobbe.
Sensitization to fungi: epidemiology, comparative skin tests, and IgE reactivity of fungal extracts.
Clin Exp Allergy, 33 (2003), pp. 1429-1438
[22]
H. Lowenstein, T.P. King, L. Goodfriend, R. Hussain, M. Roebber, D.G. Marsh.
Antigens of Ambrosia elatior (short ragweed) pollen. II. Immunochemical identification of known antigens by quantitative immunoelectrophoresis.
J Immunol, 127 (1981), pp. 637-642
[23]
Antonio Moreno, Fernando Pineda, Javier Alcover, David Rodríguez, Ricardo Palacios, Eduardo Martínez-Naves, et al.
Diagnostic Utility of Major Allergen Alt a 1.
Allergy Asthma Immunol Res, 8 (2016), pp. 428-437
[24]
European Medicines Agency.
ICH Topic M4. Common technical document for the registration of pharmaceuticals for human use organization CTD. February.
(2004),
CPMP/ICH/2887/99
[25]
Luis Prieto, Ricardo Palacios, Dulce Aldana, Anna Ferrer, Carmen Perez-Frances, Victoria Lopez, et al.
Effect of allergen-specific immunotherapy with purified Alt a1 on AMP responsiveness, exhaled nitric oxide and exhaled breath condensate pH: a randomized double blind study.
Allergy Asthma Clin Immunol, 6 (2010), pp. 27
Copyright © 2017. SEICAP
Article options
Tools
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos

Quizás le interese:
10.1016/j.aller.2018.10.002
No mostrar más