Table 1 Optimal allergen concentrations
Rules for uptake into the list of optimal allergen concentrations
Table 1.1 Drug Allergy
Table 1.2 Environmental Allergy
Table 1.3 Protein allergens - Food
Table 1.4 Protein allergens – insect poison
Table 1.5 Protein Allergens - Inhalant
Selection criteria for tables 2 - 5
Table 2 Drug Allergy
Table 3 Food allergy
Table 3.1. Studies assessing the role of BAT in the diagnosis of food allergy
Table 3.2. Studies assessing the role of BAT in predicting the development of tolerance in food allergic children
Table 3.3. Studies using BAT to monitor the response to immunomodulatory treatments for food allergy
Table 4 Hymenoptera venom allergy
Table 4.1 Sensitivity and specificity of BAT, sIgE, SPT and DPT in insect venom allergy
Table 4.2 BAT with insect venom recombinants
Table 5 Inhalant Allergens
Reference list
Table 1 Optimal allergen concentrations
Rules for uptake into the list of optimal allergen concentrations
- Wherever possible, commercially standardized allergen preparations should be used.
- The indicated concentrations must have been used to document specific allergy (patient is positive, a control is negative)
- The source should be that which gave rise to symptoms, and should be indicated.
- Where possible, we should have a reference for use of the concentrations – it improves the information for users, and submitters chances of a citation.
- The table will be updated annually by volunteers
Table 1.1 Drug Allergy
Allergen / Source / concentration range / ReferenceBenzylpenicillin / 2 &0.4 mg/ml / (1)
Amoxicillin / 1.25 & 0.25 mg/ml / (1)
PPL / 0.25 & 0.05 mg/ml / (1)
MDM / 0.25 & 0.05 mg/ml / (1)
Cephalosporins / 1.25 & 0.25 mg/ml / (1)
ASA / 1 & 0.2 mg/ml / (2)
Diclofenac / 0.3 & 0.06 mg/ml / (2)
Naproxen / 1 & 0.2 mg/ml / (2)
Paracetamol / 1 & 0.2 mg/ml / (2)
Metamizol / 2.5 & 0.25 mg/ml / (2)
Atracurium / 0.5 &0.05 mg/ml / (3)
Vecuronium / 2-0.5 mg/ml / (3)
Pancuronium / 0.2 & 0.02 mg/ml / (4)
Rocuronium / 5 & 0.5 mg/ml / (3)
Suxamethonium / 5 & 0.5 mg/ml / (3)
Cisatracurium / 0.5 &0.05 mg/ml / (3)
Table 1.2 Environmental Allergy
Allergen / Source / Concentration range / ReferenceMalonic acid, organic acid anhydride / 0.2 & 0.04 mg/ml / (5)
Table 1.3 Protein allergens - Food
Allergen / Source / Concentration range / ReferenceCrude peanut extract / 0.1 ng/ml -1 ug/ml / E. Knol[1]
Crude peanut extract / 0,003ng/ml-1 ug/ml / (6)
Bet v 1, Bet v 2, Api g 1, Dau c 1 and Mal d 1 / BioMay, Austria / 1 -100 ng/ml / (7)
Ara h 2 / 0.1 ng/ml - 1 ug/ml / E. Knol1
Ara h 6 / 0.1 ng/ml - 1 ug/ml / E. Knol1
Ara h 1 / 1 ng/ml - 1 ug/ml / E. Knol1
Ara h 3 / 1 ng/ml - 1 ug/ml / E. Knol1
Celery / market / 0.01 – 1% w/vol / Dongo et al, EAACI 2014 Abstract 696
Turkey / market / 0.01 – 1% w/vol / Snefstrup et al, EAACI 2014 abstract 703
Table 1.4 Protein allergens – insect poison
Allergen / Source / Concentration range / Reference/PMID/lab nameBee and wasp venomextract / HAL Allergie / 1 ng/ml - 1 ug/ml / (8–11)
Wasp and Bee venom extract / ALK Aquagen / 0.1 ng/ml - 1 ug/ml / (12–15)
Wasp, Bee, Paper Wasp and European Hornet venom extract / BÜHLMANN Laboratories / 0,45 ng/ml -284 ng/ml / (16)
rVes v 1 / Sf9 insect cells / 0.1 ng/ml - 2 ug/ml / (17)
rApi m 5 and rVes v 1 / High Five or Sf9 insect cells / 0.08 ng/ml - 1 ug/ml / (18)
rApi m 10 / High Five or Sf9 insect cells,
E. coli / 0.1 ng/ml - 100 ng/ml / (19)
rVes v 1, 2, 3 and 5 / High Five insect cells / No data / (20)(111)
nApi m 1; rApi m 1, 2, 3, 5, 10 / Latoxan for native Api m1, Sf9 insect cells / 0.1 ng/ml - 10 ug/ml / Laboratory for Clinical Immunology & Molecular Genetics, University Clinic of Respiratory and Allergic Diseases Golnik
Table 1.5 Protein Allergens - Inhalant
Allergen / Source / Concentration range / ReferenceHouse dust mite extract / 0.1 ng/ml - 1 ug/ml / E. Knol1
Der p 1 / 1 ng/ml - 1 ug/ml / E. Knol1
Der p 2 / 1 ng/ml - 1 ug/ml / E. Knol1
Fel D 1 / ALK Alello / 0.5 ug/ml / (21)
rPhl p 1, rPhl p2, rPhl p 5, rBet v 1, and rBet v 2) / E. Coli / 10–7 to 10 μg/mL / (22)
rDer p 2 / ALK-Abello / 1 pg/ml - 100 ug/ml / (23)
Aquagen grass / ALK-Abello / 10 ng/ml - 1 ug/ml / (24)
Aquagen allergens; grass, birch, wasp, bee, cat, house dust mite / ALK-Abello / 0.00003 – 28 600 SQU/ml / (25,26)
Selection criteria for tables 2 - 5
Inclusion and exclusion criteria of studies used in the systematic literature search:
We included prospective, cross-sectional or retrospective studies in man of any age with a whole blood BAT to relevant allergen using flow cytometry that compared BAT to an accepted alternate test, preferentially to allergen provocation.
We excluded review articles, animal studies, studies exclusively using cell lines, mediator release assays or passive sensitisation basophil assays and studies using basophil activation test to detect the presence of relevant allergen in complex mixtures or to determine the biological activity of novel allergens.
Table 2 Drug Allergy
Author / PMID / Year / CD63 / CD203c / SPT/IDT / sIgE / BAT Sensitivity and Specificity
Betalactams
Abuaf N. (27) / 18331364 / 2008 / x / x / x / CD63: S=22%;SP=100%
CD203c: S=52%; SP=79%
De Weck AL. (28) / 19862935 / 2009 / x / x / x / S= 50%
SP= 89-97%
BAT in SPT negative: 37%
Sanz ML. (29) / 11929494 / 2002 / x / S= 50%
SP= 93.3%
Gamboa PM. (30) / 15736712 / 2004 / x / x / x / S=39.1%
SP=93.3%
Torres MJ. (1) / 15544603 / 2004 / x / x / x / S=48.6%
SP=91.3%
BAT in SPT negative: 41%
Torres MJ. (31) / 21812844 / 2011 / x / x / x / S= 52.7%
SP= 90%
Quinolones
Aranda A. (32) / 20722637 / 2011 / x / x / S=71.05%
S=60.5% to CIP
S=31.6% to MOX
S= 21% to LEV
SP=88%
Rouzaire P. (33) / 22041525 / 2012 / x / S=50%
BAT in SPT negative: 12%
Mayorga C. (34) / 23183272 / 2013 / x / S= 17.9% in light
S= 35.7% in dark
SP=90% in both
light and dark
NMBA
Kvedariene V. (35) / 16436139 / 2006 / x / x / S= 36.1%,
Up to 85.7% within 3 years.
SP=93.3%.
Leysen J. (36) / 21375539 / 2011 / x / x / x / S=80%
SP=96%
Monneret G. (37) / 11846462 / 2002 / x / x / x / S=54%,
SP=100%
Sudheer P.S. (38) / 15710010 / 2005 / x / x / x / CD 63: S= 79%,
CD203c: S= 36%
SP=100%
NSAID (Pyrazolones)
Gomez E. (39) / 19400910 / 2009 / x / x / S= 54.9%.
SP= 85.71%
BAT in SPT negative: 33.3%
Gamboa P. (40) / 12708979 / 2003 / x / x / x / S= 42.3%
SP=100%
BAT in SPT negative: 30%
Table 3 Food allergy
Table 3.1. Studies assessing the role of BAT in the diagnosis of food allergy
Author / PMID / Year / CD63 / CD203c / SPT / s-IgE / Diagnostic performance of BATPeanut
Ocmant (41) / 19549026 / 2009 / x / x / x / x / CD63
S=81.3%
Sp=95.4%
CD203c
S=89.5%
Sp=97.2%
Javaloyes (42) / 23397673 / 2012 / x / Peanut extract
S=92%
Sp=95%
rAra h 9
S=88%
Sp=100%
Glaumann(43) / 22126416 / 2012 / x / S=92%
Sp=77%
Santos (44) / 25065721 / 2014 / x / x / x / x / Primary population
S=98%
Sp=96%
Validation population
S=83%
Sp=100%
Hazelnut
Cucu (45) / 22406579 / 2012 / x / ND
Worm (46) / 19040466 / 2009 / x / ND
Peach
Gamboa (47)
Gamboa (48) / 19274924
17362252 / 2009
2007 / x / ND
Diaz-Perales (49) / 12642848 / 2003 / X / ND
Wheat
Carrocio (50) / 2318375 / 2013 / x / S=25%
Sp=73%
Carrocio (51) / 22825366 / 2012 / x / ND
Chinuki (52) / 22464646 / 2012 / X / ND
Tokuda (53) / 19240377 / 2009 / x / x / EtOH
S=83.3%
Sp=69.2%
Alkaline
S=83.7%
Sp=66.7%
r ω-5 gliadin
S=82.5%
Sp=63.4%
n ω-5 gliadin
S=85%
Sp=77.2%
Birch pollen associated food allergy
Ebo (54) / 15668987 / 2005 / x / x / x / AOS+ vs. AOS-
S=88%
Sp=75%
OAS+ vs. NA
S=100%
Sp=100%
Apple, celery and carrot
Erdmann(7) / 15713985 / 2005 / X / rMal d 1
S=75%
Sp=68%
rApi g 1
S=75%
Sp=77%
rDau c 1
S=65%
Sp=100%
Hazelnut
Erdmann (55) / 12752589 / 2003 / X / x / X / S=85%
Sp=80%
Celery
Erdmann (55) / 12752589 / 2003 / x / x / x / S=85%
Sp=80%
Carrot
Erdmann (55) / 12752589 / 2003 / x / x / x / S=85%
Sp=85%
Cow's milk
Sato (56) / 20523064 / 2010 / x / Cow's milk
S=89%
Sp=83%
Casein
S=67%
Sp=71%
Ciepela (57) / 21147615 / 2010 / x / ND
Egg
Sato (56) / 20523064 / 2010 / x / HEA+/HEA-
S=73%EW
Sp=62%EW
REA+/RAE-
S=77%EW
Sp=63%EW
HEA+/HEA-
S=80%OVM
Sp=73% OVM
REA+/RAE-
S=83%OVM
Sp=83%OVM
Ocmant (41) / 19549026 / 2009 / x / x / x / x / BAT (CD63)
S=77.4%
Sp=100%
BAT(CD203c)
S=62.5%
Sp=96.4%
Freshwater prawn
Ebo (58) / 18564641 / 2008 / x / S=100%
Sp=100%
10 foods (peanut, egg, cow's milk, goat's cheese, fish, crab, peas, soya, lentil, Brazil nut, almond)
Moneret-Vautrin (59) / 9988204 / 1999 / x / S=80%
Sp=100%
Table 3.2. Studies assessing the role of BAT in predicting the development of tolerance in food allergic children
Author / PMID / Year / CD63 / CD203c / SPT / s-IgE / Diagnostic performance of BATCow's milk
Ford (60) / 22819512 / 2013 / x / X / x / x / AUC ROC of
BAT =0.69
Rubio (61) / 20608919 / 2011 / x / x / x / S=91%
Sp=90%
AUC ROC = 0.866
Wanich (62) / 19348919 / 2009 / x / x / ND
Wheat
Nilsson (63) / 23816701 / 2013 / x / ND
Table 3.3. Studies using BAT to monitor the response to immunomodulatory treatments for food allergy
Intervention / Author / PMID / Year / CD63 / CD203c / Changes in BAT with treatmentPeanut
RIT / Wood (64) / 23265698 / 2013 / x / x / Increase in basophil reactivity at Week 16.
SLIT / Fleischer (65) / 23265698 / 2013 / x / x / Decrease in %CD63+ basophils with SLIT compared with placebo
Kim (66) / 21281959 / 2011 / x / Decrease in %CD63+ basophils after 12M of peanut SLIT (at 1 ng/ml and 10 ng/ml of peanut extract)
OIT / Thyagarajan(67) / 22805467 / 2012 / x / x /
- Decrease in basophil maximal reactivity to peanut extract (0.1-10,000ng/ml)
- 10-fold decrease basophil sensitivity to peanut extract
Jones (68) / 19577283 / 2009 / x / x / Decrease in %CD63+ basophils within 4M of peanut OIT
Omalizumab / Gernez (69) / 20975283 / 2011 / x / x / Basophil CD203c expression following stimulation with peanut allergen was significantly decreased after 4 and 8 weeks of omalizumab but returned to pretreatment levels after treatment cessation.
Cow’s milk
SLIT/OIT / Keet (70) / 22130425 / 2012 / x / x /
- Constitutive expression of CD203c increased at 20w, decreased below baseline at 80w (after 60w on maintenance) in all study arms and remained low in the POIT groups
- Constitutive expression of CD63 decreased at 80w in the SLIT/SLIT group
- No significant difference between groups
Egg
OIT / Vila (71) / 23682931 / 2013 / x / Decrease in egg-induced CD63 expression
Burks (72) / 22808958 / 2012 / x / x /
- Reduced egg-induced basophil activation in the actively treated group compared with placebo
- Patients that were successfully dessensitised at 10M showed reduced %CD63+ basophils at 0.1µg/ml of egg extract
- Patients that were successfully dessensitised at 22M showed reduced %CD63+ basophils at both concentrations of egg extract
- No difference in basophil activation between patients that passed or failed the OFC at 24M
Apple
OIT / Kopac (73) / 22070352 / 2012 / x / No difference in basophil activation at baseline and 8M between study arms.
Peanut, tree nuts, fish, shellfish
FAHF-2 / Patil (74) / 21794906 / 2011 / x / Reduced basophil activation at 6M
Table 4 Hymenoptera venom allergy
Table 4.1 Sensitivity and specificity of BAT, sIgE, SPT and DPT in insect venom allergy
Author / PMID / Year / CD63 / CD203c / SPT/IDT / sIgE / Clinical history vs. BAT
Sainte-Laudy J (75) / 1093112500/00/00 00.00 / 2000 / x / x / x / Sensitivity BAT: 100%
sIgE: 88%
Specificity BAT: 100%
Siegmund R(76) / 11112905 / 2000 / x / x / x / Not calculated (topic: BAT and IT)
Platz I(77) / 11815741 / 2001 / x / x / x / Sensitivity BAT: 90.9%, sIgE: 85.7%
Specificity BAT: 84.6%, sIgE: 76.9%
Binder M(78) / 12403934 / 2002 / x / x / x / Sensitivity BAT: 89.7%, sIgE: 92.3%
Specificity BAT: 100%, sIgE: 100%
Lambert C(79) / 12599177 / 2003 / x / x / x / Sensitivity BAT: 91% (releaser)
Data for sIgE not clearly mentioned.
Sturm GJ(12) / 15355471 / 2004 / x / x / x / Sensitivity BAT: 87.7%
sIgE: 91.2%
Specificity BAT: 86.7%
sIgE: 66.7%
Erdmann SM(80) / 15355470 / 2004 / x / x / x / Sensitivity BAT: 92%
sIgE: 76%
Specificity BAT: 80%
sIgE: 85%
Eberlein-König B(81) / 15160437 / 2004 / x / x / x / Concordance of sIgE and BAT: 57.1%
Brown SGA(82) / 15144473 / 2004 / x / x / x / Not calculated (topic: BAT and IT)
Kosnik M(8) / 16197472 / 2005 / x / x / x / Not calculated (topic: BAT and IT)
Eberlein-König B(83) / 16599242 / 2006 / x / x / x / Sensitivity BAT bee venom: 100%, sIgE: 91.7%
BAT wasp venom: 75%, sIgE: 97.4%
BAT bee and wasp venom: 100%, sIgE: 100%
Specificity: 100%
Eberlein-König B(84) / 16918511 / 2006 / x / x / x / x / Sensitivity BAT (CD203c): 97%
BAT (CD63): 89%
Specificity BAT (CD203c): 89%
BAT (CD63): 100%
Sainte-Laudy J (85) / 17659434 / 2007 / x / x / x / Sensitivity BAT: 100%
Ebo DG(86) / 17111386 / 2007 / x / x / x / Sensitivity BAT: 86.4%
sIgE: 86.4%
Specificity BAT: 100%
sIgE: 100%
Ebo DG(87) / 18088016 / 2007 / x / x / x / Not clearly calculated
Scherer K(88) / 18204278 / 2008 / x / x / x / Sensitivity BAT bee venom: 89.5%, sIgE 92.5
BAT wasp venom: 86.7%, sIgE 92.4%
Specificity BAT bee venom: 94.9%, sIgE 83.7%
Specificity BAT wasp venom: 97.2% , sIgE 93%
Sturm G(13) / 19243362 / 2009 / x / x / x / Not calculated (topic: technical issues)
Peternelj A(9) / 18270492 / 2008 / x / x / x / Sensitivity BAT: 90%, sIgE: 76%
PPV: BAT 79%; sIgE 73% (bee venom); BAT 86%; sIgE 59% (wasp venom); BAT 84%; sIgE 77% (both venoms)
Korosec P(10) / 19689457 / 2009 / x / x / x / BAT: 60% positive in patients with negative intradermal test
Kucera P(89) / 20461965 / 2010 / x / x / x / Not calculated (topic: BAT and IT)
Mikkelsen S(90) / 20158902 / 2010 / x / x / x / x / Not calculated (topic: BAT and IT)
Mertens M(91) / 20545702 / 2010 / x / x / x / Not calculated (topic: double sensitization and CCDs)
Ott H(92) / 21271515 / 2011 / x / x / x / Sensitivity BAT: 67%-75%; sIgE: 100%
Gonzalez-de-Olano D(93) / 21520404 / 2011 / x / x / x / Not calculated
Sturm G(14) / 21698247 / 2011 / x / x / x / Not calculated (topic: double sensitization)
Neis M(94) / 21861175 / 2011 / x / x / x / Not calculated (topic: BAT and IT)
Zitnic SE(95) / 22136583 / 2012 / x / x / x / Sensitivity BAT: 100%, sIgE: 100%
Specificity BAT: 52%, sIgE: 74%
Erzen R(96) / 22469017 / 2012 / x / x / x / Not calculated (topic: BAT and IT)
Eberlein B(16) / 22421265 / 2012 / x / x / x / Not calculated (topic: double sensitization and CCDs)
Celesnik N(97) / 23066930 / 2012 / x / x / x / Not calculated (topic: BAT and IT)
Bonadonna P(98) / 22676063 / 2012 / x / x / x / Not calculated (topic: mastocytosis)
Nullens S(99) / 23450838 / 2013 / x / x / x / x / Not calculated (topic: BAT and IT)
Ebo DG(100) / 23331567 / 2013 / x / x / x / Not calculated
Korosec P(11) / 23689117 / 2013 / x / x / x / BAT: 81% positive in patients with negative sIgE
Sturm GJ(15) / 24365141 / 2013 / x / x / x / Not calculated (topic: sensitized individuals)
Bidad K(101) / 24327387 / 2013 / x / x / x / x / Sensitivity BAT: 87%
Specificity BAT: 100%
(topic: BAT and IT, mastocytosis)
Celesnik N (102) / 24733549 / 2014 / x / x / Not calculated (topic: BAT and IT)
Table 4.2 BAT with insect venom recombinants
Author / PMID / Year / CD63 / CD203c / Recombinanttested
Seismann H (17) / 10931125 / 2010 / x / rVes v 1
Blank S (18) / 20348419 / 2010 / x / rApi m 5 and rVes v 3
Blank S(19) / 21658068 / 2011 / x / rApi m 10
Balzer L (20) / 25329342 / 2014 / x / rVes v 1, 2, 3 and 5, rVes v 5 BAT showed 100% specificity and 82% sensitivity
Table 5 Inhalant Allergens
Sensitivity and specificity of BAT, s-IgE, SPT and IDT in inhalant allergy
Author / PMID / Year / CD63 / CD203c / SPT / s-IgE / BAT vs. clinical historyPâris-Köhler A(103) / 10669856 / 2000 / x / x / X / Sensitivity BAT: 91%, IgE-ab 76%
Specificity BAT: 100%, IgE-ab 100%
Sanz ML(104) / 11467990 / 2001 / x / x / x / Sensitivity BAT: 93%
Specificity BAT: 98%
Saporta M(105) / 11350309 / 2001 / x / x / x / Not calculated (topic: BAT and stability during pollen season)
Hauswirth A(22) / 12110828 / 2002 / x / x / x / x / Not calculated (topic: BAT and recombinant allergens)
Nopp A(106) / 16436137 / 2006 / x / x / x / Concordance of % sIgE-ab and BAT: 72%
SPT and BAT: 50%
Nasal provocation and BAT: 54%
Ocmant A(21) / 17275019 / 2007 / x / x / x / x / Sensitivity BAT (CD63): 100%
Specificity (CD63) BAT: 95%
Sensitivity BAT (CD203c): 95%
Specificity (CD203c) BAT: 95%
Nopp A(107) / 19220221 / 2009 / x / x / x / Not calculated (topic: BAT and AIT)
Ceuppens JL(108) / 20085600 / 2009 / x / x / x / Not calculated (topic: BAT and AIT)
Johansson SGO(109) / 19393000 / 2009 / x / x / Not calculated (topic: BAT and omalizumab)
Lalek N(110) / 20528883 / 2010 / x / x / Not calculated (topic: BAT and AIT)
Dahlen B / 21518044 / 2011 / x / x / x / Concordance of bronchial allergen challenge and BAT: 88%
Zidarn M(24) / 22093044 / 2011 / x / x / x / Concordance of %IgE-ab and BAT: 75-84%
Özdemir SK(111) / 22185730 / 2011 / x / x / x / Sensitivity BAT: 95%
Specificity BAT: 95%
Nopp A(112) / 23257907 / 2013 / x / x / x / Concordance of nasal allergen challenge and BAT: 92%
Schmid JM (25) / 2014 / x / x / x / Basophil sensitivity three weeks after treatment start predicts clinical efficacy of SCIT
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