Bumble bee

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Code: i205
Latin name: Bombus terrestris
Source material: Venoms
Family: Apidae
Common names: Bumble bee, Bumblebee, Humblebee
Other species of Bumble bee include Bombus impatiens,  B. occidentalis, B. canariensis and Bombus pennsylvanicus (American Bumble Bee).
 
Insect
An insect, which may result in allergy symptoms in sensitised individuals.

Allergen Exposure

Geographical distribution
Essentially all insects responsible for causing insect sting allergic reactions belong to the order Hymenoptera. This order comprises over 70 families and over 100,000 species. Although many Hymenoptera can sting, stings from 3 families are most common: the Apidae (bees), the Myrmicidae/Formicidae (ants), and the Vespidae (wasps). The Apidae are divided between the Bumble bees and the Honey bees.
 
The total number of Bumble bee species has been estimated to be around 250 (1). But since Bumble bees have considerable variation in colouring within a species, taxonomy is difficult.
 
Bumble bees are spread over much of the world but most common in temperate climates, especially Europe, Asia and North America. They are absent from most of Africa and the lowlands of India. There are a few native South American species, and a few naturalised species in New Zealand. The spread of Bumble bees is generally very broad because of introduction for use in commercial agriculture.
 
In comparison with Honey bees, Bumble bees are bigger, hairier and more varied in colour. They average about 1.5 to 2.0 cm in length, and are usually black with broad yellow or orange bands. Most authorities recognise 2 genera: Bombus, the nest-building Bumble bees, and Psithyrus, the parasitic Bumble bees or Cuckoo bumble bees. Psithyrus spp. are distinguished by the lack of the corbicula or pollen basket on the hind tibiae.
 
Female Bumble bees (workers and queens) have a stinging apparatus consisting of an acid (venom-producing) gland, a venom reservoir (sac), an alkaline gland (Dufor's gland), and the sting itself. In contrast to that of Honey bees, the stinging apparatus in Bumble bees has a stronger connection to the abdomen and less pronounced barbs. Therefore, Bumble bees can retract their sting from human skin and, unlike Honey bees, do not usually die after having stung. However, Bumble bees are not aggressive and do not sting unless disturbed in the proximity of their nests, or unless squeezed (2).
 
The venom of Bumble bees has not been analysed as thoroughly as that of Honey bees. Hymenopteran venom consists of low-molecular-weight substances (biogenic amines [histamine and dopamine], sugars, amino acids, etc.), peptides, and proteins. Table 1 summarizes the information on Bumble bee venom published to date (3-11). In contrast to Honey bee venom, Bumble bee venom contains no mellitin (10), but instead has polypeptides with a similar function called bombolitins. These amphiphilic substances have a unique structure and can degranulate mast cells and increase the enzymatic activity of phospholipases, similarly to mellitin or mastoparan and crabrolin from vespid venoms (12-13). The biological activities include mast cell degranulation, chemotaxis, kinin, and others.
 
Table 1
 

Component

Quantity

Species

Reference

Serotonine

Traces

Bombus terrestris

(4)

Acetylcholine

30 µg/venom reservoir

Bombus terrestris

(5)

Slow muscle-contracting factor

 

Bombus lapidaries

(5)

Putrescine

 

Bombus ignitus

(6)

Mast cell degranulating peptide

< 1 % of dry weight

Bombus pennsylvanicus

(7)

Bombolitins

25% of dry weight

Bombus pennsylvanicus

(8)

Citrate

6.5-8.2% of dry weight

Bombus fervidus,
Bombus pennsylvanicus

(9)

Proteins

15-30% of dry weight

Bombus impatiens, Bombus pennsylvanicus

(3, 10-11)

From: Bucher C, Korner P, Wuthrich B. Allergy to bumblebee venom. Curr Opin Allergy Clin Immunol 2001;1(4):361-5.

Environment
Bombus species are social bees; i.e., they live in organized groups. They often nest in the ground, commonly in deserted bird or mouse nests. Bumble bees are not only excellent pollinators in open air, but are especially well suited to greenhouses and tunnels, places where other bees cannot be used.

The use of Bumble bees reared in captivity for pollinating crops began in 1987. Since this time, their use in commercial crops, principally greenhouse Tomatoes, has spread rapidly. They are now in use in almost 40 countries for pollination of Tomatoes, Melons, Strawberries, Eggplant, Zucchini (Courgettes), Cantaloupe, Blueberries, Cranberries, Peaches, Apples, Kiwi fruit and many other crops. The most commonly used variety is Bombus terrestris, but B. occidentalis, B. impatiens, and B. canariensis are also used where appropriate.

Allergens
Less is known about the allergenic properties of venom proteins of these Bumble bees than about those of their Honey bee counterparts.

The total protein content in the venom of Bombus impatiens and Bombus pennsylvanicus has been estimated to be 52 and 145 µg, and the amount delivered per sting 10 and 31 µg, respectively (11).

The American bumble bee, B. pennsylvanicus, has been shown to contain a 95 kDa protein, an acid phosphatase of 39 kDa, a hyaluronidase of 38 kDa, a protease of 28 kDa, and a phospholipase A of 14.2 kDa. Other proteins identified include 4 with unknown enzymatic activity, 36 kDa, 33 kDa, 29 kDa and 22 kDa in size (probably fragments of the 95 kDa protein), and a number of smaller peptides. The protease of 28 kDa is not found in Honey bee venom. Sera from patients allergic to Bumble bee venom reacted most strongly to the hyaluronidase in 4 individuals, to the acid phosphatase in 1 individual, and to the phospholipase A in another individual. The phospholipase A had a 54% identity with phospholipase A from Honey bee venom (11).

In a more recent study (14), a 95 kDa protein was found in the European but not in the American bumble bee, nor in a Honey bee venom preparation. All the venom types evaluated had a 17 kDa and a 45 kDa protein, attributed to the phospholipase A and the hyaluronidase, respectively. Both types of Bumble bee venom, but not Honey bee venom, contained a 31 kDa -33 kDa protein. A 28 kDa protein, probably a protease (2), was detected in the American bumble bee venom preparation alone. Immunoblotting studies showed a heterogeneous pattern of sensitivity: 1 patient's serum reacted strongly only to phospholipase A, and another’s exclusively to hyaluronidase, whereas the sera of 2 other patients reacted with several Bumble bee polypeptides (14).

A study reported that Bombus terrestris venom contained phospholipase A2, venom protease, hyaluronidase, and acid phosphatase allergens, but that the protease and phospholipase A2 allergens contained IgE-reactive epitopes that were different from those seen in Bombus pennsylvanicus; and, furthermore, that Bumble bee venom phospholipase A2 and protease are antigenically distinct from Honey bee venom proteins. There are significant species group-specific epitopes on Bumble bee venom proteins (15).

A number of allergens have been characterised:
Bumble bee – B. terrestris

  • Bom t 1, previously known as Phospholipase A2 or PLA2, a phospholipase (11, 15).
  • Bom t 4, a serine protease (11, 15).

American bumble bee – B. pennsylvanicus

  • Bom p 1, previously known as Phospholipase A2 or PLA2, a phospholipase (11, 15-16).
  • Bom p 4, a serine protease (11, 15-17).
  • Bom p Acid Phosphatase (11, 15).
  • Bom p Hyaluronidase (11, 15).

Potential Cross-Reactivity

Although the venoms of Bumble bee were thought to be highly cross-reactive, Bumble bee venom contains several proteins not found in Honey bee venom, including tryptic amidase related to clotting enzymes and acrosin. A study concluded that, therefore, skin-specific IgE testing with Honey bee venom will detect almost all cases of Bumble bee venom allergy; however, serum-specific IgE with Bumble bee venom can detect additional cases of sensitisation (11). This is supported by a study demonstrating that Bumble bee venom phospholipase A2 and protease are antigenically distinct from Honey bee venom proteins, and that there are significant species group-specific epitopes on Bumble bee venom proteins (15).

Similarly, the venom serine proteases of Honey bee, Bumble bee, and Paper wasp have significant IgE binding activities, but the structures are poorly conserved even among the Apidae, suggesting little cross-reactivity among the protein portions (17).

In a study evaluating IgE cross-reactivity between Bumble bee venom and Honey bee venom, sera from venom-sensitised patients were tested for specific IgE against venoms from the European bumble bee (Bombus terrestris), the North American bumble bee (Megabombus pennsylvanicus), and the Honey bee (Apis mellifera). Bumble bee venom and Honey bee venom were shown to contain venom-specific IgE-binding epitopes, suggesting that immunotherapy using Honey bee venom may not be effective in all Bumble bee venom-allergic patients. Importantly, this study also demonstrated differences in IgE binding for venom from European and American bumble bees (14).

Hence, testing with Honey bee venom alone is now known to be insufficient for assessing a patient for hypersensitivity to Bumble bee venom, since at least Apis and Bombus phospholipases A2 are known to be partially antigenically cross-reactive (29).

Clinical Experience

IgE-mediated reactions
Hymenoptera venom allergy is a common problem in many parts of the world. It is most commonly caused by members of the families Apidae (Bumble bees, Honey bees), Vespidae (Wasps, Yellow hornets, Hornets) and Myrmicidae (ants). Hymenoptera stings account for more deaths in the United States than any other venom. Although allergic reactions to Honey bee stings are common, allergy to Bumble bee venom is an uncommon form of Hymenoptera venom allergy (2, 18). In a study of 403 patients with Hymenoptera allergy who could identify the offending insect, only 1 case of Bumble bee allergy was involved (18). However, in an earlier study in the USA (19), 6% of Hymenoptera venom-allergic patients attributed their reaction to Bumble bee stings. In a search of the medical literature, approximately 46 cases of Bumble bee allergy have been identified (20-22).

During the past decade, several cases of Bumble bee allergy in greenhouse workers and Bumble bee farm employees have been reported in Belgium and the Netherlands (23, 25, 26). As Bumble bees are increasingly used for the pollination of greenhouse plants, the prevalence of this allergy has been increasing (2, 15, 24, 25), and severe anaphylactic reactions to Bumble bee stings occur (26). Six patients with severe episodes of anaphylaxis, caused by stings of Bumble bees in an occupational setting, have been reported. Sensitisation to Bumble bee venom was confirmed by skin- and serum-specific IgE tests with purified Bumble bee venom (26). Similarly, 11 patients with severe occupational anaphylaxis caused by stings of Bumble bees were reported. Sensitisation to Bumble bee venom was confirmed by the presence of skin- and serum-specific IgE to Bumble bee (27).

Another risk group for Bumble bee allergy is scientists studying the behaviour of Bumble bees: Two cases of occupational immediate-type allergies to Bumble bee venom were described, and, although both nonatopic patients had a negative personal history of allergic reactions to Honey bee sting, specific IgE antibodies and a positive intradermal reaction to Honey bee venom were detected (28).

The clinical presentation, diagnosis and therapy of Bumble bee venom allergy are similar to other Hymenoptera venom allergies (2). Two distinct categories of Bumble bee-sensitive patients have been identified. One group derives its primary sensitivity from field stings and often has IgE antibodies that cross-reacts with Honey bee venom proteins. A second group are the occupationally exposed individuals, who often have specific IgE antibody responses that are restricted to Bumble bee venom proteins; their IgE antibodies rarely cross-reacts with Honey bee venom proteins (28-29).

Individuals with allergy to Bumble bee have also been reported to have a high frequency of sensitisation to pollen (25).

Other reactions
From a prospective study of 34 patients evaluated for the presence of acute or chronic arthritis related to beekeeping, it was reported that acute arthritis was observed in 10 patients. Pain, tenderness, joint swelling, and warmth were present in most cases, and a chronic arthropathy was noted in 32 patients. A radiological study showed periarticular soft tissue swelling, bone sclerosis, periostitis, bony erosions, subchondral cysts, geodes, osteophytes, and joint narrowing. The study concluded that beekeepers have joint disease, apparently related to bee stings. The aetiology of this disease was unknown, and mechanical trauma, venom compounds, infection, and foreign body synovitis were factors that the authors suggested might influence the pathogenesis of this syndrome, which they designated "beekeepers' arthropathy" (30). Whether this condition may be associated with Bumble bees is not known.

Compiled by Dr Harris Steinman, harris@zingsolutions.com

References

  1. Michener CD. The bees of the world. Baltimore: The Johns Hopkins University Press. 2000:1-913
  2. Bucher C, Korner P, Wuthrich B. Allergy to bumblebee venom. Curr Opin Allergy Clin Immunol 2001;1(4):361-5.
  3. Müller DR. Insect sting allergy. Stuttgart: Gustav Fischer 1990. p. 5.
  4. Welsh JH, Batty CS. 5-Hydroxytryptamine content of some arthropod venoms from stinging hymenoptera. Toxicon 1963;1:165-173
  5. Piek T.  Acetylcholine and an unidentified muscle-contracting factor in the venom of the bumble-bee, Bombus terrestris L. Comp Biochem Physiol 1983;75C:351-356.
  6. Nakajima T. Trace characterization of venomous animals. In: Annual reports on trace characterization. Fujimaga T (editor). (in ref.11425) Japan: Scientific Grant of Education pp. 174-76
  7. Agriolas A, Herring P, Pisano J. Amino acid sequence of bumble-bee MCD peptide: a new mast cell degranulating peptide from the venom of the bumble-bee Megabombus pennsylvanicus. Peptides 1985;6(Suppl. 3):431-436.
  8. Argiolas A, Pisano JJ. Bombolitins, a new class of mast cell degranulating peptides from the venom of the bumble-bee Megabombus pennsylvanicus. J Biol Chem 1985;260:1437-1444
  9. Fenton AW, West PR, Odell GV, Hudiburg SM, Ownby CL, Mills JN, Scroggins BT, Shannon SB. Arthropod venom citrate inhibits phospholipase A2. Toxicon 1995;33(6):763-70
  10. Hoffman DR. Allergenic cross-reactivity between honey-bee and bumble-bee venoms. [abstract] J Allergy Clin Immunol 1982;69:139
  11. Hoffman DR, Jacobson RS. Allergens in Hymenoptera venom. XXVII: bumblebee venom allergy and allergens. J Allergy Clin Immunol 1996;97(3):812-21
  12. Signor G, Mammi S, Peggion E, Ringsdorf H, Wagenknecht A. Interaction of bombolitin III with phospholipid monolayers and liposomes and effect on the activity of phospholipase A2. Biochemistry 1994;33(21):6659-70
  13. Peggion E, Mammi S, Schievano E. Conformation and interactions of bioactive peptides from insect venoms: the bombolitins. Biopolymers 1997;43(6):419-31
  14. Stapel SO, Waanders-Lijster de Raadt J, van Toorenenbergen AW, de Groot H. Allergy to bumblebee venom. II. IgE cross-reactivity between bumblebee and honeybee venom. Allergy 1998;53(8):769-77
  15. Hoffman DR, El-Choufani SE, Smith MM, De Groot H. Occupational allergy to bumblebees: Allergens of Bombus terrestris. J Allergy Clin Immunol 2001;108(5 Part 1):855-60
  16. King TP, Guralnick M. Hymenoptera allergens. Clin Allergy Immunol 2004;18:339-53
  17. Winningham KM, Fitch CD, Schmidt M, Hoffman DR. Hymenoptera venom protease allergens. J Allergy Clin Immunol 2004 Oct;114(4):928-33.
  18. Müller UR. Epidemiology of insect sting allergy. Monogr Allergy 1993;31:131-46.
  19. Barr SE. Allergy to hymenoptera stings. JAMA 1974;228(6):718-20
  20. Barnard JH. Severe hidden delayed reactions from insect stings. NY State J Med 1966; 66:1206-1210.
  21. Donnovan BJ. Anaphylactic shock and strong cardiac stimulation caused by stings of the bumble bee Bombus terrestris. NZ Entomol 1978;6:385-389
  22. Panasoff J. Occupational allergy to bumble bee venom. (Letter) Clin Exp Allergy 1993;23:878
  23. van der Zwan JC, van der Linden PW, de Maat-Bleeker F, et al. Anaphylactic systemic reactions after a bumble-bee sting. [Abstract] Allergy 1992;47(Suppl. 12):52
  24. Graft DF. Stinging insect hypersensitivity in children. Curr Opin Pediatr 1996;8(6):597-600
  25. Kochuyt AM, Van Hoeyveld E, Stevens EA. Occupational allergy to bumble bee venom. Clin Exp Allergy 1993;23(3):190-5
  26. de Groot H, de Graaf-in 't Veld C, van Wijk RG. Allergy to bumblebee venom. I. Occupational anaphylaxis to bumblebee venom: diagnosis and treatment. Allergy 1995;50:(7):581-4
  27. de Jong NW, Vermeulen AM, de Groot H. Allergy to bumblebee venom. III. Immunotherapy follow-up study (safety and efficacy) in patients with occupational bumblebee-venom anaphylaxis Allergy 1999;54(9):980-4
  28. Stern A, Wuthrich B, Mullner G. Successful treatment of occupational allergy to bumblebee venom after failure with honeybee venom extract. Allergy 2000;55(1):88-91
  29. Hamilton RG. Diagnosis of Hymenoptera venom sensitivity. Curr Opin Allergy Clin Immunol 2002;2(4):347-51
  30. Cuende E, Fraguas J, Pena JE, Pena F, Garcia JC, Gonzalez M. Beekeeper' arthropathy. J Rheumatol 1999;26(12):2684-90

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