What diagnosis atopy

WHAT YOU SOULD HAVE READ BUT ………………… 2018
Diagnosis of atopy
Attilio Boner
University of Verona, Italy
attilio.boner@univr.it

Clinical aspects
Monosensitization
Polisensitization

Staphylococcus aureus enterotoxin sensitization is
associated with allergic poly-sensitization
and allergic multimorbidity in adolescents
M Sørensen, Allergy 2017;72:1548–1555
41.7%
% adolescents with
sensitization to at least one
food or inhalant allergen
50 –
40 –
30 –
20 –
10 –
00
 A school-based cohort
of 868 adolescents.
 Nasal S. aureus carriage,
serum total IgE and
specific IgE to SEs,
food and inhalant
allergens.

26.2%
% adolescents with
sensitization to at least
one Staphylococcus
aureus enterotoxin
50 –
40 –
30 –
20 –
10 –
00
of 868 adolescents.
serum total IgE and
food and inhalant
allergens.

26.2%
% adolescents with
sensitization to at least
one Staphylococcus
aureus enterotoxin
50 –
40 –
30 –
20 –
10 –
00
of 868 adolescents.
serum total IgE and
food and inhalant
allergens.
SE sensitization, but not
S. aureus carriage, was
associated with poly-
sensitization to food
and inhalant allergens.

• SE-sensitized participants had
higher median specific IgE
to inhalant allergens
(41.4 kUA/L) compared to
non-SE-sensitized participants
(18.0 kUA/L, P=0.004),
but not to food allergens.
 A school-based cohort of
868 adolescents.
serum total IgE and
and food and inhalant
allergens.

• SE-sensitized participants had
higher median specific IgE
to inhalant allergens
(41.4 kUA/L) compared to
non-SE-sensitized participants
(18.0 kUA/L, P=0.004),
but not to food allergens.
 A school-based cohort of
868 adolescents.
serum total IgE and
and food and inhalant
allergens.
Sensitization to SEs
may play a role in the
development of allergen
poly-sensitization
and allergic
multimorbidity.

 In this large cross-sectional study of late adolescents we found that SE
sensitization was significantly associated with allergic multimorbidity.
 Moreover, SE sensitization was significantly associated with poly-
sensitization to both food and inhalant allergens, and specific IgE values
to inhalant allergens were higher in the SE-sensitized group.
 Staphylococcus aureus carriage was not associated with inhalant allergen
poly-sensitization when SE-sensitized participants were excluded from
the analysis. This indicates that SE sensitization is more likely to affect
poly-sensitization than S. aureus carriage per se.

 We have previously reported (in the same study) associations between
S. aureus carriage and severe asthma, eczema, severe eczema, severe
allergic rhinitis, and multimorbidity.
 Our data indicate that S. aureus carriage may affect the severity
of allergic diseases in adolescents, rather than inducing polyclonal
sensitization.

Lip b 1 is a novel allergenic protein isolated from
the booklouse, Liposcelis bostrychophila
O Ishibashi, Allergy 2017;72:918-926
• Booklice, alternatively called psocids, are household insect pests
belonging to the order Psocoptera. Members of Psocoptera are
distributed in geographical regions ranging from tropical to subarctic
zones. Booklice are brownish, soft-bodied insects that are 1.0–1.3-mm
long when fully grown.
• Booklice do not bite humans or animals, transmit diseases, or damage
food or fabric.
• Booklice account for the majority of detectable insects in house dust,
presenting at a frequency of ~90% in dust samples.

• We previously demonstrated that booklouse-specific IgE antibodies
were detected in sera from 22% of Japanese asthmatic patients.
• A study from India also showed that 20% of patients with a
nasobronchial allergy exhibits a strong skin sensitivity to Psocoptera spp.
• These studies strongly suggest that L. bostrychophila detected in house
dust could be a potent indoor allergen.

• We previously demonstrated that booklouse-specific IgE antibodies
were detected in sera from 22% of Japanese asthmatic patients.
• A study from India also showed that 20% of patients with a
nasobronchial allergy exhibits a strong skin sensitivity to Psocoptera spp.
• These studies strongly suggest that L. bostrychophila detected in house
dust could be a potent indoor allergen.
Lip b 1 is a novel protein possibly
causing booklouse allergy

A new allergen family involved in pollen food-associated
syndrome: Snakin/gibberellin-regulated proteins.
Sénéchal H, J Allergy Clin Immunol. 2018 Jan;141(1):411-414.e4.
•Around the Mediterranean basin, Cupressaceae pollen
is considered as the primary cause of respiratory
allergies with symptoms of rhinoconjunctivitis,
chronic cough, and asthma.
•The pollinosis can be severe including infectious complications,
partly due to winter pathologies occurring within cypress pollinating period.
•In Southern France, a pollen food-associated syndrome
(PFAS) was described involving cypress pollen and
peach and/or citrus sensitizations inducing mainly
oral syndrome but also urticaria and angioedema.

•Up to now, the cross-reactive allergen at the basis
of this syndrome has not yet been unraveled.
•Besides the 4 groups of allergens already described in the various
Cupressaceae species, an as yet unidentified basic allergen of
14 kDa (BP14), overexpressed in Cupressus sempervirens pollen
and different from a lipid transfer protein, was found to sensitize
37% of cypress pollen allergic patients (CPAPs) in Southern France.
•The BP14 IgE epitopes are not related to cross-reactive carbohydrate
determinants and are heat resistant but destroyed under reducing
conditions.

conditions.
2 overlapping peptides of the gibberellin-regulated protein
(GRP) peamaclein (Pru p 7 from peach) were found:
R.CLKYCGICCEK.C and K.YCGICCEK.C.

14 kDa (BP14)*, overexpressed in Cupressus sempervirens pollen
conditions.
*Gibberellins (GAs) are plant hormones that regulate growth and
influence various developmental processes, including stem
elongation, germination, dormancy, flowering,
sex expression, enzyme induction, and leaf
and fruit senescence

conditions.
Furthermore, 1 very similar peptide of the GRP of
Theobroma cacao was identified:
R.CLKYCGICCK.K

•BP14 allergen from C sempervirens is cross-reactive with a member of the
snakin/GRP protein family while also displaying some specific IgE epitopes.
•Snakin/GRPs are involved in plant
development such as pollen maturation,
responses to biotic or abiotic stress,
hormone crosstalk, and redox homeostasis.
•They are small cationic polypeptides
described in flowers, vegetables,
and fruits, with 12 highly conserved
cysteins and with antimicrobial activity.

•4 snakin/GRPs (gibberellin-regulated protein*) from fruits were shown to be
allergens (www.allergen.org) :
Pru p 7 in peach,
Pun g 7 in pomegranate,
Pru m 7 in Japanese apricot
Cit s 7 in sweet orange,
•Because Pru p 7 shares more than 80% sequence identity with snakin-1 and
more than 95% with other fruit GRP allergens, BP14 in Cupressus
sempervirens pollen should be considered as the cross-reactive allergen in
the 2 documented PFAS involving peach and/or citrus.

•4 snakin/GRPs (gibberellin-regulated protein*) from fruits were shown to be
allergens (www.allergen.org) :
Pru p 7 in peach,
Pun g 7 in pomegranate,
Pru m 7 in Japanese apricot
Cit s 7 in sweet orange,
•Because Pru p 7 shares more than 80% sequence identity with snakin-1 and
more than 95% with other fruit GRP allergens, BP14 in Cupressus
sempervirens pollen should be considered as the cross-reactive allergen in
the 2 documented PFAS involving peach and/or citrus.
Snakin/GRP sensitization was reported to
be clinically associated with eyelid edema,
systemic reaction, or food-dependent exercise-induced
anaphylaxis.

•Preliminary experiments showed that patients allergic to cypress
pollen and citrus expressed IgE against cypress pollen BP14
cross-reactive with a cationic 12-kDa allergen from grapefruit.
•Therefore, snakin/GRP may represent a new diagnostic
marker of pollen food-associated syndrome (PFAS)
in addition to other allergens
such as Bet v 1–like proteins
involved in the well-studied
birch/apple syndrome.

Whether specific allergenic immunotherapy using
a BP14- containing cypress pollen extract can reduce
the food-related symptoms remains unknown for the moment
and would deserve more investigations.
With regard to allergy to Cupressaceae pollen, it has been reported that a
specific allergenic immunotherapy performed with a Japanese cedar pollen
extract led to a decrease in basophile activation to tomato
in a patient with a cedar/tomato syndrome.

Approach to hypersensitivity reactions
from intravenous iron preparations
CA Morales Mateluna, Allergy 2017;72:827-830
• Oral iron is the treatment of choice for iron deficiency anemia.
• However, this form of therapy might not be adequate for some patients
for a variety of reasons (intolerance, malabsorption, compliance, etc.).
• Parenteral iron was introduced in the 1930s.
• Due to frequent toxic reactions, intravenous iron compounds encased
in carbohydrate shells were developed, eventually leading to the
introduction of an iron preparation encased in a dextran shell in the
1950s.

Approach to hypersensitivity reactions from
intravenous iron preparations
• Compared with earlier preparations, dextran iron caused fewer adverse
reactions, but a meta-analysis published in 2002 estimated the incidence
of life-threatening HSRs at 0.61%.
• These reactions have been demonstrated to be caused by preexisting
IgG and IgM antibodies to dextran in some patients.
• The introduction of nondextran iron preparations (NDIPs) has led to a
further decrease in HSRs, now considered rare events.
• Despite the very low rate of HSRs to NDIPs, these drugs are considered
dangerous and re-administration after HSRs is strongly discouraged.
• Rare fatalities associated with NDIPs have been anecdotically reported.

31 patients with
mild to severe
reactions
to intravenous iron
preparations.
SPTs and basophil activation tests
(BATs) were negative
in all patients tested

31 patients with
mild to severe
reactions
to intravenous iron
preparations.
 controlled re-administration (CRA)
were performed in 15 patients:
• 12 patients tolerated the
procedure, including 3 with
a previous grade IV HSR.
• 2 patients developed urticaria
• 1 developed urticaria and dyspnea.

31 patients with
mild to severe
reactions
to intravenous iron
preparations.
The
pathophysiology
of HSRs to
IVIPs remains
currently unclear.
SPTs and BATs
provided no
additional
information.

31 patients with
mild to severe
reactions
to intravenous iron
preparations.
However,
in appropriate
situations,
CRA under
surveillance
can be safely
performed in
most patients.

• Local allergy
• Hiddeen allergy

Clinical History
Anamnesi per la diagnosi

Skin prick tests and specific IgE in 10-year-old children:
Agreement and association with allergic diseases.
Chauveau A, Allergy. 2017;72(9):1365-1373.
Background:
•Accurate assessment of atopic sensitization is pivotal to clinical practice
and research.
•Skin prick test (SPT) and specific IgE (sIgE) are often used
interchangeably.
•Some studies have suggested a disagreement between these two
methods, and little is known about their association with allergic diseases.
•The aims of our study were to evaluate agreement between SPT and sIgE,
and to compare their association with allergic diseases
in 10-year-old children.

INTRODUCTION
•Skin prick testing (SPT) and measurement of specific IgE (sIgE) are important
tools for diagnosing atopic sensitization, but no gold standard exists.
•In clinical practice as well as in allergy research, both tests are often used
interchangeably.
•While a few studies have shown some discordance between these two methods in
adults,2,3 most studies were performed in the hospital setting, whereas far fewer
studies have compared SPTs and sIgE head-to-head in childhood,4,5 and fewer still
have done so in unselected birth cohorts.5
2. De Vos G. Skin testing versus serum-specific IgE testing: which is better for diagnosing aeroallergen
sensitization and predicting clinical allergy? Curr Allergy Asthma Rep. 2014;14:430.
3. Bousquet P-J. Assessing skin prick testsreliability in ECRHS-I. Allergy. 2008;63:341-346.
4. Schoos A-MM, Disagreement between skin prick test and specific IgE in young children. Allergy.
2015;70:41-48.
5. De Vos G, Discordance between aeroallergen specific serum IgE and skin testing in children younger
than 4 years. Ann Allergy Asthma Immunol. 2013;110:438-443.

INTRODUCTION
•The results of a substudy on atopic sensitization in French children from the
PASTURE (Protection against Allergy: STUdy in Rural Environment) cohort
suggested disagreement between SPT and sIgE in the first 6 years of life.6
•The discordance between these two tests raises the question as to whether one
test method is better associated with allergic diseases than the other.
•Allergic rhinitis is known to be well correlated with both tests,7 but little is known
about other allergic diseases,8 especially in childhood.
6. Chauveau A, Disagreement between skin prick tests and specific IgE in early childhood. Int Arch
Allergy Immunol. 2016;170:69-74.
7. Droste JH, Association of skin test reactivity, specific IgE, total IgE, and eosinophils
with nasal symptoms in a community-based population study. The Dutch ECRHS Group. J Allergy Clin
Immunol. 1996;97:922-932.
8. Kjaer HF, The prevalence of allergic diseases in an unselected group of 6-year-old
children. The DARC birth cohort study. Pediatr Allergy Immunol.2008;19:737-745.

SPTs, sIgE measurements, and
assessment of allergic diseases
in 529 children aged 10 years in
the Protection against Allergy:
STUdy in Rural Environments
(PASTURE) cohort.
The agreement between SPT
and sIgE assessed by Cohen’s
kappa coefficient with different
cutoff values.
•The highest agreement (k=0.44) was
found with a cutoff value of 3 and 5
mm for SPT, and 3.5 IU/mL for sIgE.
•For asthma and hay fever, SPT
(cutoff value at 3 mm) had a
significantly higher specificity (true -)
(76.5%) (P<.0001) than sIgE (57.4%)
(cutoff value at 0.35 IU/mL)

(PASTURE) cohort.
cutoff values.
Agreement between SPT
and sIgE was globally
weak, with j coefficient
values ranging from 0.01 to
0.44 for any allergen .
The highest j value was
found with a cutoff value
at 3 mm for SPT and
0.7 or 3.5 IU/mL for sIgE.
•The highest agreement (k=0.44) was
found with a cutoff value of 3 and 5
mm for SPT, and 3.5 IU/mL for sIgE.
•For asthma and hay fever, SPT
(cutoff value at 3 mm) had a
significantly higher specificity (true -)
(76.5%) (P<.0001) than sIgE (57.4%)
(cutoff value at 0.35 IU/mL)

(PASTURE) cohort.
cutoff values.
•sIgE had a significantly higher
sensitivity (true +) than SPT for at
least one allergic disease (P=0.0164)
and for AD (P=0.0196),
•but the sensitivity of both test was
not significantly different for
Asthma and Hay fever (P=0.1088).

(PASTURE) cohort.
cutoff values.
•sIgE had a significantly higher
sensitivity (true +) than SPT for at
least one allergic disease (P=0.0164)
and for AD (P=0.0196),
•but the sensitivity of both test was
not significantly different for
Asthma and Hay fever (P=0.1088).
These findings show
that the choice of the
cutoff value for sIgE
has an important
impact on diagnostic
performance.

•The combined results of both tests
(SPT≥3 mm and/or sIgE≥0.35 IU/mL)
allow to have a significantly higher
sensitivity (true +)
(compared to SPT alone: P=<0.0001 for
at least one allergic disease;
compared to sIgE alone: P=0.0253 for
at least one allergic disease; but a
significantly lower specificity (true -)
( P<0.0001), regardless of the
allergic diseases.
(PASTURE) cohort.
cutoff values.

Children with atopic sensitization who would have been missed if only one
testing method would have been performed
Using SPT≥3 mm and/or sIgE≥0.35 IU/mL as the reference, 281 (53%)
children were considered to have atopic sensitization.
Among these, 127 (45.2%) would have been missed
(considered as not having atopic sensitization)
if only SPT had been performed,
vs
34 (12.1%) if sIgE alone had been performed.
sIgE

Children with atopic sensitization who would have been missed if only one
testing method would have been performed
Using SPT≥3 mm and/or sIgE≥0.35 IU/mL as the reference, 281 (53%)
children were considered to have atopic sensitization.
Among these, 127 (45.2%) would have been missed
(considered as not having atopic sensitization)
if only SPT had been performed,
vs
34 (12.1%) if sIgE alone had been performed.
sIgE
The disagreement between both tests leads one to wonder
whether one test has better association
with allergic diseases than the other.

DISCUSSION
•Our data show that there is only a moderate agreement between SPTs and
sIgE in a non selected cohort of 10-year-old children, irrespective of the
cutoff values used for each test.
•We found that SPTs, with a cutoff value of 3 mm, had a significantly higher
specificity for all allergic diseases than sIgE at a cutoff value of 0.35 IU/mL
but a significantly lower sensitivity for at least one allergic disease.
•The agreement between SPTs and sIgE was particularly poor for cat, do,
alternaria and grass pollen.

DISCUSSION
The choice of the method for each test may have repercussions
on the results.
Regarding the method chosen for SPT, Masse et al.15
found that the Stallerpoint device is less sensitive
than the ALK lancet or IV needle, but that the
90° clockwise rotation improves the sensitivity
of this technique.
Masse MS, Comparison of five techniques of skin prick tests used routinely in Europe. Allergy.
2011;66:1415-1419.

DISCUSSION
However, this technique was described by Buyuktiryaki et al.16 to be reliable,
tolerable, and comparable with the ALK lancet technique.
As reported in the EAACI position paper on skin prick testing,17 the protein
and antigen content can differ from one commercial SPT solution to another.
16. Buyuktiryaki B, Optimizing the use of a skin prick test device on children.
Int Arch Allergy Immunol. 2013;162:65-70.
17. Van Kampen V, EAACI position paper: skin prick testing in the diagnosis of occupational
type I allergies. Allergy. 2013;68:580-584.

DISCUSSION
Regarding the method chosen for sIgE, Wood et al.18 showed
some differences in sIgE results according to the method of assay.
However, Herzum et al.11 found that the Allergy Screen Test Panel yields
reliable results in the detection of allergic sensitization to common allergens.
Wood RA, Accuracy of IgE antibody laboratory results. Ann Allergy Asthma Immunol. 2007;
99:34-41.
11. Herzum I, Diagnostic and analytical performance of a screening panel for allergy. Clin Chem
Lab Med. 2005;43:963-966.

DISCUSSION
In our study, as in the PACT study,19 the association between each testing
method and allergic diseases did not differ.
The best diagnostic accuracy was for asthma, hay fever, and food allergy.
Nonetheless, the results obtained for food allergy must be interpreted
with caution because the prevalence of food allergy was very low and no
objective tests were performed to confirm food allergy.
19. Rø AD, The predictive value of allergen skin prick tests and IgE tests at pre-school age:
the PACT study. Pediatr Allergy Immunol. 2014;25:691-698.

DISCUSSION
In the study by Simpson et al.,20 the pattern of IgE responses
also appeared to be associated with current asthma and hay fever,
but not eczema.
In a study of a cohort at risk of atopy,21 sensitization, as detected by SPT
and sIgE at 13 years of age, was significantly associated with asthma, but
not with eczema.
20. Simpson A, Patterns of IgE responses to multiple allergen components and clinical
symptoms at age 11 years. J Allergy Clin Immunol. 2015;136:1224-1231.
21. Schoos A-MM, Atopic endotype in childhood. J Allergy Clin Immunol. 2016;137:844-851.

DISCUSSION
In the study by Simpson et al.,20 the pattern of IgE responses
also appeared to be associated with current asthma and hay fever,
but not eczema.
In a study of a cohort at risk of atopy,21 sensitization, as detected by SPT
and sIgE at 13 years of age, was significantly associated with asthma, but
not with eczema.
20. Simpson A, Patterns of IgE responses to multiple allergen components and clinical
symptoms at age 11 years. J Allergy Clin Immunol. 2015;136:1224-1231.
The diagnostic accuracy for AD is poor, probably because
the pathophysiology of AD only partially involves
an IgE-related mechanism.

DISCUSSION
In populations of food-allergic subjects, Soares-Weiser et al.22 reported
that SPT and sIgE were both sensitive, but not specific.
In the DARC birth cohort,8 SPTs were better correlated with a diagnosis
of allergic disease than sIgE.
22. Soares-Weiser K, The diagnosis of food allergy: a systematic review and meta-analysis.
Allergy. 2014;69:76-86.
8. Kjaer HF, The prevalence of allergic diseases in an unselected group of 6-year-old
children. The DARC birth cohort study. Pediatr Allergy Immunol.2008;19:737-745.

DISCUSSION
It has also been suggested that SPT and sIgE may be associated with
specific and different allergic diseases.23
23. Tollerud DJ, Asthma, hay fever, and phlegm production associated with distinct patterns
of allergy skin test reactivity, eosinophilia, and serum IgE levels. The Normative Aging Study.
Am Rev Respir Dis. 1991;144:776-781.

DISCUSSION
In a Norwegian study26 that compared sIgE measurement and
SPT in 2-year-old children, both tests yielded different results and
were not similar for the detection of atopic sensitization.
The authors concluded that both tests actually reflected distinct aspects of
the IgE-related immune response.
26. Rø AD, Agreement of specific IgE and skin prick test in an unselected cohort of two-year-
old children. Eur J Pediatr. 2012;171:479-484.

DISCUSSION
Schoos et al.4 also suggested that the immune response is different in the
skin and in the blood.
In their recent study, 21 Schoos et al. highlight the dilemma when trying to
define an atopic child. According to these suggestions, it would be
interesting to compare the immune responses (eg, cytokine profiles)
between children with positive SPT and those with positive sIgE.
4. Schoos A-MM, Disagreement between skin prick test and specific IgE in young children.
Allergy. 2015;70:41-48.

Comparison between skin prick test and serum
immunoglobulin E by CAP system to inhalant allergens
Young-Hee Nam, Ann Allergy Asthma Immunol 2017;118:608-613
Background
• Skin prick tests (SPTs) and measurements of serum specific
immunoglobulin E (sIgE) antibodies are the most commonly used
diagnostic tools for confirming sensitization.
• However, disagreement between the tests has been observed.
Objective
• To compare SPT and the CAP system for diagnosis of sensitization to
common inhalant allergens.

% agreement between
the SPT and sIgE level
75.3%
 2.635 patients 10
to 90 years old who
underwent analyses
by SPT and CAP from
June 2011 through
May 2016.
 The 2 test results
compared for 17
inhalant allergens.
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00 –

% agreement between
the SPT and sIgE level
75.3%
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00 –
Overall agreement was
moderate (κ = 0.59),
with strong agreement
for house dust mites
and birch (κ > 0.7) and
weak agreement for
dog (κ < 0.3)
 2.635 patients 10
to 90 years old who
underwent analyses
by SPT and CAP from
June 2011 through
May 2016.
 The 2 test results
compared for 17
inhalant allergens.

Conclusion
• There was a discrepancy between SPT and CAP for diagnosing allergic
sensitization among inhalant allergens.
• The allergic sensitization and correlation between the tests decreased
with age.
• Cautious interpretation of the clinical relevance of allergen sensitization
based on SPT and CAP results is required, especially in older patients.

• Total IgE
• IgE specifiche
vs SPTs
• IgG4

Growth curves of “normal” serum total IgE levels
throughout childhood: A quantile analysis in a birth cohort
C Sacco, PAI 2017;28:525-534
• Overall, 1113 of 1314
children were included
in this analysis.
• Of these, 469 were
“never atopic” and
644 atopic.
 German Multicentre Allergy
Study (MAS), a birth cohort
with 1314 recruited newborns,
began in 1990 and examined the
participants until age 20 years.
 Total IgE levels in children
without atopic sensitization.
 Participants were classified
as “never atopic” if all their
available serum samples had
negative response
(cutoff: <0.35 kUA/L) for
s-IgE to the 9 common
foodborne and airborne
allergenic.

C Sacco, PAI 2017;28:525-534
Quantile trajectories of predicted log-transformed
t-IgE levels (kU/L) by age estimated in the
population of “never atopic” subjects (n=466)
negative response
allergenic.

C Sacco, PAI 2017;28:525-534
Quantile trajectories of predicted log-transformed
t-IgE levels (kU/L) by age estimated in the
population of “never atopic” subjects (n=466)
negative response
allergenic.
Quantile trajectories
of t-IgE levels in
“never atopic” subjects
were stable from
5 years of age,
increased to a plateau
at age 10-13 years,
and decreased slightly
afterward.

C Sacco, PAI 2017;28:525-534
• The trajectory of t-IgE levels
can be elaborated since age
5 years in non-atopic children.
• A child whose t-IgE levels are
consistently higher than those
predicted by his/her growth
curve may have developed
atopic sensitization.
negative response
allergenic.
*
*
*
******

Component resolved Diagnosis
Pollens

Poaceae pollen as the leading aeroallergen worldwide:
A review. H García-Mozo, Allergy 2017;72:1849–1858
• The Poaceae family comprises
over 12 000 wind-pollinated
species, which release large
amounts of pollen into the
atmosphere.
• Poaceae pollen is currently
regarded as the leading airborne
biological pollutant and the chief
cause of pollen allergy worldwide.
• In Poaceae, there is a
considerable degree of cross-
reactivity between many species.
• The additional influence of urban
pollution may prompt a more
severe immunological response.
Poaceae pollen grain
Average size: 35 × 40 μm

• The term “grasses” is traditionally applied
to herbaceous species belonging to the Poaceae family.
• This botanical family includes 12 000 species classified into 771 grass
genera belonging to 12 subfamilies (Anomochlooideae, Aristidoideae,
Arundinoideae, Bambusoideae, Chloridoideae, Danthonioideae,
Micraioideae, Oryzoideae, Panicoideae, Pharoideae, Puelioideae, and
Pooideae).
• This group includes a number of major crop species
(wheat, rice, maize, oats, rye, barley, etc.), as well as pasture grasses,
sugar cane, and bamboo.
Poaceae pollen as the leading aeroallergen worldwide:
A review. H García-Mozo, Allergy 2017;72:1849–1858

The clinical relevance of birch pollen profilin
cross-reactivity in sensitized patients
F Wölbing, Allergy 2017;72:562–569
• 349 (80.6%) patients were
sensitized to Bet v 1,
• 44 (10.16%) patients to both
Bet v 1 and Bet v 2, and
• 15 (3.5%) patients to Bet v 2
only.
 Overlapping seasons and
cross-reactivity, especially
to grass pollen profilin,
can hamper the diagnosis
of birch pollen allergy.
 433 patients with
(+) SPT to birch pollen.
 IgE to major birch (Bet v 1)
and grass pollen (Phl p 1/p 5)
allergens and and the
profilins Bet v 2 and Phl p 12.

• From Bet v 2-sensitized
patients, 40 were also
sensitized to Phl p 12.
• SPTs demonstrated markedly
increased reactivity to grass
compared to birch pollen
extract in Bet v 2 only
sensitized patients.

• From Bet v 2-sensitized
patients, 40 were also
sensitized to Phl p 12.
• SPTs demonstrated markedly
increased reactivity to grass
compared to birch pollen
extract in Bet v 2 only
sensitized patients.
Accordingly, in most
of those patients,
clinical symptoms
precisely correlated
with grass pollen
counts.

Allergy testing in children with persistent asthma:
comparison of four diagnostic methods
A Önell, Allergy 2017;72:590–597
 71 Severe (n = 40) and
controlled (n = 31)
asthmatic children.
 Assessed for allergic
sensitization by 2
microarray systems
(Microtest and ISAC)
and by two standard
diagnostic methods
(ImmunoCAP and
skin prick test).
75%
% children with allergic asthma
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
00 –

% children sensitized to
27%
50 –
40 –
30 –
20 –
10 –
00 –
48%
18%
1-2 3-8 >5
n° allergens
 71 Severe (n = 40) and
controlled (n = 31)
asthmatic children.
 Assessed for allergic
sensitization by 2
microarray systems
(Microtest and ISAC)
and by two standard
diagnostic methods
(ImmunoCAP and
skin prick test).

Prevalence of allergy/IgE sensitization according to doctor's diagnosis,
Microtest, ISAC, ImmunoCAP, and skin prick test (SPT)

Prevalence of allergy/IgE sensitization according to doctor's diagnosis, Microtest,
ISAC ImmunoCAP, and skin prick test (SPT)
Microarray methods provided new information in 47%
of the sensitized children in comparison with results
obtained by standard diagnostic methods.

Prevalence of allergy/IgE sensitization according to doctor's diagnosis, Microtest,
ISAC ImmunoCAP, and skin prick test (SPT)
High prevalence of food and respiratory sensitization
supports the clinical guideline recommendation that allergies
should be evaluated in all children with suspected asthma.

The major findings are:
(i) a high prevalence of allergic sensitization in this asthma cohort,
(ii)a 90–92% concordance of test results between pairwise diagnostic
methods,
(iii) no significant differences in accuracy was observed for the two
microarray methods when compared to standard allergy diagnostic tests
(ImmunoCAP and SPT), and
(iv) new sIgE information was found in 47% of the sensitized patients when
using the allergen component information provided by the microarray
tests.

 New information was provided by the microarray results compared to
traditional extract-based tests.
 Detection of IgE antibodies toward Ara h 2 and Ara h 8 could be of
clinical relevance as sensitization against Ara h 2 is associated with
systemic reactions upon exposure to peanuts, whereas sensitization
to Ara h 8 is associated with oral allergy syndrome.
 Further, allergy to molds and mite is uncommon in our region (Sweeden)
and can be difficult to identify based on clinical history alone.
 The diagnosis of sensitization to these allergens can hold valuable
implications for exposure control and avoidance measures.

Component resolved Diagnosis
Cross-reactivity pollens & foods

Pru p 3, a marker allergen for lipid transfer protein
sensitization also in Central Europe
N Mothes-Luksch, Allergy 2017;72:1415–1418
• In the Mediterranean area, lipid
transfer proteins (LTPs) are
important causes of plant-food
allergies often associated with
severe allergic reactions.
• Peach LTP (Pru p 3) seems to be
the primary sensitizer.
• In Central Europe, allergen
extract-based diagnosis is
often complicated by
co-sensitization to Bet v 1,
the major birch pollen allergen,
its cross-reactive food
allergens, and profilins.

Pru p 3, a marker allergen for lipid transfer protein
sensitization also in Central Europe
N Mothes-Luksch, Allergy 2017;72:1415–1418
• We investigated the role of LTP
sensitization in Central European
patients displaying strong
allergic reactions
to plant-derived food.
Our results showed that LTP
sensitization represents a risk
factor for severe allergic
symptoms in Central Europe.

• Non-specific lipid transfer protein
(LTP) is by far the most frequent
cause of primary food allergy in adults
living in the Mediterranean area
where it also induces the largest
number of food-dependent
anaphylactic reactions.
• Based on its widespread distribution
throughout the plant kingdom and on the elevated homology between LTPs
from botanically unrelated foods, LTP-sensitized patients may experience
adverse reactions upon the ingestion of a large array of plant foods.
The clinical relevance of lipid transfer protein
R Asero, CEA 2018;48:6-12

R Asero, CEA 2018;48:6-12
• LTPs resist to both heat and pepsin digestion which makes them able
to reach the intestinal tract in an unmodified form, an essential condition
to induce systemic reactions.
• Furthermore, Pru p 3, the peach LTP, seems
to pass the gut epithelium by a fast transcellular
route which is not used by other less allergenic
LTPs (LTP1), thus inducing the production
of Th2 cytokines.
• This kind of passage underlines the importance of Pru p 3 as a sensitizer.

R Asero, CEA 2018;48:6-12
Sources of LTP reported to cause clinical allergy; IgE levels towards Pru p 3 are shown when available

Component
Resolved
Diagnosis
Per alimenti vedi
Food Allergy

Component Resolved Diagnosis
latex

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Animals (pets)

What diagnosis atopy

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