w211 Par j 2

Summary

Par j 2 is a major allergen of the wall pellitory (Parietaria judaica) weed pollen. Par j 2 belongs to the nonspecific lipid transfer protein (nsLTP) family. Relevant cross-reactivity to Par j 2 is limited to Par j 1 and pollen homologues from other Parietaria species. Of note, Par j 2 does not cross-react with nsLTPs from other allergenic sources, including Pru p 3 from peach and Art v 3 from mugwort pollen. Therefore, Par j 2 sensitization is a marker of genuine sensitization to pollen from Parietaria.

Epidemiology

Worldwide distribution

The wall pellitory (P. judaica), a weed of the Urticaceae family, growing in Mediterranean and temperate areas, such as Central and Eastern Europe, parts of the United Kingdom, the United States, and Australia, is a frequent cause of pollen sensitization and allergy in the Mediterranean area and the Iberian Peninsula [1-3].

Par j 2 is a major P. judaica pollen allergen, binding IgE from 80% - 83% of patients allergic to P. judaica [1, 4, 5].

Among Italian subjects with a suspicion of airborne or food allergy, the prevalence of Par j 2 sensitization was 25.71%, ranking 6th among 75 allergenic molecules, and peaking around 35% in people aged 46-55 years [6]. At the low end, in Central Europe, the prevalence of Par j 2 IgE is low, reported at 0.9% in a population of pollen-sensitized patients with doctor-diagnosed allergy in the Czech Republic [7].

Monosensitization to Par j 2 was observed in less than 2% of Italian subjects [6].

Environmental Characteristics

Source and tissue

Par j 2 is mainly present in P. judaica pollen [4]. Airborne amounts of Par j 1 and Par j 2, the two major allergens of P. judaica, are correlated to Urticaceae pollen counts. Par j 1 and Par j 2 are found mainly in the breathable fine particulate matter (PM2.5) fraction, which may explain why asthma is a frequent manifestation of P. judaica allergy [8]

Risk factors

The main risk factor for developing sensitization to Par j 2 is exposure to P. judaica pollen or subcellular fragments [1, 8].

Clinical Relevance

Detailed information regarding P. judaica pollen allergy is available in the whole allergen section. P. judaica pollinosis is often associated with severe respiratory symptoms, such as asthma and/or severe allergic rhinitis [3, 9].

Disease severity and prediction

Detection of Par j 2 IgE confirms genuine sensitization to P. judaica, which is often associated with moderate/severe AR, and symptoms or diagnosis of asthma [9, 10]. Conversely, Par j 2 sensitization was detected in only 7% of weed allergic patients living in areas with low exposure to P. judaica pollen, pointing to genuine sensitization to other weed species than P. judaica [5]. In Italian patients, a cut-off level of 6.52 kuA/L for Par j 2 IgE has been proposed for discriminating P. judaica allergic patients from sensitized subjects, with a positive predictive value (PPV) of 94.7% and a negative predictive value (NPV) of 100% [11].

Regarding plant food allergy, Par j 2 is not involved in its pathophysiology or diagnosis [12, 13]. In fact, in patients with plant food allergy, detectable Par j 2 sensitization has even been associated with a lower prevalence of food-induced severe, systemic symptoms (odds ratio 0.64, p = 0.025) [10]

Cross-reactive molecules

Par j 2 shares partial cross-reactivity with the nsLTP Par j 1, another major allergen of P. judaica [3], but not with other nsLTP [1, 10]. Thus, it may be considered as unrelated to food nsLTPs from a clinical viewpoint [13].

Prevention and Therapy

Experimental trials

Not relevant.

Molecular Aspects

Biochemistry

Par j 2 has a molecular weight of 11 kDa [4] and is non-glycosylated in its native form [2]. Par j 2 belongs to the nsLTP family, with a globular conformation comprising four alpha helices stabilized by four disulfide bonds, conferring resistance to heating and acidic pH [4, 14].

Isoforms, epitopes, antibodies

As of December 1st, 2021, two isoallergens of Par j 2 have been included in the World Health Organization (WHO) and International Union of Immunological Societies (IUIS) Allergen Nomenclature [15].

Cross-reactivity due to structural similarity

Structural identity between Par j 2 and other nsLTPs such as Pru p 3 was recently reported to be higher than sequence identity, with similar folding, conserved disulfide bonds and a similar ligand-binding hydrophobic cavity [16]. 

Diagnostic Relevance

Marker allergen for genuine sensitization to P. judaica pollen

Par j 2 is a marker of genuine sensitization to P. judaica pollen, with excellent PPV and NPV  [1, 2]. The association of Par j 1 and Par j 2 for the diagnosis of P. judaica pollinosis has been suggested [3]. As Par j 2 does not cross-react with nsLTPs other than Par j 1, such as Pru p 3 or Ara h 9, Par j 2 must not be used as a marker of food nsLTP syndrome [12].

As Par j 2 does not cross-react with nsLTPs other than Par j 1, such as Pru p 3 or Ara h 9, Par j 2 must not be used as a marker of food nsLTP syndrome [12].

Recombinant Par j 2 suitable for P. judaica diagnosis can be obtained using bacterial, yeast, and insect expression vectors [3].

Cross-Reactivity

Par j 2 lacks cross-reactivity with other nsLTPs outside Par j 1 [1]. Moreover, no pattern of associated sensitization was observed in a large-scale study in Italian subjects [6], although some authors reported Par j 2 and Pru p 3 sensitization levels may display a low level of correlation of uncertain clinical relevance [17, 18].

AIT Prescription

Detectable Par j 2 IgE confirms genuine sensitization to P. judaica, hence assisting with AIT selection [1, 2]. Ongoing research shows that a combination of Par j 1 and Par j 2, or engineered hypoallergenic hybrids of Par j 1 and Par j 2, are promising approaches for future AIT in P. judaica allergic patients [3, 19].

Exposure

The main route of exposure is through inhalation of P. judaica pollen.

Compiled By

Author: Joana Vitte

Reviewer: Dr. Christian Fischer

Last reviewed: February  2022