nApi m 1 Phospholipase A2, Bee

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Code: k203
Allergen source: Allergen component purified from the venom of Honey bee  (Apis mellifera).

Allergen Exposure

Phospholipase A2 (PLA2) is one of the major allergens in honey-bee venom (1).

The natural range of the honeybee is thought to be Africa, Europe and the Middle East for A. mellifera and Japan, India and Indochina for A. cerona. Honeybees have been domesticated and spread throughout the world.

Honeybee is the only stinging Hymenoptera that almost always leaves its fluked stinger in the skin of the victim. The venom continues to pump into the victim until the venom sac is exhausted or the stinger removed.

Potential Cross-Reactivity

Venoms from bumblebees and honeybees are reported to be highly cross-reactive, which is consistent with the degree of structural similarity in the phospholipases, phospholipase A2 (1-4). No cross-reactivity with vespidae phospholipase A, phospholipase A1 has been reported (5).

Clinical Experience

Studies indicate that a large percentage of the general population (15-25%) can be sensitized to Hymentoptera venoms. In rural populations the frequency may be even higher indicating that the prevalence of specific IgE antibodies is related to the degree of exposure to the Hymenoptera. Systemic reactions occur in 0,15-5% of the general population and may occasionally be fatal (6-7).

Since the risk of bee sting allergy increases with the degree of exposure, beekeepers are at a high risk for bee sting allergy (8).
 
Review
Phospholipase A2 (PLA2) is one the major allergens in honey bee venom (1, 9-13) Exposure is by stings from provoked or threatened insects (honey bee stings). Beekeepers, their families and neighbors are subjects at risk.
 
Venoms from bumblebees and honeybees are reported to be highly cross-reactive, which is consistent with the degree of structural similarity in the phospholipases, phospholipase A2 (1-4). No cross-reactivity with vespidae phospholipase A, phospholipase A1 has been reported (5).
 
Studies indicate that a large percentage of the general population (15-25%) can be sensitized to Hymentoptera venoms. In rural populations the frequency may be even higher indicating that the prevalence of specific IgE antibodies is related to the degree of exposure to the Hymenoptera. Systemic reactions occur in 0,15-5% of the general population and may occasionally be fatal (6-7).

Since the risk of bee sting allergy increases with the degree of exposure, beekeepers are at a high risk for bee sting allergy (8).

Biochemical characteristics
Phospholipase A2 is a biochemically well-defined glycoprotein of 14-16 kDa, consisting of 134 amino acids It constitutes 12-14 % of the dry weight and is the major protein component in honey bee venom. (14-17)

Immunological studies
Phospholipase A2 (PLA2) is one of the major allergens in honey bee venom (1, 9-13).
 
PLA2 has been used in different variants to study and better understand the mechanism behind elicitation of a specific immune response against allergens.

Sera from some bee-allergic individuals were shown to contain IgE antibodies directed against the carbohydrate portion of PLA2 (14, 15).

At least three human CD4+ T cell epitopes have been identified on PLA2, and T cell proliferative responses to these appear to be greater in allergic than non-allergic individuals (16). Differences in the production of interleukin-4 and interferon-? have also been described for PLA2 specific human CD4+ T cell clones raised from allergic and normal donors (18-19).

Diagnostic sensitivity and specificity of native and recombinant PLA2 compared to honey bee venom has been investigated (11). In specific IgE determination (Pharmacia CAP SystemTM) sensitivity was 86% for native PLA2 and 78% for recombinant PLA2 compared with 96% for honey bee venom. There was an increase in specificity using PLA2, especially for recombinant PLA2, compared to honey bee venom.

Extensive studies have been made to find major peptide T cell epitopes of PLA2 that give no allergenic side-effects (tolerogenic) when used in immunotherapy of honey bee allergic-patients (17, 18, 20). Specific activation of peripheral T cells by different conformational variants of PLA2 and secretion of cytokines regulating IgE and IgG4 antibody formation has been extensivly studied during recent years (21-23). 

References

  1. Sobotka A, Franklin R, Valentine M, Adkinson NF, Lichtenstein LM. Honey bee venom: Phospholipase A as the major allergen. J Clin Allergy Clin Immunol 1974;53:103.
  2. Hoffman DR, Jacobson RS. Allergens in Hymenoptera venom XXVII: Bumblebee venom allergy and allergens. J Allergy Clin Immunol 1996;97:812-21.
  3. 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;53:769-77.
  4. Annila I. Bee venom allergy. Clin Exp Allergy 2000;30:1682-87.
  5. King TP, Spangfort MD. Structure and Biology of Stinging Insect Venom Allergens. Int Arch Allergy Immunol 2000;123:99-106.
  6. Fernadez J, Blanca M, Soriano V, Sanchez J, Juarez C. Epidemiological study of the prevalence of allergic reactions to Hymenoptera in rural population in the Mediterranean area. Clin Exp Allergy 1999;29:1069-74.
  7. Müller UR,. Entomology of the Hymentoptera. Clinical presentation and Pathogenesis. Diagnosis and Treatment Stuttgart, New York: Gustav Fischer, 1990, 3-65.
  8. Eich-Wanger C, Müller UR, Bee sting allergy in beekeepers. Clin Exp Allergy 1998;28:1292-98.
  9. Sobotka AK, Franklin RM, Adkinson NF, Valentine MD, Baer H, Lichtenstein LM. Allergy to insect stings II. Phospholipase A: The major allergen in honeybee venom. J Allergy Clin Immunol 1976;57(1):29-40.
  10. Hoffman DR, Shipman WH. Allergens in bee venom. I. Separation and identification of the major allergen. J Allergy Clin Immunol 1976;58:551-62.
  11. Arbesman CE, Reisman RE, Wypych JI. Allergenic potency of bee antigens measured by RAST inhibition. Clinical Allergy 1976;6:587-94.
  12. Sobotka AK, Adkinson NF, Valentine MD, Lichtenstein LM. Allergy to insect stings IV. Diagnosis by Radioallergosorbent test (R.A.S.T.). J Immunol 1978;121(6):2477-84.
  13. Jarisch R, Yman L, Boltz A, Sandor I, Janitsch A. IgE antibodies to bee venom, phospholipase A, melittin and wasp venom. Clinical Allergy 1979;9:535-41.
  14. Weber A, Schröder H, Thalberg K, März L. Specific interaction of IgE antibodies with a carbohydrate epitope of honey bee venom phospholipase A2. Allergy 1987;42:464-70.
  15. Tretter V, Altmann F, Kubelka V, März L, Becker WM. Fucose a1,3-linked to the core region of glycoprotein N-glycans creates an important epitope for IgE from honeybee venom allergic individuals. Int Arch Allergy Immunol 1993;102:259-66.
  16. Carballido JM, Carballido-Perrig N, Kägi M et al. T-cell epitope specificity in human allergic and nonallergic individuals to bee venom phospholipase A2. J Immunol 1993;150:3582-91
  17. Akdis CA, Akdis M, Blesken T, Wyman D, Alkan SS, Muller U, Blaser K. Epitope-specific T cell tolerance to phospholipase A2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro. J Clin Invest 1996;98(7):1676-83.
  18. Carballido JM, Carballido-Perrig N, Terres G, Heusser CH, Blaser K. Bee-venom phospholipase A2-specific T cell clones from human allergic and non-allergic individuals: cytokine patterns change in response to the antigen concentration. Eur J Immunol 1992;22:1357-63
  19. Müller U, Fricker M, Wymann D, Blaser K, Crameri R. Increased specificity of diagnostic tests with recombinant major bee venom allergen phospholipase A2. Clin Exp Allergy 1997;27:915-20.
  20. Muller U, Akdis CA, Fricker M, Akdis M, Blesken T, Bettens F, Blaser K. Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell allergy in patients allergic to bee venom. J Allergy Clin Immunol 1998;101(6, pt 1):747-54.
  21. Wyman D, Akdis CA, Blesken M, Akdis M, Crameri R, Blaser, K. Enzymatic activity of soluble phospholipase A2 does not affect the specific IgE, IgG4 and cytokine responses in bee sting allergy. Clin Exp Allergy 1998;28:839-49.
  22. Akdis CA, Blesken T, Wyman D, Akdis M, Blaser K. Differential regulation of human T cell cytokine patterns and IgE and IgG4 responses by conformational antigen variants. Eur J Immunol 1998;28:914-25.
  23. Blaser K. Allergen dose dependent cytokine production regulates specific IgE and IgG antibody production. Adv Exp Med Biol 1996;409:295-303.

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