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M.R. Yacoub1, E. Savi2, S.E Burastero1, S. Dal Farra1, C. Mason1, S. Pecora3,
G. Colombo1
1 Allergy and Immunology Unit, San Raffaele Scientific Institute, Milan, Italy - E-mail: yacoub.monarita@hsr.it
2Allergy Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy
3ALK-Abellò A/S, Hørsholm, DK
Omega-5 gliadin anaphylaxis: an integrated diagnostic
approach
Summary
We report the case of a 62-year old man who presented a wheat-dependent, exercise-
induced anaphylaxis (WDEIA). The case illustrates the usefulness of skin prick test not
only with wheat extract, but also with native gliadin extract. Moreover we confirm
the value of recombinant IgE dosage with rTri a 19 omega-5 gliadin in the diagnostic
pathway of this condition.
Key words
Anaphylaxis, exercise-induced
anaphylaxis, omega-5-gliadin,
recombinant allergens, wheat
Corresponding author
Mona-Rita Yacoub,
San Raffaele Scientific Institute,
Via Olgettina, 60
20132 Milan (Italy)
E-mail: yacoub.monarita@hsr.it
Wheat-dependent exercise-induced anaphylaxis (WDEIA)
is a well described life-threatening clinical presentation of
food allergy, that occurs when a wheat-sensitized subject
practises exercise in the few hours following ingestion of
foods containing wheat proteins. Correlation between the
amount of wheat and the intensity of exercise with the
severity of the hypersensitivity reaction is unclear. Diagnos-
tic pathway consists of an accurate clinical history including
trigger factors (besides exercise, also aspirin and cold may
play a role as cofactors), skin prick test (SPT), and IgE
dosage for allergenic extracts and specific allergenic mole-
cules.
We report a case of WDEIA in a 62-year-old, non-smoker
man in good health, who had been suffering of recurrent ur-
ticaria, in the absence of known trigger factors, in the previ-
ous two years. He used to successfully treat his symptoms
with an antihistaminic drug on demand. He reported also
the first episode of acute generalized urticaria, lip angioede-
ma and hypotension (Systolic blood pressure: 50 mm Hg,
diastolic blood pressure not measurable), four months before
being visited at our clinic. This episode required systemic
corticosteroids and antihistaminic therapy in the Emer-
gency Unit. These symptoms occurred while taking a walk
in a wood a few minutes after Easter lunch, consisting of
pasta, cheese, eggs, beef, Cremona’s mustard (preserve made
from candied fruits in grape must or sugar with mustard),
milk chocolate, cake with candied fruit, red and sparkling
wine. One month later, he reported a similar episode while
he was dancing. Also on this occasion, he had just ended a
lunch consisting of salted fritter (made by wheat, milk, yeast
and olive oil), French fries, pork, and white wine. Also this
episode required systemic corticosteroids, antihistaminic
therapy and Ringer's lactate solution in the Emergency
Unit. In this occasion he was discharged with the diagnosis
of: ’’neurologically mediated syncope’’ and he was prescribed
epinephrine auto-injector on demand. Before being visited
Eur Ann Allergy Clin Immunol VOL43, N 3, 92-94, 2011
C A S E R E P O R T
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93
Omega-5 gliadin anaphylaxis:an integrated diagnostic approach
at our clinic, the patient had already performed SPT with
common food allergens, which yielded negative results: total
IgE were 122 kU/L (normal value <100 in this laboratory);
serum specific IgE for a standard group of food allergens,
which scored negative, with the exception of a low value for
whole wheat (ImmunoCAP® Phadia: 0.22 kU/L), at that
time not considered clinically relevant. During the evalua-
tion at our Hospital, SPT with commercial food allergens
extracts (ALK Abellò A/S, Hørsholm, DK) including
whole wheat were performed and resulted positive only for
gliadin, that elicited a 9 mm diameter wheal. The determi-
nation of specific IgE for omega-5 gliadin (rTri a 19
omega-5 gliadin) was assessed both with ImmunoCAP-
ISAC (Immuno Solidphase Allergen Chip,) and with Im-
munoCAP (Phadia), and scored respectively 5,8 ISAC
Standardized Units (reported normal value < 0.3 ISU) ver-
sus 20.5KU/L (reported normal value <0.10 kU/L). These
last results, together with the clinical history, allowed to
confirm the diagnosis of wheat-dependent exercise-induced
anaphylaxis, mediated by sensitization to omega-5 gliadin.
After the diagnosis the patient returned to practise his
leisure activities (dancing and trekking) and he did not ex-
perience new allergic reactions by avoiding the ingestion of
wheat.
In order to justify the discrepancy between SPT results, im-
munoblotting was performed with natural wheat and gliadin
extracts used for SPT (Alk Abello, Madrid, Spain - Figure
1). It demonstrates a low content of omega-5 gliadin in the
whole wheat commercial extract, and also a different aller-
gen content in the two extracts; moreover, to explain nega-
tive SPT with whole wheat and positive with gliadin, we
performed a RAST inhibition of patient serum with com-
mercially whole wheat and gliadin extracts (ALK-Abellò
A/S, Hørsholm, DK), which confirmed the low content of
omega-5 gliadin in whole wheat extract for SPT (Figure 2).
In conclusion WDEIA is a well-described clinical entity,
that usually affects young adults and adolescents2. Our case
emphasize the role of a multifaceted diagnostic approach,
combining different in vivo and in vitro tools. In particular,
Figure 2 - Inhibition of IgE binding to Tri a 19 (omega-5-gliadin
allergen component) by gliadin extract and wheat (Triticum aesti-
vum) extract (ALK Abellò, 1/20 W/V), as measured by Immuno-
CAP. One volume of serum from patient C.P. was pre-incubated
with 1.5 volumes of either saline solution or allergen extracts for
prick testing at different concentrations (the latter were obtained
by dilutions in saline, indicated on the x axis) and specific IgE bin-
ding was measured. Results are expressed as percent inhibition (on
the y axis) versus serum diluted with saline.
Figure 1 - Different omega-5-gliadin content in wheat versus glia-
din extract. Gliadin extract (left panel, lanes 1, 2, 3) and whole
wheat extract (right panel, lanes 1', 2', 3') for skin prick testing
(ALK Abellò, Madrid, Spain) (1/20 W/V) were run in non-redu-
cing conditions in 12% sodium dodecyl sulphate (SDS) polyacryla-
mide (PAGE) gel electrophoresis. Proteins were transferred to a
nitrocellulose membrane (Hybond ECL, Amersham Pharmacia
Biotech) and reacted onto single strips with 1:5 diluted sera from
one non allergic control individual (lanes 1 and 1') and subsequen-
tly with probe (HRP-conjugated rabbit anti-human IgE, DAKO),
with probe only (lanes 2 and 2') and with a pool of sera from pa-
tients with wheat allergy (level of IgE toTriticum aestivum: RAST
class 3), which served as positive control, followed by the anti-IgE
probe (lanes 3 and 3'). Bound antibodies were revealed by enhan-
ced chemiluminescence autoradiography (ECL, Amersham Phar-
macia Biotech). Molecular weight (MW) markers (Bio-Rad, Ri-
chmond CA, USA) were run in a different strip and reported vi-
sually with a pencil. The expected migration patter of known glia-
dins is reported on the right.
08-Yacoub:Fumagalli 18-05-2011 9:06 Pagina 93
94 M.R. Yacoub, E. Savi, S.E Burastero, et al.
our case underlines: 1) the importance of performing SPT
with gliadin extract to detect omega-5 gliadin sensitization.
This could overcome the lack of standardization of the dif-
ferent commercial extracts due to the technical difficulties in
obtaining the different allergenic molecules, especially in
whole extracts; 2) the importance to use a 0.10 kU/L
threshold value for specific IgE level (rather than 0.35
which is still used in some laboratories) and in WDEIA the
possible clinical relevance of low specific IgE level for
wheat; 3) the diagnostic value of specific IgE dosage for re-
combinant molecules, and the better sensitivity of CAP over
ISAC for omega-5 gliadin. Finally, WDEIA should be con-
sidered not only in young people but also in elderly subjects,
even in the absence of any previous IgE-dependent allergic
clinical history.
References
1. Inomata N. Wheat allergy. Curr Opin Allergy Clin Immunol
2009; 9:238–43.
2. Morita E, Kunie K, Matsuo H. Food-dependent exercise-induced
anaphylaxis. J Dermatol Sci 2007; 47:109–17.
3. Palosuo K. Update on wheat hypersensitivity. Curr Opin Allergy
Clin Immunol 2003; 3:205–9.
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