Table of Contents

m218 Asp f 1 Scientific Information Summary Epidemiology Environmental Characteristics Clinical Relevance Molecular Aspects Diagnostic Relevance Compiled By

Component

m218 Asp f 1

m218 Asp f 1 Scientific Information

Type:

Component

Name; WHO/IUIS:

Asp f 1

Biological function:

unknown

Allergen code:

m218

Molecular Weight:

18 kDa

Source Material:

Recombinant, CCD-free protein

Other Names :

Ribonuclease mitogillin

Summary

Asp f 1, the ribonuclease mitogillin, a member of the ribotoxin family, is a major allergen of and marker of genuine sensitization to the ubiquitous environmental mold Aspergillus fumigatus (A. fumigatus), associated to allergic fungal airway diseases (AFAD) affecting upper and lower airways, such as allergic fungal rhinosinusitis (AFRS), severe asthma with fungal sensitization (SAFS), and allergic bronchopulmonary aspergillosis (ABPA). Asp f 1, a secreted protein, exerts cytotoxic and proinflammatory effects.

Epidemiology

Worldwide distribution

A. fumigatus is a cosmopolitan, thermotolerant airborne fungus affecting human health through multiple pathways: sensitization and allergy, infection, direct toxicity [1].

The prevalence of Asp f 1 sensitization is highly variable depending on the study population in terms of geography, underlying lung condition (asthma, CF, or COPD), stage of AFAD, method of assessment (skin prick test, blood tests) and cut-off values (reviewed in [2, 3]). Despite wide variations, Asp f 1 sensitization presents with higher prevalence and higher levels in ABPA as compared to control populations. For example, Asp f 1 sensitization in ABPA was found at 60% and 67% in two Japanese cohorts [4, 5], at 83% in British patients [6] and at 100% in French patients [7]. In asthmatic patients with A. fumigatus sensitization, detectable IgE to Asp f 1 was reported in 18% of Japanese patients [4] and in 46% of German and Polish patients [8].

In an unselected population of 23,077 consecutive Italian subjects with a suspicion of airborne or food allergy, 0.43% displayed detectable IgE sensitization to Asp f 1, ranking 64 among 75 assayed allergenic molecules, and in 10% Asp f 1 presented as apparent monosensitization [9]

Environmental Characteristics

Source and tissue

Asp f 1 is a secreted ribonuclease [10].

Risk factors

Sensitization and allergy to A. fumigatus occur mainly in subjects with pre-existent lung conditions, usually asthma or cystic fibrosis (CF), although chronic obstructive pulmonary disease (COPD) is increasingly recognized as another predisposing condition [1].

Clinical Relevance

Detailed information regarding A. fumigatus is available in the whole allergen section. The demonstration of Asp f 1 IgE confirms genuine sensitization to A. fumigatus [10].

Clinical relevance of Asp f 1 IgE in ABPA

The diagnosis of ABPA is often complicated by symptoms due to underlying conditions and a complex pathophysiology combining IgE and IgG responses, sputum and systemic eosinophilia, and much debated fungal colonization [3, 11]. The levels, rather than the prevalence, of Asp f 1 sensitization have been proposed as a diagnostic criterion for ABPA [2, 7, 12]. Median levels of IgE to Asp f 1 in ABPA patients may vary from 2.5 kUA/L to 17 kUA/L among different cohorts [5-7, 12], supporting the observation that statistically determined cut-off levels in a given population perform better than fixed cut-offs [12]. Using population-based cut-offs, the reported area under the receiver operating curve of Asp f 1 was close to 0.9 in different populations [7, 12]. A meta-analysis showed a pooled sensitivity of 80% and pooled specificity of 70.1% for Asp f 1 as a diagnostic tool for ABPA in asthmatic patients, and 78.9% and 81.9% respectively for the diagnosis of ABPA in CF patients [2]. Diagnostic performance of Asp f 1 is improved when used in conjunction with other A. fumigatus molecular allergens [12-14] .

Disease severity and prediction

Increasing levels of Asp f 1 IgE in asthmatic or CF patients are statistically associated to an increased risk of ABPA, as explained above. Outside ABPA, it has long been known that sensitization to A. fumigatus is associated with lung function deterioration in adult and pediatric asthmatic patients [15, 16]. Using molecular allergen diagnostics in a COPD cohort, it was shown that Asp f 1 sensitization, rather than A. fumigatus sensitization, was associated with bronchiectasis, an irreversible complication leading to poorer lung function and mortality [17]. In this study, Asp f 1 sensitization was detectable in 12% of COPD patients and in 2% of controls (p = 0.02) and was associated with an odds ratio of 2.8 for having bronchiectasis.

Cross-reactive molecules

Asp f 1 is a member of the ribotoxin family and shares a sequence identity of 80% or with homologues from a small number of other Aspergillus species, mainly restrictocin from A. restrictus, and α-sarcin from A. giganteus [18-20].

Molecular Aspects

Biochemistry

Asp f 1 is a basic protein of 18 kDa, stabilized by four disulfide bonds, secreted by A. fumigatus into the environment. Similar to other members of the ribotoxin family, it acts as a ribonuclease. Asp f 1 targets the ribosome and thus blocks protein synthesis. Its biological function, although not yet identified, might relate to fungal defense and parasitism [19, 20]. The presentation of Asp f 1 is restricted to HLA DR2 and DR5 [21].

Isoforms, epitopes, antibodies

As of November 7th, 2021, Asp f 1 comprises only one isoallergen officially published by the World Health Organization (WHO) and the International Union of Immunological Societies (IUIS) Allergen Nomenclature: Asp f1.0101 [22].

Cross-reactivity due to structural similarity

Asp f 1 cross-reactivity at the IgE binding level has been reported with ribotoxins from a limited number of other Aspergillus species [18, 20].

Diagnostic Relevance

Disease Severity

Asp f 1 sensitization, a marker of genuine sensitization to A. fumigatus, is associated with ABPA [2]and lung function deterioration in COPD patients [17]

Cross-Reactivity

Asp f 1 displays clinically relevant cross-reactivity with a small number of related allergens from other Aspergillus species.

Exposure

Asp f 1 sensitization is believed to occur mainly through inhalation upon exposure to A. fumigatus [10]

Compiled By

Author: Joana Vitte

Reviewer: Dr. Christian Fischer

Last reviewed:January 2022

References

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