rHev b 1 Latex

Code: k215
Latin name: Hevea brasiliensis
Source material: rHev b 1 is a CCD-free recombinant protein
Common names: Rubber elongation factor (REF)

Latex allergen components

Available ImmunoCAP:

 

  • k215 rHev b 1*
  • k217 rHev b 3*
  • k218 rHev b 5
  • k220 rHev b 6.02*
  • k221 rHev b 8*
  • k224 rHev b 11*

 

*MBP fusion protein

Summary

Natural latex is a milky sap produced by over 2,000 plants, whereas the Latex that is used industrially is derived almost exclusively from the rubber tree Hevea brasiliensis. Ammonia is added to the sap as a preservative at the time of harvesting. Processing of Natural latex results in Natural rubber latex (cis-1,4-polyisoprene). Many chemicals are added to Natural latex before, during and after processing, including antioxidants, emulsifiers, stabilisers and accelerators. Processing converts the sap into liquid Latex concentrate or solid dry rubber. Latex concentrate is used to make items such as gloves, condoms, balloons, catheters, baby pacifiers, and dental dams. Dry rubber is the essential ingredient in tires, tubing, hoses, footwear, automotive components, engineering parts, and adhesives. Latex concentrate contains about 1% total protein, of which a small fraction remains in the manufactured product. This protein is responsible for IgE-mediated reactions. Dry rubber, however, contains very little protein and therefore is much less immunogenic. Besides Latex protein, additives from the manufacturing process such as mercaptobenzothiazoles, carbamates, and thiurams may form haptens and act as allergens.

True Latex allergy develops from plant protein in the Latex sap itself, whereas concomitant allergies may also develop from the chemicals added during processing. An individual may have concomitant allergies, such as an IgE-mediated allergy to Latex proteins and a lymfocyte-mediated hypersensitivity to carbamates. Carbamates may be found in some non-Latex substitutes recommended for Latex-sensitive individuals. A third type of reaction is an irritant contact dermatitis, which is often associated with Latex but not caused by Latex itself, and may result, for example, from the alkaline pH found in many powdered gloves.

Natural rubber products must be distinguished from items manufactured with synthetic rubber, such as butyl rubber and neoprene (polymers of 2-chlorobutadiene), which pose no risk to persons sensitised to natural rubber proteins.

In general, the Latex serum obtained by centrifugation may be quite variable in its protein content, depending on the treatment of the Latex after collection from the rubber tree as well as on the considerable batch-to-batch variation in the protein content of the rubber tree sap due to genetic or environmental factors (1). Latex allergen content may vary widely even in the same product, with a variance of 3,000-fold having been documented for Latex gloves obtained from 10 separate manufacturers (2).

Rubber latex contains more than 200 proteins. Ultra-centrifugation of the fresh Latex sap results in as many as 9 fractions, of which 3 are most easily discerned: the rubber particle proteins, the C-serum and the bottom fraction (B-serum). Rubber particle proteins are water-insoluble. Most of the C-serum and B-serum proteins are water-soluble (1).

Rubber particle proteins

The rubber particle proteins comprise the rubber particles and 2 main insoluble proteins, which are extractable from the surface of the rubber particles. Two allergens have been identified, Hev b 1 and Hev b 3, both major allergens and strongly associated with Latex allergy in spina bifida (SB) patients (1).

C-serum proteins

Latex C-serum contains various proteins (more than 200 polypeptides), of which some are enzymes associated with rubber biosynthesis. Four characterised Latex allergens, Hev b 5, Hev b 7.02, Hev b 8, and Hev b 9, belong to the group of C-serum proteins, which are present in the cytosol fraction of the Latex. The most important allergen of this subgroup is Hev b 5, a heat-stable protein (1).

B-serum proteins

B-serum contains a smaller number of proteins, among which hevein is the most prominent and makes up more than 50% of the total soluble B-serum proteins. B-serum currently includes a group of 9 characterised Latex allergens (Hev b 2, Hev b 4, Hev b 6.01, Hev b 6.02, Hev b 6.03, Hev b 7.01, Hev b 10, Hev b 11, Hev b 13), which are extra-cytosolic proteins. With the exception of Hev b 7.01, all belong to the group of plant defense proteins. A tenth allergen belonging to this group is Hev b 12, a lipid transfer protein (1).

Natural rubber latex-allergenic proteins include those involved in the biosynthesis of polyisoprene and the coagulation of Latex rubber elongation factor, small rubber particle protein, prohevein, and patatin. Structural and pathogenesis-related proteins include beta-1,3-glucanases, endochitinases (chitinase), hevamine, microhelix protein complex, proline-rich protein, profilins, enolases, and manganese superoxide dismutase (3). Other proteins isolated include proteasome subunit C5, malate dehydrogenase, and triosephosphate isomerase (4-5). Recently, a number of other proteins with allergenic activity have been isolated: Hev b Thioredoxin h, Hev b UDPGP (a UDP-glucose Pyrophosphorylase),

Hev b Citrate-binding protein, Hev b Hevamine (a chitinase), Hev b IFR (an isoflavone reductase), and Hev b Rotamase (a cyclophilin) (6).

Latex allergy occurs more frequently among individuals heavily exposed to natural rubber latex (NRL) products, including healthcare workers (HCW), laboratory workers, food handlers, hairdressers, cleaning staff and rubber industry workers. Children with neural tube defects such as SB have a particularly high prevalence of Latex allergy. Latex-sensitive persons with spina bifida have been shown to react preferentially to Hev b 1 and Hev b 3 proteins, whereas Latex-sensitive healthcare workers are more apt to be sensitised to Hev b 5 and Hev b 6.

Latex allergy is perhaps more complex than many other allergies in that it stems not from a single protein, but from no fewer than 13 known Latex allergens, with no single allergen deemed to be dominant. Sources of NRL are of varying quality and difficult to standardise for diagnostic purposes. As most Latex-allergic patients are sensitised to more than one Latex allergen, a blend of a number of allergens allows the identification of a greater number of Latex-allergic patients (7). Recombinant allergens may therefore be of great value in composing an appropriate blend of for more exact diagnosis.

Hev b 1 and the homologous Hev b 3 are associated mainly with young SB patients, whereas Hev b 5, Hev b 6 and Hev b 7 are linked more to adult Latex-allergic patients (8). A recent review study reported that native Hev b 2, recombinant Hev b 5, native or recombinant Hev b 6, native Hev b 13, and possibly native Hev b 4 are the major allergens relevant to Latex-sensitised adults (7).

There has been a number of epidemiological studies of varying subject sizes, many attempting to determine which proteins behave as major allergens in different risk groups.

In a study evaluating sensitisation to Latex allergens in HCW with histories of Latex allergy, Hev b 2, Hev b 5, Hev b 6.01, and Hev b 13 produced positive skin reactions in more than 60% of subjects, with Hev b 1, 3, 4, and 7.01 eliciting reactions in less than 50%. Specificity of 7 Hev b allergens was 100% in identifying workers with confirmed NRL allergy, and 98% for Hev b 13 (9).

A study population of 38 Latex-allergic and 15 SB Latex-sensitised children showed that natural Hev b 1 was recognised by 82% and natural Hev b 3 by 79% of the SB Latex-allergic children. Fifteen (39.5%) of 38 Latex-allergic and 2 (13%) of 5 SB Latex-sensitised children demonstrated IgE binding to natural Hev b 7. Further studies including rHev b 7 demonstrated that Hev b 7 was a third SB-associated Latex allergen (10).

The relative propensities for IgE binding to individual Latex allergens, compared using sera from Latex-allergic patients, found that IgE antibody binding to Hev b 4, Hev b 7b, Hev b 5 and Hev b 2 occurred in 75, 61, 31 and 28% of the study group, respectively. Multiple allergen sensitisation was common: of the 31 sensitised patients, 23 (74%) had specific IgE directed against at least 2 Latex allergens, while 12 (39%) had IgE antibodies for at least 3 allergens. The data suggested that many patients might have acquired sensitivity to Hev b 2, Hev b 4 and Hev b 7b from Latex products. Sensitivity to Hev b 5 and to Hev b 7c were interrelated and thought to have been acquired from sources other than Latex products, i.e., from certain foods (11).

Using purified Latex allergens, Hev b 1, 2, 3, 4, 6 and 7, allergen-specific IgE was demonstrated in 32-65% of HCW and 54-100% of SB patients with Latex allergy. Using a combination of Hev b 2 and Hev b 7, 80% of HCW and 92% of SB patients with Latex allergy were identified by ELISA technique, but the combination gave lower positive rates when IgE antibody tests were used. The addition of Hev b 3 allowed the detection of allergen-specific IgE in all SB-Latex allergic patients (12).

A study comparing skin reactivity of 6 recombinant Latex allergens with NRL proteins in 31 Latex-allergic individuals found that rHev b 2, 3, 5, 6, 7, 8 were positive in at least one Latex-allergic patient. Sensitisation to the various recombinant allergens was similar to that shown by previous studies using the native proteins. The use of a combination of recombinant Latex allergens, Hev b 5, 6 and 7, diagnosed Latex allergy with 93% sensitivity and 100% specificity (13).

The IgE antibody pattern has also been shown to differ between children with Latex allergy who have not undergone surgery and those with a history of multiple operations. The major allergens in children with no history of surgery appear to be Hev b 6.01 and Hev b 6.02 and not Hev b 1, a finding similar to that reported for HCW with allergy to Latex (14).

Therefore, one or a combination of Latex recombinant allergens may be used to easily determine allergen sensitisation profiles in different groups of Latex-allergic patients. Natural and recombinant allergens may also be used for assessing the allergenic potential of glove samples. A study detected all 6 Latex allergens tested for in at least some of the glove samples; Hev b 5 and Hev b 13 were identified as the marker allergens that combined best to explain the variation in the glove allergenicity. The study concluded that the overall allergenic potential of Latex gloves could be estimated by using Hev b 5 and Hev b 13 as indicator allergens. The correlation between glove allergenicity and the level of these allergens was maintained for low-protein gloves (<200 µg/g) (15).   

 

Immunological and clinical properties of characterised Latex allergens. Listed by IUIS*

Latex allergen

 

 

Significance as
Latex allergen

 

 

Significance of
cross-reactivity

 

 

IgE-binding prevalence
of the allergen

 

 

Documented
on k82 Latex ImmunoCAP

 

 

Hev b 1 High (especially in
spina bifida patients)
Not observed yet HCW: 55/105 (52%)
SB: 56/69 (81%)
++
Hev b 2 Medium Medium

HCW: 20/31 (65%)
SB: 7/13 (54%)

 

 

++
Hev b 3

High (especially in
spina bifida patients)

 

 

Not observed yet HCW: 13-20%
SB: 76-78%
++
Hev b 4 Not determined Not observed yet No clear results nt
Hev b 5 High in all risk
groups: GCW, spina
bifida, atopics
Not observed yet
(structural homology
with a Kiwi fruit
protein)
HCW: 68-92%
SB: 33-66%
++
Hev b 6.02 High in all risk
groups: GCW, spina
bifida, atopics
High (especially
with Banana, Kiwi,
Avocado, etc.; main
IgE-binding epitope)
LAP: 24/43 (56%)
HCW: 48/64 (75%)
SB: 3/11 (27%)
++
Hev b 6.03 High in context with
Hev b 6.01
High (structural
homology to plant
stress proteins)
LAP: 3/20 (15%)
LAP: 11/52 (21%)
nt
Hev b 7.01 Low-Medium Unclear (structural
homology to proteins
from Potato and
Tomato, but no cross-
reactivity with Banana
and Avocado)
LAP: 4/35 (11%)
LAP: 17/35 (49%)
++
Hev b 7.02 Medium only in SB Unclear - see
Hev b 7.01
SB: 15/30 (39.5%) ++
Hev b 8 Low (profilin is a
ubitiquitous pan-
allergen)
Medium LAP: 2/19 (11%)
HCW: 20-24%
SB: 6-12%
++
Hev b 10 Low Medium cross-
reactivity with
moulds
HCW: 0/20,
SB: 2/20
LAP: 4/15 (27%)
++
Hev b 11 Low High cross-
reactivity with fruit
allergens, especially
hevein-like sequences
LAP: 10/57 (19%)
LAP: (53 ???)
HCW (5SB): 17/58 (29%)
++
Hev b 12 Low Medium pan-allergen;
cross-reactivity with
fruits
LAP: 9/37 (24%) nt
Hev b 13 High Not determined yet HCWs by SPT: 39/62 (63%) nt

 


LAP = Latex-allergic patients
HCW = healthcare workers
SB  = spina bifida patients

++ Satisfactory amounts on k82 Latex ImmunoCAP™
+ Acceptable but low amounts on k82 Latex ImmunoCAP™
nt Not tested/not available
* International Union of Immunological Societies (www.allergen.org) Jan. 2008.

From: Rihs H-P, Raulf-Heimsoth M. Natural rubber latex allergens: Characterization and evaluation of their allergenic capacity. New Horizons, Phadia AB 2003; No 3.


k215 rHev b 1

Recombinant non-glycosylated MBP-fusion protein produced in an E. coli strain carrying a cloned cDNA encoding Hevea brasiliensis allergen Hev b 1

Common name: Rubber elongation factor (REF)
Biological function: Involved in biosynthesis of polyisoprene
Mw: 15 kDa

Allergen description

Hev b 1 (16-18), also known as rubber elongation factor (REF), is one of the most important Latex allergens and is a leading cause of Latex IgE-mediated allergy in children with spina bifida (SB) (19). Hev b 1 has also been shown to be an important allergen in healthcare workers (HCW) (20). It is a Latex-specific allergen without relevant homology to other plant proteins. Hev b 1 makes up 10% to 60% of the total protein found in Latex (3). Although Hev b 1 is not constantly found in Latex sap, it is the main protein found in Latex glove extract (21). In a laboratory where gloves are worn for protection, the use of Latex gloves resulted in a 26-fold increase in inhaled Latex allergen over background levels measured where vinyl gloves were worn as controls (22).

Hev b 1 is closely related to Hev b 3 (23). Both Hev b 1 and Hev b 3 are major water-insoluble proteins located on the surface of rubber particles in H. brasiliensis Latex.
Hev b 1 is found mainly on large rubber particles, and Hev b 3 mainly on small rubber particles. Both allergens bind IgE from patients with SB and Latex allergy (17).

Studies have reported a wide range of allergen-specific IgE binding to Hev b 1, with 54-100% of SB patients with Latex allergy reacting to Hev b 1, whereas a frequency of only 13-32% was observed in HCW (1).

In a study of serum from 140 SB patients as well as from 105 HCW allergic to Latex evaluated for sensitisation to highly purified Hev b 1, 81% with SB and allergic to Latex had IgE antibodies directed to Hev b 1, whereas antibodies to Hev b 1 were found in 52.3% of HCWs allergic to Latex (24).

Similarly, other studies have reported that Hev b 1 is a more prevalent allergen in SB Latex-allergic individuals than HCW Latex-allergic individuals. For example, 4 of 6 SB Latex-allergic children exhibited IgE antibodies against Hev b 1, compared to only 1 of 30 Latex-allergic patients (25).

SB patients have been reported to display a unique pattern of sensitisation: IgE reactivity is preferentially directed against Hev b 3 and Hev b 1, the 2 Latex allergens with high sequence similarity (26). In a study of 35 Latex-allergic patients with SB, 29 showed IgE binding to rHev b 3, as did 4 of 15 of the Latex-sensitised group. Hev b 3 is related to Hev b 1 by a sequence identity of 47%. Although cross-reactivity between these 2 Latex allergens was illustrated by the large extent of inhibition of IgE binding to nHev b 1 by rHev b 3 (27), no cross-reactivity between Hev b 3 and Hev b 1 has been shown at the T cell level (26).

Studies performed with recombinant Hev b 1 (rHev b 1) showed that 16 out of 71 Latex-allergic HCW (23%) had IgE antibodies to rHev b 1. This confirmed the results of studies performed with the native counterpart (18).

Although no major cross-reactivity has been reported to Hev b 1, in a study of cross-reactivity of IgE antibodies recognising epitopes of Latex allergens and papain in sera of 36 Latex-exposed subjects and 22 papain workers, it was reported that 8 of 24 Latex-sensitised individuals showed low or moderate levels of allergen-specific IgE to papain, and 6 of the 12 sensitised papain workers had serum IgE to Latex allergen(s). Comparison between the primary sequences of Hev b 1 and papain suggested that the cross-reactivity might be due to several identical trimers and tetramers (28). Further studies may clarify this relationship.

In summary, Hev b 1 is one of the major Latex allergens in SB patients and is of intermediate relevance in the risk group HCW.


k217 rHev b 3

Recombinant non-glycosylated MBP-fusion protein produced in an E. coli strain carrying a cloned cDNA encoding Hevea brasiliensis allergen Hev b 3

Common name: Small rubber particle protein, SRPP
Biological function: Involved in the biosynthesis of polyisoprene
Mw: 24 kDa

Allergen description

Hev b 3 (13,16,29) forms an integrated part of the “small rubber particles” (23). It has a significant role in rubber synthesis because of its ability to synthesise long-chain polyisoprene (3).

Hev b 1 is closely related to Hev b 3 (23). Both Hev b 1 and Hev b 3 are major water-insoluble proteins located on the surface of rubber particles in H. brasiliensis Latex. Hev b 1 is found mainly on large rubber particles, and Hev b 3 mainly on small rubber particles. Both allergens bind IgE antibodies from patients with spina bifida (SB) and Latex allergy (17).

Several studies with sera of Latex-sensitised SB patients showed IgE reactivity frequencies of 67-83% (1). The reason for these observed high frequencies might be due to stretches of high sequence homology between Hev b 3 and Hev b 1 (1).

Hev b 3 has been found to be an important allergen in SB patients, but in contrast, the reactivity to Hev b 3 is less frequent among health care workers (HCW) (30). In immunoblots 29/35 SB patients were shown to have allergen-specific IgE binding to rHev b 3, whereas this was only shown in 4 of 15 of the Latex-sensitised group. IgE epitopes on rHev b 3 were shown to abolish all IgE binding to nHev b 3. Hev b 3 is related to Hev b 1 by a sequence identity of 47%. Cross-reactivity between these 2 Latex allergens was illustrated by the large extent of inhibition of IgE binding to nHev b 1 by rHev b 3 (27). However, no cross-reactivity between Hev b 3 and Hev b 1 has been demonstrated at the T cell level (26).

rHev b 3 coupled to ImmunoCAP™ (Rk217) revealed a comparable frequency of 12.5% in 40 Latex allergic HCW tested (1).


k218 rHev b 5

Recombinant non-glycosylated protein produced in an E. coli strain carrying a cloned cDNA encoding Hevea brasiliensis allergen Hev b 5

Common name: Acidic protein
Biological function: Unknown, a structural protein
Mw: 16 kDa

Allergen description

Hev b 5 (11,13,31-34) is a potent Latex allergen and is heat-stable (35). Its physiological function is unknown. Hev b 5 exists as multiple isoforms, but only small amounts are present in the non-ammoniated Latex preparations, such as those used for diagnostic tests, and this may help to explain the relatively poor sensitivity of some in vitro tests (36). Therefore, most of the research has been performed with the recombinant form, rHev b 5. In serological tests, 92% of Latex-allergic adult health care workers (HCW) and 56% of the spina bifida (SB) Latex-allergic patients showed Hev b 5-specific IgE antibodies in their sera (32).

It has also been shown that rHev b 5 could be used as a complement reagent to enhance the quantitative performance of Latex ImmunoCAP™ for allergen-specific IgE measurement (37). A significant number (16%) of serum samples became more strongly positive to the improved k82 (spiked with rHev b 5) than to the regular k82 Latex ImmunoCAP™, and a rather small number of previously negative serum samples became positive (37). Hev b 5 may be the missing allergen to fill the diagnostic gap for some allergic patients with clear clinical Latex allergy but with negative serological reactivity (1).

Furthermore, Hev b 5-specific mono-clonal antibodies and human IgE from Latex-allergic HCW demonstrate the greater content of Hev b 5 in high-protein powdered glove extracts. This may explain the observed higher frequency of sensitisation to this allergen in HCW (33).

The nucleotide and deduced protein sequences or rHev b 5 have significant homology to sequences from Kiwi and Potato, which are known to cause allergic reactions in some Latex-allergic patients (32). The sequence homology (47% sequence identity) between these 2 acidic proteins suggests a molecular explanation for the high frequency of fruit hypersensitivity in Latex-allergic patients (38). A novel gene has been isolated from a Sugar beet cDNA library that resembles members of the Latex allergen Hev b 5 family (39). However, the clinical significance has not been established.

Hev b 5 has been identified as a potential candidate for immunotherapy. A recombinant Hev b 5 protein with significantly reduced IgE-binding activity has been described, and this may prove to be a valuable reagent for immunotherapy (31).

 

k220 rHev b 6.02

Recombinant non-glycosylated MBP-fusion protein produced in an E. coli strain carrying a cloned cDNA encoding Hevea brasiliensis allergen Hev b 6.02

Common name: Hevein
Mw: 5 kDa

Allergen description

Hev b 6.02 (41,51-52), hevein, is a small protein, which has been identified as the most common allergen for healthcare workers (HCW) allergic to Latex. About 75% of these workers allergic to Latex had hevein-specific antibodies (53). Hevein is not only a major IgE-binding allergen in Natural rubber latex (NRL) but also in other Latex manufactured products (42,54). Prohevein, Hev b 6.01, is cleaved naturally to yield 2 allergenic fragments, the N-terminal hevein, Heb b 6.02, and the C-terminal portion, Hev b 6.03 (3,42). All 3 allergens exist in the plant, although the ratio between Hev b 6.01 and Hev b 6.03 is about 30:1 (43). All 3 components act as independent allergens (41).

In a study, serum-specific IgE to hevein was detected by ELISA in 48 of 64 (75%) sera from HCW allergic to Latex, and in 3 of 11 (27%) sera from patients with spina bifida (SB) and hypersensitivity reactions to Latex. Skin-positive tests hevein was found in 17 of 21 (81%) patients with Latex allergy (55).

Hevein (Hev b 6.02) is the main allergen cross-reacting with Avocado in subjects with Latex allergy. Results of immunoblots and immunoblot inhibition with 11 serum samples confirmed that a 30-kDa protein in Avocado was the major IgE-binding component; the IgE-binding reactivity to this protein could be inhibited by hevein in all sera tested. Sixty-seven of 91 (73%) subjects from the HCW group and all 19 subjects in the SB group with positive IgE antibodies to hevein also had elevated IgE values to Avocado (53).

 

k221 rHev b 8

Recombinant non-glycosylated MBP-fusion protein produced in an E. coli strain carrying a cloned cDNA encoding Hevea brasiliensis allergen Hev b 8

Common name: Profilin
Biological function: Actin-binding protein
Mw: 14 kDa

Allergen description

Hev b 8 (13,56-58,60) is a profilin. Plant profilins are important panallergens. They are responsible for a significant percentage of pollen-related allergies. The observed frequencies of Hev b 8-specific IgE antibodies in sera of Latex-allergic patients in different risk groups range between 6 and 24% (1,57-58,60).

rHev b 8 has a sequence identity of 75% with Birch profilin (Bet v 2) (57). Recombinant isoforms of Hev b 8 with marginal differences in the amino acid sequence were reported to have no influence on the IgE-binding properties of the rHev b 8 isoforms. In a study evaluating the prevalence of serum IgE antibodies to rHev b 8, among 17 SB patients, IgE antibodies to rHev b 8 were found in 2, and in 5 of 25 sera (20%) from HCW. Further studies demonstrated the presence of IgE-binding epitopes on the Hev b 8 molecule which did not cross-react with Birch profilin. The study concluded that Latex profilin represents a minor allergen in Natural rubber latex (NRL) and may have IgE-binding epitopes different from Bet v 2 (58).

These factors may explain the variability in the prevalence of allergen-specific IgE binding to Latex profilin in studies. For example, skin tests and allergen-specific IgE antibodies to natural and recombinant purified Hev b 8 were positive in 15 of 17 spina bifida (SB) children and all 14 adults allergic to Latex. However, only 42% of the Latex-allergic patients had allergen-specific IgE levels of 0.35 kUA/L or higher, and only 39% of them exhibited IgE binding with any natural or recombinant Hev b 8 forms (56).

Between 30% and 50% of individuals who are allergic to Latex products are also allergic to specific plant foods, and this is aptly described as Latex-fruit syndrome. However, the roles of the Latex chitinase, Latex profilin and Latex beta-1,3-glucanase need to be clarified. This is well illustrated in a study, which reviewed simultaneous sensitisation to Latex and Bell pepper, sensitisation that had previously been reported. In sera of 4 patients with allergy to Latex and Bell pepper, 3 were shown to have IgE antibodies to profilin from Bell pepper and Latex. Two patients also had IgE antibodies to Hev b 2 (a beta-1,3-glucanase) and a homologous protein in Bell pepper. One patient was shown to have allergen-specific IgE to an L-ascorbate peroxidase, and another patient to a 38 kDa protein. The study concluded that Hev b 2 (beta-1,3-glucanase) and the Bell pepper L-ascorbate peroxidase were also cross-reactive allergens, and that profilin was responsible for some of the IgE cross-reactivity (59).

Similarly, other studies have demonstrated the variable responsibility of profilin in cross-reactivity between Latex profilin and other plant profilins. In a study of sera of 36 individuals containing IgE antibodies to Ragweed profilin, 35 reacted with profilin from Latex, indicating structural homologies between profilins from Latex and Ragweed. Fifty-nine percent of these sera were found to be positive for Latex-specific IgE. As profilin is also present in Banana, it was proposed that Latex profilin would likely be involved in cross-reactivity between Banana and Latex. However, among 19 individuals allergic to Latex, only 2 had anti-profilin IgE antibodies. The authors suggested that IgE antibodies to Latex profilin might be a questionable factor in sensitisation of occupationally exposed patients, but that sensitisation to profilin should be taken into account when interpreting the results of Latex-specific IgE investigation (60).

Recombinant profilin from Banana and Pineapple has a high sequence identity (71-84%) to known allergenic pollen and food profilin. In a study demonstrating IgE binding in sera to recombinant profilin, in 7/16 (44%) subjects with suspected Banana allergy, and in 8/19 (42%) subjects with suspected Pineapple allergy, high cross-reactivity to Birch pollen profilin Bet v 2 and Latex profilin Hev b 8 was demonstrated. Profilin was therefore shown to be an important mediator of IgE cross-reactivity between pollen and exotic fruits (61-62).

In a study using rHev b 8 to screen sera from Latex-allergic HCW with well-documented histories of food and pollen allergy and Latex-allergic SB patients, 12 of the 50 HCW and 2 of the 34 SB patients were sensitised to Hev b 8. All Hev b 8-sensitised patients showed allergic symptoms to pollen or plant foods. Cross-reactivity among profilins of Latex, pollen and plant food was demonstrated by their ability to inhibit IgE binding to rHev b 8. The authors concluded that primary sensitisation to Latex profilin in the majority of cases took place via pollen or food profilin, and that pollen- and food-allergic patients with profilin-specific IgE antibodies could be at risk of developing Latex allergy (57).

Other studies have also demonstrated the relevance of Latex profilin cross-reactivity, for example between Chenopodium profilin and Latex (65), and between 2 Rice profilin cDNAs (highly homologous to each other) and profilin from Maize, Bermuda grass, Timothy grass and Latex (63).

 
 

k224 rHev b 11

Recombinant non-glycosylated MBP-fusion protein produced in an E. coli strain carrying a cloned cDNA encoding Hevea brasiliensis allergen Hev b 11

Common name: Class 1 Chitinase
Biological function: Chitinase plant defence
Mw: 32 kDa

Allergen description

Hev b 11 (65-66) is a class 1 chitinase with an N-terminal chitin-binding domain with homology to hevein (3). Heb v 11 shows greater than 65% identity with several other plant endochitinases (7). Chitinases are abundant proteins found in a wide variety of seed-producing plants. Most chitinases hydrolytically degrade chitin which is a major structural component of the cell wall of many fungi and the exoskeleton of many insects (3).

rHev b 11.0102 has been reported to have a 56% homology to hevein. rHev b 11.0102-specific IgE antibodies were found in 17 of 58 sera (29%) of IgE-mediated Latex-allergic subjects. Due to its IgE-reactivity, rHev b 11.0102 was reported to represent an allergen of intermediate prevalence in Natural rubber Latex (NRL), and it was stated that its cross-reactive potential with certain fruit makes it an important supplement in the diagnostic panel of recombinant NRL allergens (65).

Class I chitinases from Chestnut, Avocado and Banana have been identified as relevant allergens. The chitin binding (hevein) domain from these class I chitinases is thought to contain the important IgE binding epitopes. The H. brasiliensis chitinase, Hev b 11, was shown to have a 70% identity with the endochitinase from Avocado, and the identity was 58% between its hevein domain and Hev b 6.02 (hevein). rHev b 11 bound IgE antibodies in Latex- and fruit-allergic patients in 19% of 57 patients.
The study concluded that Hev b 11, although having a chitin-binding domain, displays a different IgE binding capacity compared with hevein (66).

Similarly, a study of class I chitinases, evaluated for their potential role as cross-reactive allergens in Latex-food allergy, found polyclonal antibodies to chitinases in sera from patients with Latex-fruit allergy; the antibodies were in response to chitinases of Chestnut, Cherimoya, Passion fruit, Kiwi, Papaya, Mango, Tomato, and Wheat flour extracts. Prs a 1, the major allergen and class I chitinase from Avocado, was shown to strongly or fully inhibited the IgE binding of Latex chitinase. The study concluded that putative class I chitinases appear to be relevant cross-reactive components in foods associated with Latex-fruit syndrome, but do not play a specific role in allergy to Latex without a concomitant allergy to fruit (67).

Cross-reactivity has been described between Obeche wood dust and Latex. The Obeche allergen, Trip s 1, a class I chitinase, was homologous to Latex hevein (68).

Japanese cedar (Cryptomeria japonica) pollen allergy is one of the most prevalent allergic diseases in Japan. The cDNA high-frequency IgE-binding protein (CJP-4) cloned from C. japonica pollen was reported to have significant sequence homology to class IV chitinases and was able to bind IgE antibodies from all 31 patients tested by ELISA. Pre-incubation with latex C-serum completely inhibited the reaction to purified CJP-4 of pooled serum IgE antibodies from patients with C. japonica pollinosis and/or Latex allergy (69).

Compiled by Dr Harris Steinman, harris@zingsolutions.com

 

 

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As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.