w230 Amb a 1

Amb a 1 is a pectate lyase from short ragweed (Ambrosia artemisiifolia) pollen. Amb a 1 is a marker of sensitization to ragweed pollen. It displays limited cross-reactivity mainly within the Asteraceae pollen, with pectate lyase Art v 6 from mugwort (Artemisia vulgaris) and Hel a 6 from sunflower pollen.

Worldwide distribution

Ambrosia sp pollen is a frequent and increasing cause of weed pollinosis in Europe, North America, and China  [1, 2]. Ragweed sensitization is reported in up to 45% of North American atopic subjects [3]. Among the twelve A. artemisiifolia (short ragweed) allergens present in the IUIS/WHO database [4], Amb a 1 is a major allergen and a marker of sensitization to Ambrosia sp pollen [1].

Amb a 1 sensitization is observed in 95% - 97% of ragweed-allergic patients [1, 5]. In areas with high exposure to both Ambrosia sp and Artemisia sp (mugwort), the prevalence of Amb a 1 sensitization may be unrelated to the prevalence of sensitization to the corresponding pollen extract, because of primary sensitization to Artemisia and cross-reactivity between the whole allergen extracts [1].

In areas with low exposure to ragweed pollen, the prevalence of Amb a 1 sensitization is low, even among physician-diagnosed patients with allergic rhinitis (AR), as demonstrated in German and Czech studies [6, 7].

Source and tissue

Amb a 1, previously known as ragweed antigens E and K [3], was demonstrated as the dominant major allergen of A. artemisiifolia as early as 1978 [5].

Amb a 1 is present in A. artemisiifolia pollen and sub-pollen allergenic particles [8, 9]. It is mostly found in the PM10 atmospheric particles [8].

Risk factors

The main risk factor for developing sensitization to Amb a 1 is exposure to A. artemisiifolia pollen [1]. Climate and pollution affect Amb a 1 concentrations and allergenicity through multiple mechanisms, e.g. increased amounts of Amb a 1 in pollen from A. artemisiifolia growing under high levels of CO2, increased allergenicity of Amb a 1 due to the loss of IgE-binding modulators in pollen from A. artemisiifolia grown at high temperature, and increased allergenicity of ragweed pollen exposed to traffic pollution [10, 11].

In areas of high exposure to Artemisia vulgaris pollen, it has been suggested that Amb a 1 sensitization might result from primary Art v 6 sensitization, but the question is still debated [12].

Detailed information regarding A. artemisiifolia pollinosis, which manifests itself mainly as allergic rhinitis, rhinoconjunctivitis and asthma, is available in the whole allergen section. 

Disease severity and prediction

In patients with a case history evocative of Ambrosia sp pollinosis and sensitization to Ambrosia whole allergen extract, the demonstration of Amb a 1 IgE confirms sensitization to this pollen [1]. 

 Cross-reactive molecules

Amb a 1 cross-reactivity is mainly observed within the pectate lyase family. Cross-reactivity has been reported with homologues from other Ambrosia species [1], such as Art v 6, a minor allergen of Artemisia vulgaris [13] and Hel a 6 [14], a major allergen of Helianthus annuus (sunflower) pollen [14]. Amb a 1 also shows a degree of cross-reactivity with the unrelated major grass allergen Phl p 4 [1].

Biochemistry

Amb a 1 is a monomeric, non-glycosylated protein with a molecular weight of 38 kDa, belonging to pectate lyase protein family [1, 4, 9]. Pollen pectate lyases are involved in pollen tube growth [9]. Amb a 1 represents 54 - 78% of A. artemisiifolia pollen allergenic molecules and 90% of its allergenic potential [13, 15, 16]

Isoforms, epitopes, antibodies

As of January 8, 2022, five isoallergens of Amb a 1 have been included in the World Health Organization (WHO) and International Union of Immunological Societies (IUIS) Allergen Nomenclature [4]. Sequence identity between Amb a 1 isoallergens is 63-87%, supporting IgE and T-cell epitope cross-reactivity, as well as distinct epitopes and immunological effects [3, 17].

Cross-reactivity due to structural similarity

Amb a 1 shares 44-59% sequence identity with other allergenic pectate lyases, namely Cup a 1/Jun a 1, Cry j 1, Art v 6 [9]. However, cross-reactivity does not occur with pectate lyases from Cupressaceae pollen (Cup a 1/Jun a 1 and Cry j 1), but only within the Asterales order, i.e. with Art v 6 [9]. Amb a 1 displays IgE and T-cell epitope cross-reactivity with pollen homologues from other ragweed species, such as A. psilostachya and A. trifida, in line with species-level cross-reactivity [16, 18].

Marker allergen for sensitization to Ambrosia sp pollen

Amb a 1 sensitization is found in 95-97% of patients with A. artemisiifolia pollinosis [1]. In areas of concomitant sensitization to Artemisia vulgaris or other weeds and overlapping pollination seasons, Amb a 1 assists with the identification of the primary sensitizer [1, 9, 12]. Amb a 1

Cross-Reactivity

Amb a 1 does not cross-react with pectate lyases from Cupressaceae pollen: Cup a 1/Jun a 1 and Cry j 1 [9]. Its reactivity is limited to pectate lyases from Asteraceae pollen (Art v 6, Hel a 6) and Phl p 4 [1, 9, 14].

AIT Prescription

Amb a 1 is a marker of A. artemisiifolia sensitization and can therefore aid in the decision process for AIT prescription [1]. On the therapeutic side, Amb a 1 was described as early as 1968 as an efficient AIT molecule [3]. 

Exposure

The main route of exposure is through inhalation of A. artemisiifolia pollen, especially at high levels of exposure [1]. 

Author: Joana Vitte

Reviewer: Dr. Christian  Fischer

Last reviewed:February 2022.