t222 Arizona cypress

Allergens within Tree Pollens

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  • Latin name: Cupressus arizonica
  • Family: Cupressaceae
  • Common names: Arizona cypress, Arizona Rough cypress, Cedro Blanco
  • Source material: Pollen
About 30 Arizona cypress tree varieties exists, recognised on the basis of distribution and foliage, and cone and bark characteristics.
 
Pollen
A tree species producing large amounts of pollen, which often induces hayfever, asthma and conjunctivitis in sensitised individuals.

Allergen Exposure

Geographical distribution
Arizona cypress is the only cypress native to the southwest of North America and has been widely exported, especially to Europe. It is a steeple-shaped, coniferous evergreen that can grow over 25 m tall. Its leaves are pale-green to gray-blue. The small, inconspicuous yellow flowers are monoecious (individual flowers are either male or female, but both sexes can be found on the same plant) and are pollinated by wind. The brown bark peels in thin strips and turns gray with age.
The taller, greener, more long-lived but closely related and, where pollen allergy is concerned, very similar Italian Funeral cypress tree is indigenous to the Mediterranean and has been introduced in places such as Australia, the US, New Zealand, Chile, China and India. It is the classic ornamental in cemeteries, a usage dating back to ancient times.
 
The Italian cypress tree is the leading cypress in the countries around the Mediterranean, followed by the Arizona cypress, and their prevalence is reflected in the allergic impact of their pollen. In the USA, Mountain cedar (another member of the Cupressaceae family, and one that in Europe exists only in the Balkans and the Crimea) is a major cause of seasonal allergy in the southwest (1-2) overshadowing the effects of Arizona cypress.
 
Environment
The Arizona cypress, like a number of other cypresses (including Italian Funeral cypress), is typically used as a windbreak, privacy screen or ornamental, or for erosion prevention. It is sometimes grown as a Christmas tree in the southern and western United States. The species can found in coniferous woodlands on rough, very dry and very rocky soils. It is also extensively cultivated.
 
Allergens
Allergens from the Arizona cypress tree have been isolated and characterised, and their diagnostic significance has been established (3). Cupressaceae pollen in general has 2 important characteristics: a low protein concentration and a high carbohydrate content.
  • Cup a 1, a 43-kDa protein, a major allergen, a pectate lyase (4-9, 26). Cup a 1 was demonstrated to be a major allergen: 19 of 33 sera (57%) from patients allergic to cypress showed significant reactivity to purified Cup a 1 (7).
     
  • Cup a 1.02, an isoform (10).
     
  • rCup a 1 (6) (10)
     
  • Cup a 3, a 21 kDa thaumatin-like protein, a major allergen (11, 12).

Sixty-three percent of 104 cypress-allergic patients were shown to have specific IgE against rCup a 3. The increased expression of Cup a 3 was reported to be dependent on the pollution in the area where the pollen was collected.

In a study investigating allergens of Italian Funeral cypress and Arizona cypress, the former showed a wider diversity of allergens, whereas the latter showed a higher content of the major 43 kDa allergen (13).
 
A recent study reported that a large number of sera from Arizona cypress-allergic individuals reactive with the major allergen recognise carbohydrate epitopes only. IgE from these sera were able to induce histamine release from basophils, and the authors suggest that they might play a functional role in the clinical symptoms of allergy (10). A large portion of the IgE reactivity of Cupressaceae-allergic subjects was reported to be associated with sugar moieties of C. arizonica, which appear to be shared by bromelain and phospholipase A2, thus suggesting that the IgE of patients reacting with such epitopes probably react with beta 1 --> 2 xylose, alpha 1 --> 3 fucose and/or alpha 1 --> 6 fucose (5).

Potential Cross-Reactivity

An extensive cross-reactivity among the different individual species of the genus could be expected, and in fact there is a great deal of evidence that it occurs (14-15).
 
Intense cross-reactivity has been reported between Italian Funeral cypress tree, Arizona cypress tree and Mountain cedar tree (16). For example, for in vivo diagnosis of cypress allergy, Mountain cedar tree pollen extract demonstrated a sensitivity of 95%, a specificity of 100%, a negative predictive value of 96%, and a positive predictive value of 100% (1). While Italian Funeral cypress tree and Arizona cypress tree are commonly encountered in Mediterranean regions, Mountain Juniper tree is, in Europe, present only in the Balkans, but is a major cause of allergy in the USA.
 
C. arizonica and C. sempervirens extracts are highly cross-reactive at the IgE level and share a number of common epitopes. Two major IgE-reactive components of approximately 43 kDa and 36 kDa have been shown to be present in both (17). The 2 have complementary allergenic composition: C. sempervirens shows a wider diversity of allergens, whereas C. arizonica shows a higher content of the major 43 kDa allergen (13). The cross-reactivity between these two family members was reported to be due to the presence of periodate-sensitive as well as -resistant epitopes (18).
 
Extensive cross-reactivity also occurs with other family members. These include Prickly Juniper tree (J. oxycedrus), Japanese cypress tree/False cypress tree (Chamaecyparis obtuse), and Western Red cedar tree (Thuja plicata) (8).
 
Cup a 1, the major allergen of C. arizonica pollen, was shown to be highly homologous with the major allergens of Mountain cedar (Jun a 1), Japanese cypress (Cha o 1) and Japanese cedar (Cry j 1). The study, indicating different IgE reactivity with the glycosylated and non-glycosylated protein, suggests the importance of carbohydrate moieties in the IgE binding site (6).
 
Pollen from Juniperus oxycedrus (Prickly Juniper tree) has also been shown to have wide cross-reactivity with other family members (19). Recombinant Jun o 2, one of the allergens from this pollen, was shown to have significant sequence similarity to calmodulins. Immunoblotting inhibition tests showed that J. oxycedrus, J. ashei, C. arizonica, C. sempervirens, Parietaria judaica, Olea europaea, and Lolium perenne pollen extracts were able to inhibit IgE binding to rJun o 2 at different concentrations (20). The implication is that if a close cross-reactivity can be expected between J. oxycedrus and other members of the Cupressaceae, then there is a possibility that individuals allergic to Pareitaria judaica and other members of the Urticaceae (e.g., Stinging Nettle) could be cross-reactive to trees from this species (Ed.).
 
Similarly, a study reported that a high inhibition of IgE binding on Olive pollen extract was exhibited by Birch, Mugwort, Pine, and cypress pollens, suggesting the presence of proteins sharing common epitopes that can be recognised by sera from Olive-allergic individuals (21).
 
Cup a 3 from Arizona cypress, a thaumatin-like stress-activated protein, has homology with a similar allergen found in Mountain cedar tree (Jun a 3), Cherry (Pru a 2), Apple (Mal d 2), and viral-infected Tobacco leaves (11). The amino acid sequence of Cup a 3 was found to have a high degree of homology to Jun a 3 (11).
 
The similarities of amino-acid sequences and some complex glycan stuctures have been suggested as explaining the high degree of cross-reactivity among the Cupressaceae and Taxodiaceae families (7).

Clinical Experience

IgE-mediated reactions
Arizona cypress, in common with the other members of the Cupressaceae family, is an important source of allergens, causing winter respiratory allergies and commonly inducing symptoms of asthma, hayfever, and allergic conjunctivitis in sensitised individuals (6, 19) symptoms from the winter flowering may create confusion with symptoms from perennial allergens such as house dust mite (22).
 
The Cupressaceae pollen season has gained an earlier onset as a result of the vastly wide distribution of C. arizonica, which pollinates in January and February and partially overlaps with the very highly cross-reacting C. sempervirens, which pollinates from February to the end of March (23). In a study over an 8-year period (1982-1989) in southern Italy, Cupressaceae pollen was noted to be at the highest during winter and early spring. “Remarkable” fluctuations of Cupressaceae pollen counts were noted over a 2-year cycle (29).
 
To initially demonstrate the cosmopolitan nature of C. arizonica and of its effects, we can point to a report of a 37-year-old man from Lithuania working in Switzerland who presented with the typical symptoms of allergic rhinoconjunctivitis that appeared in spring. A detailed history revealed that the patient was working in a building of a United Nations agency surrounded by a park with numerous Arizona cypress trees. Skin-specific IgE for C. arizona was strongly positive (24).
 
In general, species of the Cupressaceae family (Cupressus, Juniperus, Chamaecyparis, Callitris, Thuja and Libocedrus) are a very important cause of allergies (especially oculo-rhinitis) in various geographical areas, including North America, Japan, and Mediterranean countries such as France, Italy and Israel (25). Of particular importance is the wide diffusion in these countries of trees belonging mainly to the genus Cupressus, especially C. sempervirens and C. arizonica (26). Cypress allergy has been reported since 1945 (27). C. arizonica and Juniperus sabinoides, or Mountain cedar, are key causes of respiratory allergies in Texas and the southwestern United States. In Australia, the culprit species is predominantly C. sempervirens. In Japan, the major pollen allergen source is the Japanese cedar (Cryptomeria japonica), a member of the closely related family of Taxodiaceae.
 
Clinical and aerobiologic studies show that the pollen map of Europe is changing as a result of cultural factors (e.g., wider international travel and evolving environmental management). During the last 30 years, C. arizonica has been widely used for reforestation, for wind and noise barriers, and ornamentally in gardens and parks. C. sempervirens and C. arizonica are common in southern Itally and France, C. alba is present in most parts of Italy, and C. lasoniana is used in the UK as a fast-growing evergreen (28). Of the Cupressaceae, the most widespread genus in southern Italy was found to be Cupressus, represented in particular by C. arizonica Green and C. Sempervirens L. The authors noted that the employment of these trees for reforestation and garden use had increased considerably in the last 40 years (29). An increase in the reactivity to Cupressaceae pollens has been described as well, possibly because the allergenic load is becoming greater. Air pollution may have contributed to this increase (25).
 
From the Mediterranean region comes the most dramatic evidence of recent increases in reactivity to Cupressaceae pollen. For example, in a comparative study of Cupressaceae, the annual mean pollen concentration in Lyon-Bron (temperate region) went from 4.5 pollen grains per cubic metre of air at the beginning of the 1980s to 13.7 pollen grains at the beginning of the twenty-first century (an increase of more than 200%); and in Montpellier (Mediterranean region), the concentration went from 43 pollen grains per cubic metre of air to 72 pollen grains during the same period (30).
 
Similarly in Rome, the incidence of cypress allergy increased from 9.3% to 30.4% in 3 years (31). In Italy, the annual sensitisation rate as demonstrated by skin-specific IgE to C. sempervirens increased from 7.2% in 1995 to 22% in 1998 (32). In another large-scale study, allergy to Cupressaceae pollen was also reported to appear to be on the increase in recent years in Italy (22). In an epidemiological survey, conducted in 12 Italian centres, of 3057 pollen-sensitised patients, the prevalence of skin-specific IgE to a panel of tree pollen was found to be 9.2% in northern, 28.2% in central, and 20.1% in southern Italy. Monosensitised patients represented only 14.7% of all Cupressaceae-sensitised patients, their average age being higher than that of the polysensitised ones (43.3 versus 35.86). The most frequent allergens as shown by prick tests were Cupressus sempervirens (90%) and Cupressus arizonica (88.9%). The authors concluded that pollen allergy to the Cupressaceae was on the increase in Italy (22).
 
Nevertheless, the prevalence of cypress sensitisation varies greatly, even though the conflicting data are consistently collected in geographical areas with abundant cypresses. Some authors have stated that cypress allergy is underestimated, as this is a winter pollen and pollen allergy may be characterised by symptoms mimicking “recurrent” viral infections (25, 33). Other researchers have claimed that the prevalence of sensitisation is low in spite of the high allergenic pollen load in the areas studied (2, 34).  For instance, in the Western Ligurian Riviera, cypresses are part of the spontaneous flora and are also cultivated and planted for ornamental and gardening purposes. Of 1735 patients, only 18 (1.04%) had positive skin-specific IgE to cypress. Of these 18 patients, only 5 were monosensitised, whereas the remaining 13 patients were polysensitised.
 
Rhinoconjunctivitis was the more frequent symptom. In patients with polysensitisation, symptoms were not clearly related to the cypress pollen season, but rather to other pollens. The Cupressaceae pollen counts were high during the pollen season, with a trend toward increasing during the previous 4 years. The data from this study show that the prevalence of sensitisation to cypress, at least in this geographic region, is very low despite the large diffusion of the source of pollens and the high pollen peaks. This contrasts partly with data reported in previous surveys (35). For instance, in a study performed in another area of the Ligurian Riviera (35) the rate of sensitisation was higher (2).
 
A possible explanation for the underestimation of the real prevalence of cypress allergy may be the difficulty of allergen extraction from the grains, which leads to the lack of good standardisation of the extracts. Another possible factor is genetic protection, especially in those populations in close contact with cypresses during centuries (36).
 
The majority of studies evaluated either cypress as a homogenous entity or Italian Funeral cypress. This may have influenced the results of some studies. In a 4-year Italian study of 1393 patients, utilising skin-specific IgE tests to C. sempervirens, an incidence of cypress allergy of approximately 10% was reported in the first 2 years, but rose to over 24% when C. arizonica pollen extract was added to the test. With further improvements in the study, 35.4% of patients in the final year of the study were shown to be allergic to cypress pollen. The study concluded that allergy to cypress is under-evaluated as a result of its winter seasonal appearance and that false-negative diagnosis may be made as a result of poor in vivo allergen extracts (33). The authors of another study concluded that the use of more than one extract of Cupressaceae and Taxodiaceae origin would increase the diagnostic sensitivity (22).
 
To examine individual regions outside Italy: Cypress pollen allergy is also very important in France. In a study of Cupressaceae pollen (C. sempervirens) and allergic individuals in Montpellier, the authors reported that individuals allergic to this pollen present with a high rate of conjunctivitis and a low rate of asthma (25).
 
Cypress allergy has also been reported in Spain, and Cupressaceae pollen is by far the most common pollen during the winter period (30%) in Cordoba. Cupressaceae pollen is the predominant pollen in areas such as Toledo, Barcelona and Madrid from January to April (11%), and it is the main cause of the so-called "winter allergic cold". The prevalence of positive skin prick test to C. arizonica extract is around 20% (37-40). In the study, the absence of monosensitisation was noted. Of adult pollen-allergic patients, 37% were allergic to Cupressaceae, as well as 18% of those with respiratory allergy (37).
 
In Israel, Italian Funeral cypress grows naturally, but millions of these trees were also planted in recent times, as well as Arizona cypress and a variety of other family members. Researchers reported that pollen release in some regions may vary from one locality to another by a month, depending on prevailing winds, water availability and other microclimatic conditions (41). In another Israeli study, patients with cypress allergy were reported to be symptomatic from February until April; 70% of them had rhinitis, 30% also asthma and 18% conjunctivitis. Sensitisation to this pollen in hayfever patients varied from 26% in Tel Aviv to 32% in Netzer-Sireni and 24% in lower Galilee. In the monosensitised patients, anti-cypress immunotherapy was successful (42).
 
Similarly, Arizona cypress pollen has increased in the air of Tuscon, Arizona, due to “greening” of the area with ornamentals and barrier plants (43). There is, however, a remarkable shortage of allergy-related studies of this tree where it is indigenous, in the United States.
 
Compiled by Dr Harris Steinman, harris@zingsolutions.com

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