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Review
Nut Allergenicity: Effect of Food Processing
Carmen Cuadrado 1, * , África Sanchiz 1and Rosario Linacero 2
Citation: Cuadrado, C.; Sanchiz, Á.;
Linacero, R. Nut Allergenicity: Effect
of Food Processing. Allergies 2021,1,
150–162. https://doi.org/10.3390/
10.3390/allergies1030014
Academic Editor: Pierre Rougé
Received: 30 April 2021
Accepted: 26 July 2021
Published: 2 August 2021
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Copyright: © 2021 by the authors.
Licensee MDPI, Basel, Switzerland.
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Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
1Food Technology Department, SGIT-INIA, Ctra. La Coruña Km. 7.5, 28040 Madrid, Spain;
africa.sanchiz@gmail.com
2Genetics, Physiology and Microbiology, Biology Faculty, Complutense University, 28040 Madrid, Spain;
charolin@ucm.es
*Correspondence: cuadrado@inia.es; Tel.: +34-91-347-6925
Abstract:
Nuts are considered healthy foods due to their high content of nutritional compounds
with functional properties. However, the list of the most allergenic foods includes tree nuts, and
their presence must be indicated on food labels. Most nut allergens are seed storage proteins,
pathogenesis-related (PR) proteins, profilins and lipid transfer proteins (LTP). Nut allergenic proteins
are characterized by their resistance to denaturation and proteolysis. Food processing has been
proposed as the method of choice to alter the allergenicity of foods to ensure their safety and improve
their organoleptic properties. The effect of processing on allergenicity is variable by abolishing
existing epitopes or generating neoallergens. The alterations depend on the intrinsic characteristics
of the protein and the type and duration of treatment. Many studies have evaluated the molecular
changes induced by processes such as thermal, pressure or enzymatic treatments. As some processing
treatments have been shown to decrease the allergenicity of certain foods, food processing may
play an important role in developing hypoallergenic foods and using them for food tolerance
induction. This work provides an updated overview of the applications and influence of several
processing techniques (thermal, pressure and enzymatic digestion) on nut allergenicity for nuts,
namely, hazelnuts, cashews, pistachios, almonds and walnuts.
Keywords:
allergens; food hypersensitivity; nuts; thermal processing; pressure processing; enzy-
matic digestion
1. Introduction
Currently, the main cause of anaphylactic reactions in Western countries is food
allergies. It has been estimated that food allergies affect between 1 and 3% of the general
population and up to 8% of children. Food allergies cause more than 30,000 anaphylactic
reactions in the US [
1
]. In Europe, food allergies are the leading cause of anaphylaxis,
and between 10 and 18% of anaphylactic reactions occur at school [
2
]. The list containing
the 14 most allergenic foods in the European Union includes peanuts and tree nuts. In
accordance with Regulation (EU) No. 1169/2011, the presence of nuts must be indicated
on food labels [
3
]. After fruit, peanuts and tree nuts are the most prevalent cause of allergic
reactions in Spain (26%) [
4
]. However, nuts are increasingly consumed in the last years due
to their health benefits, which are attributable to their high content of protein, unsaturated
fatty acids, vitamins and antioxidants [5].
Nut allergen proteins belong to seed storage proteins, such as legumin (11–13S globu-
lin composed of acidic subunits of 30–40 kDa and basic 15–20 kDa), vicilin (7S globulin
of approximately 50–60 kDa) and 2S albumin (15 kDa) [
6
]. Nut allergenic proteins are
characterized by their resistance to denaturation and proteolysis [
7
]. Other nut allergens,
such as pathogenesis-related (PR) proteins, profilins and lipid transfer proteins (LTP), are
considered to be panallergens because they contribute to the allergenicity of a large group
of seeds, pollen, nuts, fruit and other plants [8].
Food processing is used in the industry to ensure safety and to enhance organoleptic
properties, in addition to altering food allergenicity. Food processing can modify the
Allergies 2021,1, 150–162. https://doi.org/10.3390/allergies1030014 https://www.mdpi.com/journal/allergies
Allergies 2021,1151
structure, properties and function of proteins, and as a result, the IgE-binding capacity of
allergens can be affected. As some processing treatments have been shown to decrease the
allergenicity of certain foods, food processing may play an important role in developing
hypoallergenic foods and using them for food tolerance induction. Other processes, how-
ever, can increase the allergenicity of some foods [
9
]. Heat treatment modifies the structure
of proteins, and therefore, epitopes and their immunogenic potential can be affected. This
effects depends on both technological parameters and the type of matrix [
10
,
11
]. The effect
of processing on allergenicity is variable and, as such, new allergenic compounds can be
generated, while existing reactive epitopes can also be damaged or destroyed [
12
–
15
]. The
structural changes produced using treatments such as boiling, microwave heating and
pressure-cooking, and their effects on legume and nut allergenicity, have been evaluated.
Importantly, findings indicate that heat- or pressure-based processing reduces IgE-binding
capacity [
12
–
18
]. Overall, the effects of processing methods on mitigating or aggravating
allergies are largely unknown. This review collected data published between 2010 and 2020
regarding the effects of processing, with and without heating, on allergens from several
tree nuts. This review attempts to provide an updated overview on how conventional and
novel processing methods influence the immunoreactive potency of allergenic proteins in
the most frequently consumed nuts: cashews, pistachios, hazelnuts, almonds and walnuts.
2. Most Prevalent Allergenic Nuts and Their Predominant Allergens
Nuts are a rich source of protein and other nutritional compounds with functional
properties. This promotes their presence in manufactured foods. In Europe, tree nut
allergies are common [
19
], with a hazelnut allergy being the most prevalent tree nut allergy.
In the US, peanuts and tree nuts, such as almonds, walnuts or cashews, seem to be more
common allergenic sources [20].
Table 1summarizes the main nut allergens. Several hazelnut proteins have been
described as allergens: Cor a 1 (Bet v 1 homologue), Cor a 2 (profilin), Cor a 8 (lipid
transfer protein (LPT)), Cor a 9 (11S legumin), Cor a 11 (7S vicilin), Cor a 14 (2S albumin)
and the oleosins Cor a 12, Cor a 13 and Cora a 15 [
21
]. Ana o 1 (7S vicilin) [
22
], Ana o 2
(11S legumin) [
23
] and Ana o 3 (2S albumin) have been identified and characterized as
cashew allergens [
24
]. Pistachios are also well characterized for their allergenic potential
and display high cross-reactivity with cashews and mangoes [
25
]. The five major allergens
in pistachios are one 2S albumin (Pis v 1), two 11S legumins (Pis v 2 and 5), one 7S vicilin
(Pis v 3) and one superoxide dismutase (Pis v 4) [
25
–
28
]. Most of the epitopic regions of Pis
v 1 and Pis v 3 showed a high degree of similarity with the Ana o 1, Ana o 2 and Ana o 3
epitopes. This is considered to be the molecular basis for the IgE-binding cross-reactivity
observed between pistachios and cashews [
29
]. In almonds, six allergenic proteins have
been characterized: Pru du 3 (LTP), Pru du 4 (profilin), Pru du 5 (60S ribosomal protein),
Pru du 6 (11S legumin), Pru du 8 (antimicrobial seed storage protein) and Pru du 10
(mandelonitrile lyase 2) [
30
]. Thus far, five allergenic proteins have been identified in
walnuts: Jug r 1 (2S albumin), Jug r 2 (7S vicilin), Jug r 3 (LTP), Jug r 4 (11S legumin) and
Jug r 5 (profilin) [
31
]. The major allergen in walnuts is Jug r 4, which is highly homologous
with other 11S globulin allergens, such as Cor a 9 (hazelnut), Ana o 2 (cashew) and Ara h 3
(peanut), explaining their IgE cross-reactivity [31].
Allergies 2021,1152
Table 1. Allergens in nuts (WHO/IUIS Allergen Nomenclature Subcommittee).
Source Allergen Protein Family MW* (kDa)
Hazelnut
(Corylus avellana)
Cor a 1
Cor a 2
Cor a 8
Cor a 9
Cor a 11
Cor a 12
Cor a 13
Cor a 14
Cor a 15
Pathogen-related protein (PR10)
Profilin
Non-specific lipid transfer protein
(LTP)
11S globulin/legumin
7S globulin/vicilin
Oleosin
Oleosin
2S albumin
Oleosin
17
14
9
40
47
17
14–16
16
17
Cashew
(Anacardium occidentale)
Ana o 1
Ana o 2
Ana o 3
Vicilin-like protein
Legumin-like protein
2S albumin
50
55
14
Pistachio
(Pistachia vera)
Pis v 1
Pis v 2
Pis v 3
Pis v 4
Pis v 5
2S albumin
11S globulin/legumin
7S globulin/vicilin
Manganese Superoxide dismutase
11S globulin/legumin
7
32
55
25.7
36
Almond
(Prunus dulcis)
Pru du 3
Pru du 4
Pru du 5
Pru du 6
Pru du 8
Pru du 10
Non-specific lipid transfer protein
1(LTP) Profilin
60S acidic ribosomal protein P2
11S globulin/legumin
Antimicrobial seed storage protein
Mandelonitrile lyase 2
9
14
10
60
31
60
Walnut
(Juglans regia)
Jug r 1
Jug r 2
Jug r 3
Jug r 4
Jug r 5
2S albumin
7S globulin/vicilinNon-specific lipid
transfer protein (LTP)
11S globulin/legumin
Profilin
15
44
9
36
20
Brazil nut
(Bertholletia excelsa)
Ber e 1
Ber e 2
2S sulfur-rich albumin
11S globulin
9
29
Chestnut
(Castanea sativa)
Cas s 5
Cas s 8
Cas s 9
Chitinase
Non-specific lipid transfer protein 1
Cytosolic class I small heat
shock protein
12–13
17
MW*: molecular weight.
A study reported that the prevalence of tree nut allergies in the US was greater than
1.1% and was more common in individuals under 18 years of age [
20
]. In 2005, the Euro-
pean Commission funded a large Europe-wide research project (EuroPrevall) designed to
evaluate and provide a broad overview of the prevalence, basis and cost of food allergies.
For this project, 56 partners from 19 European countries collaborated [
32
]. Studies involved
community surveys, birth cohort studies and clinical studies using double-blind placebo-
controlled food challenges (DBPCFC) and SPT. The project provided knowledge about
the prevalence of food allergies, as well as the ranking of allergenic foods (food groups)
as a function of the number of reactions they provoke both in the overall population and
in specific population groups (regarding age and geographic location). In this context,
Lyons et al. [33]
reported that the highest prevalence of nut allergies was estimated for
hazelnut (4%) in accordance with challenge tests and sensitization assessed by SPT. Nut
allergies appear to affect adults and adolescents more, probably due to their late intro-
duction into the diet [
34
]. Hazelnuts are widely consumed in Europe and presented a
high prevalence of positive reactions in a double blind, placebo-controlled food challenge
(DBPCFC) [
19
]. In the US, 7.5% of the total of 188 participants were found to be allergic to
hazelnuts in a 11-year follow-up study [
35
]. The effects of variety showed no influence on
Allergies 2021,1153
the allergenicity of hazelnuts, with Cor a 9 and Cor a 1 being the predominant IgE-binding
proteins in 13 European varieties [
36
]. Cashews are the second most allergic nut and a
significant health problem in the US [
37
]. The anaphylactic reactions to cashew are, often,
severe clinical manifestations, and even more dangerous than with peanuts. Cashew nuts
are consumed all over the world due to their beneficial effects on human health, but they
have also been reported to cause allergic reactions in sensitized patients [
38
]. In a study by
Rance et al. [
39
], it was concluded that 2-year-old infants are more at risk among children
sensitive to cashew nuts. The reactions were triggered in three-quarters of cases at first
exposure. A possible explanation for this finding is that there is a correlation between
earlier exposure to cashew nuts and a greater cashew nut allergy [
40
]. The symptoms upon
the ingestion of cashews were also reported to be more severe compared to those caused
due to exposure to other food allergens, such as nuts and peanuts [
38
]. Pistachio nuts are
widely consumed all over the world and primarily produced in Iran and the United States.
However, they have also been observed to cause significant allergic reactions in people sen-
sitive to the allergens Pis v 1, Pis v 2 and Pis v 3 [
41
]. Sicherer et al. [
35
] estimated an allergy
to pistachios in approximately 10% of the individuals evaluated. Almonds can provide
many health benefits due to their low glycemic index and being a source of vitamin E and
energy, manganese, fiber, protein and various polyphenolic components [
5
]. Almonds are
ranked third after walnuts and cashews in eliciting allergic reactions [
35
], although some
almond-allergic patients tend to pass oral food challenges, probably because many profilin-
sensitized patients do not exhibit symptoms [
30
]. Amandin, or Almond Major Protein, is
primarily responsible for IgE-mediated immunoreactivity. Walnuts are considered to be
responsible for the highest number of allergic reactions in sensitized subjects [
31
], but they
have health benefits, such as reducing the risk of diabetes and cardio-vascular diseases [
5
].
3. Food Processing
The reasons for consuming processed foods include ensuring preservation and safety;
improving quality, such as flavor, color and taste; convenience; variety; out of season
availability; and lack of equipment, time or skills needed for home food preparation of
certain foods. A significant quantity of food is processed at home by consumers, in addition
to industrial food processing and in institutional settings. The type of processing method
can be chosen by product type, scale of processing, available infrastructure, consumer
preferences and product sensory qualities. These reasons explain that the same raw food
can be often processed differently [
42
]. As the majority of foods are usually consumed
after processing, it was also relevant to understand the protein characteristics which are
influenced by processing, such as stability against heat and pressure, as well as mechanical
and chemical activities [
43
]. Thermal processing methods, such as boiling, frying, roasting,
baking, pressure cooking or microwave heating, are applied to certain food products before
consumption to improve their suitability for specific applications [
44
]. Non-thermal food
processing, such as high hydrostatic pressure (HHP) or enzymatic treatment, can be applied
to some foods. These processing treatments can modify the biochemical characteristics of
proteins or generate chemical reactions within the food matrix components.
4. Effect of Thermal Processing on Food Allergens
Thermal and non-thermal processing methods are applied to foods to improve their
preservation, quality, safety and suitability for specific product applications. The process-
ing can affect the solubility, digestibility and other related parameters. Through thermal
treatments, proteins can form oligomers, or become aggregated, denatured, fragmented or
re-assembled, and these modifications can produce a decreased solubility [
45
]. The overall
IgE-binding capacity of a particular extract can be more or less antigenic or result in new
allergens (neoallergens) as a consequence of heat processing [
46
]. Thermal processing anal-
ysis is, therefore, necessary for assessing the allergenicity of existing and newly introduced
foods [
11
]. The influence of heat processing mainly depends on the temperature and time
conditions used. In addition, interactions with other food matrix constituents can affect
Allergies 2021,1154
the structure of a protein. Generally, the loss of a secondary structure occurs when the
temperature is around 70–80
◦
C, while at 80–90
◦
C, rearrangements of disulfide bonds
and the formation of new bonds take place. Aggregation occurs at higher temperatures
(90–100 ◦C) [47].
The influence of a wide variety of treatments on the allergenicity of nuts has been
studied (Figure 1, Table 2) [
44
,
48
,
49
]. Thermal treatments in walnuts [
17
]; HHP in hazel-
nuts [
50
]; and roasting, blanching, autoclaving and microwave heating in almonds [
51
]
have been analyzed, and the results differ depending on the material and the conditions
of the treatments studied. Studies with walnuts have indicated that the digestibility of
protein probably increases after heat treatment, so the absorption of the protein can also
increase in the gastrointestinal tract, and due to this, the possibility of allergens eliciting an
allergenic response decreases [
52
]. However, in some cases, thermal processing may cause
some neoantigens that were not originally present to form or the digestibility of a particular
allergen may be reduced. These neoantigens may present an additional problem, and these
facts can enhance the allergenic manifestation in sensitized patients. The formation of
some neoantigens can be produced by the Maillard reaction when sugar residues interact
with proteins during heating, generating sugar-conjugated protein derivatives, which
enhance the allergenicity of some proteins, such as 2S albumins [
53
]. However, glycation
and aggregation from the Maillard reaction reduced the Ig E binding capacity of legumins
and did not affect the IgE-binding capacity of vicilins and nsLTP [43]
Allergies 2021, 1, FOR PEER REVIEW 6
Figure 1. Summary of food processing methods and their applications in the reviewed
nuts.
Table 2. Effects of processing on IgE immunoreactivity of nut allergens.
Source
Processing Conditions
IgE Reactivity
*
Reference
Hazelnut
Roasting 140 °C, 40 min
↓
Hansen et al. [55]
Roasting 144 °C, time not indicated
↓
Worm et al. [56]
Autoclaving 138 °C, 15 and 30 min
↓↓
Lopez et al. [57]; Cuadrado et al. [58]
HHP 300–600 MPa, 15 min
=
Prieto et al. [50]; Cuadrado et al. [58]
Cashew
Boiling, 100 °C, 30 and 60 min
= (↓)
Cuadrado et al. [14]; Sanchiz et al.
[15]
Boiling, 100 °C, 15 min + sodium sulfite
↓
Mattison et al. [59]
Frying, 191 °C, 1 min
= (↓)
Su et al. [60]
Roasting 200 °C, 15 min
↑
Venkatachalam et al. [61]
Autoclaving 138 °C, 15 and 30 min
↓
Cuadrado et al. [14]; Sanchiz et al.
[15]
Autoclaving 138 °C, 30 min + Amano 3DS 120 min
↓↓
Cuadrado et al. [14]
DIC 7 bar, 2 min
↓↓
Vicente et al. [62]
Pistachio
Boiling, 100 °C, 30 and 60 min
= (↓)
Cuadrado et al. [14]; Sanchiz et al.
[15]
Steaming
↓
Noorbakhsh et al. [63];
Autoclaving 138 °C, 15 and 30 min
↓
Cuadrado et al. [14]; Sanchiz et al.
[15]
Autoclaving 138 °C, 30 min + Amano SD 60 min
↓↓
Cuadrado et al. [14]
DIC 7 bar, 2 min
↓↓
Vicente et al. [62]
Almond
Boiling, 100 °C, 5 and 10 min
=
Su et al. [60]
Frying, 191 °C, 1 min
= (↓)
Su et al. [60]
Roasting 180 °C, 15 min
=
Su et al. [60]
Autoclaving 121 °C, 30 min
=
Venkatachalam et al. [51]
Autoclaving 138 °C, 15 and 30 min
↓↓
Cuadrado et al. [58]
HHP 300–600 MPa, 15 min
=
Cuadrado et al. [58]
Walnut
Frying, 191°C, 1 min
= (↓)
Su et al. [60]
Roasting 160 °C, 30 min; 177 °C, 12 min
=
Su et al. [60]
Autoclaving 138 °C, 15 and 30 min
↓↓
Cabanillas et al. [17].
Figure 1. Summary of food processing methods and their applications in the reviewed nuts.
The IgE recognizes and interacts with epitopes belonging to allergenic proteins.
Two types of IgE binding epitopes are possible, either linear or conformational ones.
In linear epitopes, amino acid is arranged in linear order in the polypeptide chain, while in
the conformational epitopes, amino acids are far apart in the primary sequence but may
come together during the folding of the polypeptide chain. Linear epitopes may be more
problematic as compared to the conformational ones, as they are mostly resistant to heat
treatment. Thermal processing mainly affects conformational epitopes as the bonds can
be broken down due to heat. Refolding allows the formation of native conformational
epitopes, but few new allergens may be formed, which requires further efforts to minimize
the risk associated with neoantigens [
54
]. Thus, thermal processing can strongly alter the
structure, function and allergenicity of foods.
Allergies 2021,1155
Table 2. Effects of processing on IgE immunoreactivity of nut allergens.
Source Processing Conditions IgE Reactivity * Reference
Hazelnut
Roasting 140 ◦C, 40 min ↓Hansen et al. [55]
Roasting 144 ◦C, time not indicated ↓Worm et al. [56]
Autoclaving 138 ◦C, 15 and 30 min ↓↓ Lopez et al. [57]; Cuadrado et al. [58]
HHP 300–600 MPa, 15 min = Prieto et al. [50]; Cuadrado et al. [58]
Cashew
Boiling, 100 ◦C, 30 and 60 min = (~↓) Cuadrado et al. [14]; Sanchiz et al. [15]
Boiling, 100 ◦C, 15 min + sodium sulfite ~↓Mattison et al. [59]
Frying, 191 ◦C, 1 min = (~↓) Su et al. [60]
Roasting 200 ◦C, 15 min ~↑Venkatachalam et al. [61]
Autoclaving 138 ◦C, 15 and 30 min ↓Cuadrado et al. [14]; Sanchiz et al. [15]
Autoclaving 138
◦
C, 30 min + Amano 3DS 120 min
↓↓ Cuadrado et al. [14]
DIC 7 bar, 2 min ↓↓ Vicente et al. [62]
Pistachio
Boiling, 100 ◦C, 30 and 60 min = (~↓) Cuadrado et al. [14]; Sanchiz et al. [15]
Steaming ~↓Noorbakhsh et al. [63];
Autoclaving 138 ◦C, 15 and 30 min ↓Cuadrado et al. [14]; Sanchiz et al. [15]
Autoclaving 138 ◦C, 30 min + Amano SD 60 min ↓↓ Cuadrado et al. [14]
DIC 7 bar, 2 min ↓↓ Vicente et al. [62]
Almond
Boiling, 100 ◦C, 5 and 10 min = Su et al. [60]
Frying, 191 ◦C, 1 min = (~↓) Su et al. [60]
Roasting 180 ◦C, 15 min = Su et al. [60]
Autoclaving 121 ◦C, 30 min = Venkatachalam et al. [51]
Autoclaving 138 ◦C, 15 and 30 min ↓↓ Cuadrado et al. [58]
HHP 300–600 MPa, 15 min = Cuadrado et al. [58]
Walnut
Frying, 191◦C, 1 min = (~↓) Su et al. [60]
Roasting 160 ◦C, 30 min; 177 ◦C, 12 min = Su et al. [60]
Autoclaving 138 ◦C, 15 and 30 min ↓↓ Cabanillas et al. [17].
HHP 300–600 MPa, 15 min = Cabanillas et al. [17].
* IgE reactivity determined by different techniques and conditions. Pictography: =,
↓
,
↑
, ~, are a symbolic representation of the global effect
of the specific treatment on the IgE reactivity of a given food (=, similar; ↑, increase; ↓, decrease; ~ ↑, slight increase; ~↓, slight decrease).
5. Effect of Non-Thermal Processing on Food Allergens
Non-thermal processing includes a large number of processing techniques without
heating the food to produce modifications in the product. There are a wide variety of pro-
cesses which induce a change in the conformation structure of the proteins that fall under
this category: enzymatic digestion, high hydrostatic pressure, ultrafiltration, fermentation,
gamma radiation, pulsed ultraviolet light, ultrasound, etc. (Figure 1). In gamma radiation
or pulsed ultraviolet light, the internal energy of molecules can increase when a high
dosage of radiation is applied, which can be translated into increased temperatures. The
effects of enzymatic hydrolysis on the allergenicity and digestibility of food proteins have
been widely reported. Enzymatic hydrolysis under sonication and autoclaving separately
resulted in a significant decrease in the IgE-binding capacity of cashew and pistachio nuts
(Table 2). Pistachio allergens were more affected by these treatments. However, enzymatic
digestion combined with heat was necessary to drastically reduce the IgE-binding capacity
of cashew allergens. Highly effective simultaneous processing conditions to abolish the
allergenic potency of cashew and pistachio nuts have been proposed [
14
]. It is important
that the evaluation of different enzyme activities to reduce allergenicity is carried out with
sera from patients with documented clinical allergy to the source food [64]. However, the
use of sera from patients with documented allergies is not enough to address allergenicity.
For allergenicity assessment, the serum needs to be combined with assays simulating
in vivo
allergic reactions (BAT, mediator release assays), although the most reliable assays
involve oral food challenge [43].
Moreover, stability under gastric conditions has been regarded as a useful parameter
for the identification of allergens [
65
,
66
], and
in vitro
assays for pepsin digestion were
included in a 2001 FAO/WHO protocol for the allergenicity assessment of novel food
Allergies 2021,1156
proteins [
67
]. For the development of special formulations, an alternative to intact proteins
is enzymatic protein hydrolysates designed to provide nutritional support to specific
population groups, such as infants, elderly, and food-allergic patients. In addition, protein
hydrolysates show technological advantages. Extensive enzymatic treatment combined
with food processing treatments, such as heat and ultrafiltration, is considered highly
effective to obtain protein products with an added high value for human nutrition and
decreased allergenicity [14].
High pressure alters the tertiary and quaternary structure of most globular proteins
without influence on the secondary structure. Thus, high hydrostatic pressure can unfold
proteins. The pressure needed for the unfolding range from 100 MPa to 1 GPa, being
500 MPa the most effective, although it varies from protein to protein [
68
]. The effect of
HHP on allergenicity and changes in protein structure of immunoreactive proteins has been
investigated in and in nuts such as hazelnut and almond [
58
]. Hazelnut allergens showed
changes in solubility after processing at high pressure (300–600 MPa) for 15 min, although
the immunoreactivity was not affected after HHP processing [
50
,
58
]. The same HHP
conditions of pressure and time did not produce any change on almond immunoreactive
proteins [
58
]. Most plant allergens are pressure stable since pressure processing methods
(e.g., HHP) normally contribute to maintain the protein in its native-like state when
compared with temperature processing. The IgE-binding capacity of nsLTP, profilins,
vicilins and PR-10 is not affected by the application of high pressure, while for 2S albumins
and legumins, it can be slightly reduced Combination of pressure-heat and pressure-heat
enzymatic hydrolysis treatments is more efficient in reducing the IgE-binding capacity of
nsLTP, legumins and vicilins, because pressure changes protein at conformational level
making it more susceptible to enzyme activity and temperature [43]
6. Effect of Processing on Nut Allergens
6.1. Hazelnut
Hansen et al. [
55
] evaluated the effect of processing on hazelnuts, and they observed
a reduction in allergenicity after roasting them at 140
◦
C for 40 min. However, 29% of
the subjects showed allergic symptoms upon the consumption of roasted hazelnuts and,
therefore, this reduction is not of clinical significance. Thus, for the population suffering
from sensitization towards hazelnuts, especially Cor a 1 and Cor a 2, the consumption of
roasted hazelnuts cannot be recommended as an alternate method [
55
]. Worm et al. [
56
] also
reported the impact of roasting hazelnuts at 144
◦
C on allergic patients. They found that
roasting might reduce the risk in most hazelnut-sensitized patients, although the hazelnut
allergens are considered to be heat stable and are responsible for causing severe reactions
in the sensitive population. Conventional thermal treatments between temperatures of
100 and 185
◦
were also evaluated, indicating that hazelnut allergens, especially allergens
of lower molecular weight (14 kDa), offer high resistance against thermal treatments [
69
]
(Table 2). Lopez et al. [
57
] and Cuadrado et al. [
58
] analyzed the influence of autoclaving
and high-pressure processing on hazelnut immunoreactivity. In this study, they concluded
that autoclaving, especially at a temperature of 138
◦
C for 15–30 min decreased the allergens
Cor a 1, Cora 8, Cor a 9 and Cor a 11. However, hazelnut allergens showed no reduction in
immunoreactivity after processing at high pressure (300–600 MPa), although the protein
solubility was affected after HHP processing [
50
]. The glycation reaction between the
amino acid groups of protein with reducing sugars occurring in Maillard reactions was
reported to be responsible for reducing the immunoreactivity of Cor a 11 allergen, but Cor
a 1 and Cor a 9 were unaffected even after glycation in the presence of glucose at 70
◦
C [
70
].
6.2. Cashew
The characterization of IgE and IgG immunoreactive proteins from untreated and
thermal-treated cashew samples was comparatively studied (Table 2) [
14
,
15
,
58
]. The results
indicated that boiling for 60 min did not affect to the IgG-binding proteins from cashews.
However, cashews subjected to autoclaving (heat under pressure) showed a reduction
Allergies 2021,1157
in IgG-reactive bands. A band probably corresponding to the Ana o 3 (13 kDa) [
10
] was
especially immunoreactive. In the samples treated with heat and pressure, the IgE reactive
bands were drastically reduced. This result cannot be explained by a potential loss in the
solubility of proteins due to thermal treatments, since the experiments were carried out
under strong protein solubilization conditions [
58
]. A combination of heat and pressure
treatments (autoclaving) was able to decrease the IgE-binding properties of cashews. After
autoclaving at 138
◦
C for 30 min, the IgG immunodetection of Ana o 2 and Ana o 3
was strongly diminished. The influence of other thermal pressured treatments, such as
instant controlled pressure drop (DIC), on cashew allergenic capacity was evaluated [
62
].
The extreme conditions of DIC (7 bar, 120 s) strongly reduced the immunodetection of
allergenic proteins when IgE sera from sensitized patients were used for Western blots.
The number of IgE-immunoreactive proteins was reduced by 67.2% [
62
]. Such reduction in
immunodetection had a greater effect on pistachios (75%) than cashew nuts, but was not
totally eliminated. Therefore, cashew proteins are probably more resistant than pistachio
proteins. The observed degradation of proteins after extreme heat/pressure treatments
obtained was similar to the degradation produced by some enzymatic treatments in our
previous findings [
14
]. Enzymatic digestion for 2 h under sonication with Protease P 3DS
(Amano) reduced the number of IgE-binding protein bands recognized by the sera of
cashew-allergic patients. The recognition of Ana o 2 was almost eliminated, but some
digestion-resistant proteins were detected by 50% of the tested sera and Ana o 3 was still
recognized by IgE in one patient [
14
]. A more effective method to reduce the allergenic
reactivity of cashews was the combination of both enzymatic hydrolysis under sonication
and thermal treatment.
Although cashew proteins showed high resistance to all processing methods used,
autoclaving or a combination of
γ
-irradiation and autoclaving is able to cause a reduction
in allergen detection [
60
,
61
]. Mattison et al. [
59
] found that sodium sulfite and heating
treatment can alter the structure of specific cashew allergens, decreasing their IgE-binding
potency. The stability of cashew allergens to
in vitro
digestion has been studied and
identified, and Ana o 3 IgE-binding epitopes are the most resistant [
71
]. The same authors
also evaluated the solubility of cashew proteins by SDS-PAGE and LC-MS/MS. They
found that it was modified by heat treatment, and the relative amount of peptides from
specific cashew allergens was also affected as well as the IgE-binding capacity of the
extracts [
72
]. Oleic acid has been found to reduce the IgE-binding capacity of cashew
allergens [
73
,
74
].
In vitro
studies are important preliminary tests to ensure a possible
reduction in IgE cross-linking capacity, before performing further clinical studies.
In vivo
clinical relevant experiments—such as SPT and mediator release assays (MRA), in which the
IgE cross-linking capacity of processed food proteins is analyzed in effector cells of allergy—
constitute an essential part on the research of allergenic properties of processed food since
an altered ability of food allergens to bind IgE using traditional
in vitro
immunoassays is
not always directly related to a modified allergenic function [15].
6.3. Pistachio
The effects of dry roasting and steaming on the allergenicity of pistachio protein were
studied (Table 2). The authors reported that the steaming reduced the reactivity of the
pistachio allergens compared to dry roasting methods. Pistachios were soaked for 12 h
prior to any processing in a solution containing lemon water (pH 3.2–3.2) and sodium
chloride (1.6% w/v). They concluded that the ionic strength of the soaking solution in
combination with steaming might modify the secondary structure of the protein, resulting
in reduced reactivity. They found no significant difference in various sensory attributes,
including aroma, color, flavor, taste and overall acceptability [63].
Recently, it has been demonstrated that there is an important reduction in 11S and 2S
protein detection by autoclave treatment at 138
◦
C for 30 min. In contrast, LTP was even
detected after autoclaving under the same conditions. The IgE binding of pistachio proteins
decreased by 73% after boiling, and the lowest detection was found under the hardest
Allergies 2021,1158
autoclave conditions [
58
]. Similarly to cashews, the IgE immunoreactivity of pistachios
was strongly decreased after heat treatment under high pressure (autoclaving at 256 kPa),
but not with autoclaving at 120 kPa or boiling, which has been confirmed by SPT and
MRA experiments [
15
], indicating that pistachio autoclaved at 256 kPa for 30 min showed
an strong reduction in allergenic potency. These results are also in concordance with our
previous findings for other tree nuts and legumes [
12
,
13
,
15
–
17
]. Similarly to cashews
and peanuts, the influence of an instant controlled pressure drop (DIC) on pistachio IgE-
binding capacity was evaluated, and the data indicated that the IgE immunodetection
of allergenic pistachio proteins was markedly reduced under the harshest conditions of
DIC (7 bar, 120 s) [
62
]. Such reduction in immunodetection is more effective in pistachios
(75%) than in cashew nuts (67.2%), but is not completely eliminated. According to these
findings, instant controlled pressure drop (DIC) can be considered to be an adequate
technique for obtaining hypoallergenic pistachio flour for use in the food industry. The
effect of enzymatic hydrolysis on pistachio allergens was more effective than that on cashew
allergens according to our previous results [
14
]. Most IgE-binding proteins from untreated
and processed pistachio samples were hydrolyzed with Protin (E5) after 1 h of sonication.
Such assays included the enzymatic digestion of total protein from whole nut paste (as
opposed to soluble extract) under sonication (ultrasound disruption). The whole nut paste
was prepared by mixing pistachio defatted flour with distilled water (0.5 g/mL). In this
case, the IgE immunoreactivity of pistachios was almost eliminated after the enzymatic
digestion of raw and thermally treated samples. The results of protein identification by MS
analysis showed that, after the enzymatic treatment, the allergens were degraded due to the
thermal treatment and enzymatic digestion. The enzymatic digestion of thermally treated
samples produced few resistant peptides, indicating that some fragments of allergenic
pistachio and cashew proteins survive even after heat and enzymatic treatments. According
to Cuadrado et al. [
14
], enzymatic hydrolysis has a greater effect on autoclaved cashew
and pistachio samples compared to untreated cashew and pistachio samples.
6.4. Almond
Roux et al. [
75
] investigated the stability of amandin in different almond cultivars, and
the results showed a reduction of approximately 40% in reactivity in different blanched
and dry roasted cultivars in comparison to unprocessed almonds, but this reduction is not
clinically relevant [
75
]. Venkatachalam et al. [
51
] also reported the effects of autoclaving,
roasting, blanching and microwave processing on amandin. Autoclaving and microwave
processing methods were ineffective, which showed that amandin was heat stable towards
thermal processing methods, which are normally employed in food industries [
76
]. Only
pulsed UV light treatment produced changes in the surface properties of the protein, which
can reduce the viable binding sites for IgE when entering the human body, probably due
to protein fragmentation as a result of the photo-thermal effect [
77
]. Cuadrado et al. [
58
]
demonstrated that after autoclaving at 138
◦
C for 30 min, the IgG immunoreactivity of
Pru du 6, Pru du 2S and Pru du 3 is strongly diminished. They showed that thermal and
pressure treatment combined in autoclaving was able to reduce the IgE-binding properties
of almonds, but HHP up to 600 MPa did not affect almond immunoreactivity, in agreement
with Costa et al. [
43
], who reported that most plant allergens are pressure stable. (Table 2).
6.5. Walnut
Different studies have found that walnut allergenic proteins are highly resistant to
processing and do not show any reduction in IgE reactivity (Table 2) [
78
]. Downs [
52
]
also evaluated the effects of roasting on walnut protein, and the data indicated that the di-
gestibility of 11S legumin and 7S vicilin increased after processing, which can be attributed
to secondary structure modifications in the protein and, in some cases, to lower immunore-
activity. Barre et al. [
79
] concluded that the secondary structure of Jug r 1 allergen is stable
under thermal treatment up to 90
◦
C. Cabanillas et al. [
17
] evaluated the effect of heat
treatments in combination with high-pressure processing on walnuts. It was demonstrated
Allergies 2021,1159
that pressure treatment at 256 kPa and 138
◦
C effectively reduced the IgE-binding capacity
of walnut proteins, whereas pressure treatments (up to 600 MPa) without heating did not
affect walnut immunoreactivity, although pressure-treated walnut proteins showed higher
susceptibility to digestion.
7. Conclusions
In recent years, an increase in food allergies around the world, especially sensitivity to
tree nuts, has been reported. This review provides an updated overview of the effect of
processing with and without heating on the immunoreactive potency of allergenic proteins
of the most widely consumed nuts. Although some processing methods have achieved
promising results in reducing the IgE reactivity of nuts, the relevance of these results at the
clinical level is still unclear.
It is highly important to understand how processing affects the structural properties
of allergenic proteins and its relationship with changes in allergenicity (aggravating or
mitigating). The most common feature promoting plant protein allergenicity is molecular
stability, related to structural resistance to heat and proteolysis. Therefore, it is critical
to analyze how the degree of processing can modify digestibility, solubility and other
parameters related to IgE reactivity depending on the type of protein. Legumins and
cereal prolamins are less reactive when undergoing protein aggregation, while the same
phenomenon leads to an increase in 2S albumin reduction. Certain processing methods
can alter some allergenic proteins, resulting in the destruction of the epitopes, but they are
unaltered in others. In this way, processing can modify the overall IgE binding profiles
of nut proteins. However, as
in vitro
assays are only an indicator of
in vivo
allergenic-
ity, further
in vitro
analysis and
in vivo
clinical data are required to confirm that these
treatments can effectively reduce the
in vivo
allergenicity of these nuts. These putative
hypoallergenic foods could be safely consumed and even utilized as desensitizing food
only after such studies.
Author Contributions:
Conceptualization, C.C.; methodology, Á.S. and C.C.; investigation, Á.S.,
R.L. and C.C.; formal analysis, Á.S. and C.C.; resources, C.C.; data curation, Á.S., R.L. and C.C;
writing—original draft preparation, C.C.; writing—review and editing, R.L. and C.C.; supervision,
C.C.; project administration, C.C.; funding acquisition, C.C. All authors have read and agreed to the
published version of the manuscript.
Funding:
This research was funded by the Spanish Ministerio de Ciencia e Innovación, grant number
AGL2017-83082-R.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
Jerschow, E.; Lin, R.Y.; Scaperotti, M.M.; McGinn, A.P. Fatal anaphylaxis in the United States, 1999–2010: Temporal patterns and
demographic associations. J. Allergy Clin. Immunol. 2014,134, 1318–1328.e7. [CrossRef] [PubMed]
2.
Muraro, A.; Agache, I.; Clark, A.; Sheikh, A.; Roberts, G.; Akdis, C.A.; Borrego, L.M.; Higgs, J.; Hourihane, J.O.; Jorgensen, P.;
et al. EAACI food allergy and anaphylaxis guidelines: Managing patients with food allergy in the community. Allergy
2014
,69,
1046–1057. [CrossRef] [PubMed]
3.
Regulation (EU) 1169/2011EC of the European Parliament and of the Council of 25 October 2011on the Provision of Food Information to
Consumers, Amending Regulations (EC) No 1924/2006 and (EC) No 1925/2006 of the European Parliament and of the Council; Official
Journal of the European Union: Bruxelles, Belgium, 2011; pp. 18–43.
4. Fernandez Rivas, M. Food allergy in Alergologica-2005. J. Investig. Allergol. Clin. Immunol. 2009,2, 37–44.
5. Ros, E. Health benefits of nut consumption. Nutrients 2010,2, 652–682. [CrossRef]
6.
Crespo, J.F.; James, J.M.; Fernandez-Rodriguez, C.; Rodriguez, J. Food allergy: Nuts and tree nuts. Br. J. Nutr.
2006
,96, S95–S102.
[CrossRef]
7. Roux, K.H.; Teuber, S.S.; Sathe, S.K. Tree nut allergens. Int. Arch. Allergy Immunol. 2003,131, 234–244. [CrossRef]
8. Radauer, C.; Breiteneder, H. Evolutionary biology of plant food allergens. J. Allergy Clin. Immunol. 2007,120, 518. [CrossRef]
9.
Cabanillas, B.; Novak, N. Effects of daily food processing on allergenicity. Crit. Rev. Food Sci. Nutr.
2019
,59, 31–42. [CrossRef]
[PubMed]
10.
Mills, C.; Johnson, P.E.; Zuidmeer-Jongejan, L.; Critenden, R.; Wal, J.M.; Asero, R. Effect of Processing on the Allergenicity of
Foods. In Risk Management for Food Allergy; Elsevier: Amsterdam, The Netherlands, 2013; pp. 227–251.
Allergies 2021,1160
11. Wal, J.M. Thermal processing and allergenicity of foods. Allergy 2003,58, 727–729. [CrossRef]
12.
Álvarez-Álvarez, J.; Guillamón, E.; Crespo, J.F.; Cuadrado, C.; Burbano, C.; Rodríguez, J.; Fernández, C.; Muzquiz, M. Effects
of extrusion, boiling, autoclaving, and microwave heating on lupine allergenicity. J. Agric. Food Chem.
2005
,53, 1294–1298.
[CrossRef]
13.
Cuadrado, C.; Cabanillas, B.; Pedrosa, M.M.; Varela, A.; Guillamon, E.; Muzquiz, M.; Crespo, J.F.; Rodriguez, J.; Burbano, C.
Influence of thermal processing on IgE reactivity to lentil and chickpea proteins. Mol. Nutr. Food Res.
2009
,53, 1462–1468.
[CrossRef]
14.
Cuadrado, C.; Cheng, H.; Sanchiz, A.; Ballesteros, I.; Easson, M.; Grimm, C.C.; Dieguez, M.C.; Linacero, R.; Burbano, C.;
Maleki, S.J. Influence of enzymatic hydrolysis on the allergenic reactivity of processed cashew and pistachio. Food Chem.
2018
,
241, 372–379. [CrossRef] [PubMed]
15.
Sanchiz, A.; Cuadrado, C.; Dieguez, M.C.; Ballesteros, I.; Rodriguez, J.; Crespo, J.F.; Cuevas, N.L.; Rueda, J.; Linacero, R.;
Cabanillas, B.; et al. Thermal processing effects on the IgE-reactivity of cashew and pistachio. Food Chem.
2018
,245, 595–602.
[CrossRef]
16.
Cabanillas, B.; Maleki, S.J.; Rodriguez, J.; Burbano, C.; Muzquiz, M.; Aranzazu Jimenez, M.; Pedrosa, M.M.; Cuadrado, C.;
Crespo, J.F. Heat and pressure treatments effects on peanut allergenicity. Food Chem. 2012,132, 360–366. [CrossRef] [PubMed]
17.
Cabanillas, B.; Maleki, S.J.; Rodriguez, J.; Cheng, H.; Teuber, S.S.; Wallowitz, M.L.; Muzquiz, M.; Pedrosa, M.M.; Linacero, R.;
Burbano, C.; et al. Allergenic properties and differential response of walnut subjected to processing treatments. Food Chem.
2014
,
157, 141–147. [CrossRef]
18.
Cabanillas, B.; Pedrosa, M.M.; Rodriguez, J.; Muzquiz, M.; Maleki, S.J.; Cuadrado, C.; Burbano, C.; Crespo, J.F. Influence of
Enzymatic Hydrolysis on the Allergenicity of Roasted Peanut Protein Extract. Int. Arch. Allergy Immunol.
2012
,157, 41–50.
[CrossRef]
19.
Ortolani, C.; Ballmer-Weber, B.K.; Hansen, K.S.; Ispano, M.; Wüthrich, B.; Bindslev-Jensen, C. Hazelnut allergy: A double- blind,
placebo-controlled food challenge multicenter study. J. Allergy Clin. Immunol. 2000,105, 577–581. [CrossRef] [PubMed]
20.
Weinberger, T.; Sicherer, S. Current perspectives on tree nut allergy: A review. J. Asthma Allergy
2018
,11, 41–51. [CrossRef]
[PubMed]
21.
Costa, J.; Mafra, I.; Carrapatoso, I.; Oliveira, M.B.P.P. Hazelnut Allergens: Molecular Characterization, Detection, and Clinical
Relevance. Crit. Rev. Food Sci. Nutr. 2016,56, 2579–2605. [CrossRef]
22.
Wang, F.; Robotham, J.M.; Teuber, S.S.; Tawde, P.; Sathe, S.K.; Roux, K.H. Ana o 1, a cashew (Anacardium occidentale L.) allergen of
the vicilin seed storage protein family. J. Allergy Clin. Immunol. 2002,110, 160–166. [CrossRef]
23.
Wang, F.; Robotham, J.M.; Teuber, S.S.; Sathe, S.K.; Roux, K.H. Ana o 2, a major cashew (Anacardium occidentale L.) nut allergen of
the legumin family. Int. Arch. Allergy Immunol. 2003,132, 27–39. [CrossRef]
24.
Robotham, J.M.; Wang, F.; Seamon, V.; Teuber, S.S.; Sathe, S.K.; Sampson, H.A.; Beyer, K.; Seavy, M.; Roux, K.H. Ana o 3, an
important cashew nut (Anacardium occidentale L.) allergenof the 2S albumin family. J. Allergy Clin. Immunol.
2005
,115, 1284–1290.
[CrossRef] [PubMed]
25.
Noorbakhsh, R.; Mortazavi, S.A.; Sankian, M.; Shahidi, F.; Tehrani, M.; Azad, F.J.; Behmanesh, F.; Varasteh, A. Pistachio
allergy-prevalence and in vitro cross-reactivity with other nuts. Allergol. Int. 2011,60, 425–432. [CrossRef] [PubMed]
26.
Ahn, K.; Bardina, L.; Grishina, G.; Beyer, K.; Sampson, H.A. Identification of two pistachio allergens, Pis v 1 and Pis v 2, belonging
to the 2S albumin and 11S globulin family. Clin. Exp. Allergy 2009,39, 926–934. [CrossRef] [PubMed]
27.
Ayuso, R.; Grishina, G.; Ahn, K. Identification of a MnSOD-like protein as a new major pistachio allergen. J. Allergy Clin. Immunol.
2007,119, s115. [CrossRef]
28.
Willison, L.N.; Tawde, P.; Robotham, J.M.; Penney, R.M.; Teuber, S.S.; Sathe, S.K.; Roux, K.H. Pistachio vicilin, Pis v 3, is
immunoglobulin E-reactive and cross-reacts with the homologous cashew allergen, Ana o 1. Clin. Exp. Allergy
2008
,38, 1229–1238.
[CrossRef]
29.
Barre, A.; Nguyen, C.; Granier, C.; Benoist, H.; Rougé, P. IgE-Binding Epitopes of Pis v 1, Pis v 2 and Pis v 3, the Pistachio
(Pistacia vera) Seed Allergens. Allergies 2021,1, 63–91. [CrossRef]
30.
Costa, J.; Mafra, I.; Carrapatoso, I.; Oliveira, M.B. Almond allergens: Molecular characterization, detection, and clinical relevance.
J. Agric. Food Chem. 2012,60, 1337–1349. [CrossRef] [PubMed]
31.
Costa, J.; Carrapatoso, I.; Oliveira, M.B.; Mafra, I. Walnut allergens: Molecular characterization, detection and clinical relevance.
Clin. Exp. Allergy 2014,44, 319–341. [CrossRef] [PubMed]
32.
Mills, C.; Mackie, A.; Burney, P.; Beyer, K.; Frewer, L.; Madsen, C.; Botjes, E.; Crevel, R.; van Ree, R. The prevalence, cost and basis
of food allergy across Europe. Allergy 2007,62, 717–722. [CrossRef]
33.
Lyons, S.; Clausen, M.; Knulst, A.; Ballmer-Weber, B.; Fernandez-Rivas, M.; Barreales, L.; Bieli, C.; Dubakiene, R.; Pérez, C.;
J˛edrzejczak-Czechowicz, M.; et al. Prevalence of Food Sensitization and Food Allergy in Children Across Europe. J. Allergy Clin.
Immunol. Pract. 2020,8, 2736–2746. [CrossRef]
34.
Zuidmeer, L.; Goldhahn, K.; Rona, R.J.; Gislason, D.; Madsen, C.; Summers, C.; Sodergren, E.; Dahlstrom, J.; Lindner, T.;
Sigurdardottir, S.T.; et al. The prevalence of plant food allergies: A systematic review. J. Allergy Clin. Immunol.
2008
,121,
1210–1218.e4. [CrossRef]
35.
Sicherer, S.H.; Munoz-Furlong, A.; Godbold, J.H.; Sampson, H.A. US prevalence of self-reported peanut, tree nut, and sesame
allergy: 11-year follow-up. J. Allergy Clin. Immunol. 2012,125, 1322–1326. [CrossRef]
Allergies 2021,1161
36.
Ribeiro, M.; Costa, J.; Mafra, I.; Cabo, S.; Silva, A.P.; Gonçalves, B.; Hillion, M.; Hébraud, M.; Igrejas, G. Natural Variation of
Hazelnut Allergenicity: Is There Any Potential for Selecting Hypoallergenic Varieties? Nutrients 2020,12, 2100. [CrossRef]
37.
Clark, A.T.; Anagnostou, K.; Ewan, P.W. Cashew nut causes more severe reactions than peanut: Case matched comparison in
141 children. Allergy 2007,62, 913–916. [CrossRef] [PubMed]
38.
Mendes, C.; Costa, J.; Vicente, A.A.; Oliveira, M.B.; Mafra, I. Cashew Nut Allergy: Clinical Relevance and Allergen Characterisa-
tion. Clin. Rev. Allergy Immunol. 2019,57, 1–22. [CrossRef] [PubMed]
39.
Rance, F.; Bidat, E.; Bourrier, T.; Sabouraud, D. Cashew allergy: Observations of 42 children without associated peanut allergy.
Allergy 2003,58, 1311–1314. [CrossRef] [PubMed]
40.
van der Valk, J.P.; Dubois, A.E.; Gerth van Wijk, R.; Wichers, H.J.; de Jong, N.W. Systematic review on cashew nut allergy. Allergy
2014,69, 692–698. [CrossRef]
41.
Costa, J.; Silva, I.; Vicente, A.A.; Oliveira, M.B.P.P.; Mafra, I. Pistachio nut allergy: An updated overview. Crit. Rev. Food Sci. Nutr.
2019,59, 546–562. [CrossRef]
42.
Cuadrado, C.; Pedrosa, M. Legume Allergenicity: The effect of food processing In Legumes for Global Food Security; Jimenez-Lopez, J.C.,
Clemente, A., Eds.; Nova Science Publishers, Inc.: New York, NY, USA, 2017; pp. 223–248.
43. Costa, J.; Bavaro, S.; Benedé, S.; Diaz-Perales, A.; Bueno-Diaz, C.; Gelencser, E.; Klüber, J.; Larre, C.; Lozano-Ojalvo, D.; Lupi, R.;
et al. Are Physicochemical Properties Shaping the Allergenic Potency of Plant Allergens? Clin. Rev. Allergy Immunol.
2020
, 1–36.
[CrossRef]
44.
Masthoff, L.J.; Hoff, R.; Verhoeckx, K.C.; van Os-Medendorp, H.; Michelsen-Huisman, A.; Baumert, J.L.; Pasmans, S.G.; Meijer, Y.;
Knulst, A.C. A systematic review of the effect of thermal processing on the allergenicity of tree nuts. Allergy
2013
,68, 983–993.
[CrossRef]
45. Maleki, S.J. Food processing: Effects on allergenicity. Curr. Opin. Allergy Clin. Immunol. 2004,4, 241–245. [CrossRef]
46.
Schmitt, D.A.; Nesbit, J.B.; Hurlburt, B.K.; Cheng, H.; Maleki, S.J. Processing can alter the properties of peanut extract preparations.
J. Agric. Food Chem. 2010,58, 1138–1143. [CrossRef]
47. Davis, P.; Williams, S. Protein modification by thermal processing. Allergy 1998,53, 102–105. [CrossRef]
48.
Jiménez-Saiz, R.; Benedé, S.; Molina, E.; López-Expósito, I. Effect of Processing Technologies on the Allergenicity of Food Products.
Crit. Rev. Food Sci. Nutr. 2015,55, 1902–1917. [CrossRef]
49.
Vanga, S.K.; Raghavan, V. Processing Effects On Tree Nut Allergens: A Review. Crit. Rev. Food Sci. Nutr.
2016
,57, 2077–2094.
[CrossRef] [PubMed]
50.
Prieto, N.; Burbano, C.; Iniesto, E.; Rodriguez, J.; Cabanillas, B.; Crespo, J.; Pedrosa, M.; Muzquiz, M.; del Pozo, J.; Linacero, R.;
et al. A Novel Proteomic Analysis of the Modifications Induced by High Hydrostatic Pressure on Hazelnut Water-Soluble
Proteins. Foods 2014,3, 279–289. [CrossRef]
51.
Venkatachalam, M.; Teuber, S.S.; Roux, K.H.; Sathe, S.K. Effects of roasting, blanching, autoclaving, and microwave heating on
antigenicity of almond (Prunus dulcis L.) proteins. J. Agric. Food Chem. 2002,50, 3544–3548. [CrossRef]
52.
Downs, M.L.; Simpson, A.; Custovic, A.; Semic-Jusufagic, A.; Bartra, J.; Fernandez-Rivas, M.; Taylor, S.L.; Baumert, J.L.;
Mills, E.N.C. Insoluble and soluble roasted walnut proteins retain antibody reactivity. Food Chem.
2016
,194, 1013–1021. [CrossRef]
[PubMed]
53.
Maleki, S.J.; Chung, S.Y.; Champagne, E.T.; Raufman, J.P. The effects of roasting on the allergenic properties of peanut proteins. J.
Allergy Clin. Immunol. 2000,106, 763–768. [CrossRef]
54.
Sathe, S.K.; Sharma, G.M. Effects of food processing on food allergens. Mol. Nutr. Food Res.
2009
,53, 970–978. [CrossRef]
[PubMed]
55.
Hansen, K.S.; Ballmer-Weber, B.K.; Leuttkopf, D.; Skov, P.S.; Weuthrich, B.; Bindslev-Jensen, C.; Vieths, S.; Poulsen, L.K. Roasted
hazelnuts—Allergenic activity evaluated by double-blind, placebo-controlled food challenge. Allergy Eur. J. Allergy Clin. Immunol.
2003,58, 132–138. [CrossRef] [PubMed]
56.
Worm, M.; Hompes, S.; Fiedler, E.M.; Illner, A.K.; Zuberbier, T.; Vieths, S. Impact of native, heat-processed and encapsulated
hazelnuts on the allergic response in hazelnut-allergic patients. Clin. Exp. Allergy 2009,39, 159–166. [CrossRef]
57.
Lopez, E.; Cuadrado, C.; Burbano, C.; Jimenez, M.A.; Rodriguez, J.; Crespo, J.F. Effects of autoclaving and high pressure on
allergenicity of hazelnut proteins. J. Clin. Bioinform. 2012,2, 1–13. [CrossRef]
58.
Cuadrado, C.; Sanchiz, A.; Vicente, F.; Ballesteros, I.; Linacero, R. Changes Induced by Pressure Processing on Immunoreactive
Proteins of Tree Nuts. Molecules 2020,25, 954. [CrossRef]
59.
Mattison, C.P.; Desormeaux, W.A.; Wasserman, R.L.; Yoshioka-Tarver, M.; Condon, B.; Grimm, C.C. Decreased immunoglobulin
E (IgE) binding to cashew allergens following sodium sulfite treatment and heating. J. Agric. Food Chem.
2014
,62, 6746–6755.
[CrossRef]
60.
Su, M.; Venkatachalam, M.; Teuber, S.S.; Roux, K.H.; Sathe, S.K. Impact of
γ
-irradiation and thermal processing on the antigenicity
of almond, cashew nut and walnut proteins. J. Sci. Food Agric. 2004,84, 1119–1125. [CrossRef]
61.
Venkatachalam, M.; Monaghan, E.K.; Kshirsagar, H.H.; Robotham, J.M.; O’Donnell, S.E.; Gerber, M.S.; Roux, K.H.; Sathe, S.K.
Effects of processing on immunoreactivity of cashew nut (Anacardium occidentale L.) seed flour proteins. J. Agric. Food Chem.
2008
,
56, 8998–9005. [CrossRef]
62.
Vicente, F.; Sanchiz, A.; Rodriguez-Perez, R.; Pedrosa, M.; Quirce, S.; Haddad, J.; Besombes, C.; Linacero, R.; Allaf, K.; Cuadrado, C.
Influence of Instant Controlled Pressure Drop (DIC) on Allergenic Potential of Tree Nuts. Molecules 2020,25, 1742. [CrossRef]
Allergies 2021,1162
63.
Noorbakhsh, R.; Mortazavi, S.A.; Sankian, M.; Shahidi, F.; Maleki, S.J.; Nasiraii, L.R.; Falak, R.; Sima, H.R.; Varasteh, A. Influence
of processing on the allergenic properties of pistachio nut assessed
in vitro
.J. Agric. Food Chem.
2010
,58, 10231–10235. [CrossRef]
64. Lucas, J.S.; Atkinson, R.G. What is a food allergen? Clin.Exp. Allergy 2008,38, 1095–1099. [CrossRef]
65.
Moreno, F.J. Gastrointestinal digestion of food allergens: Effect on their allergenicity. Biomed. Pharmacother.
2007
,61, 50–60.
[CrossRef]
66.
Pali-Schöll, I.; Untersmayr, E.; Klems, M.; Jensen-Jarolim, E. The Effect of Digestion and Digestibility on Allergenicity of Food.
Nutrients 2018,10, 1129. [CrossRef]
67.
FAO. Evaluation of Allergenicity of Genetically Modified Foods. In Report of a Joint FAO/WHO Expert Consultation on Allergenicity
of Foods Derived from Biotechnology; FAO: Rome, Italy, 2001.
68. Somkuti, J.; Smeller, L. High pressure effects on allergen food proteins. Biophys. Chem. 2013,4622, 19–29. [CrossRef]
69.
Wigotzki, M.; Steinhart, H.; Paschke, A. Influence of varieties, storage and heat treatment on IgE-binding proteins in hazelnuts
(Corylus avellana). Food Agric. Immunol. 2000,12, 217–229. [CrossRef]
70.
Cucu, T.; Platteau, C.; Taverniers, I.; Devreese, B.; de Loose, M.; de Meulenaer, B. ELISA detection of hazelnut proteins: Effect of
protein glycation in the presence or absence of wheat proteins. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess
2011,28, 1–10. [CrossRef] [PubMed]
71.
Mattison, C.P.; Grimm, C.C.; Wasserman, R.L.
In vitro
digestion of soluble cashew proteins and characterization of surviving
IgE-reactive peptides. Mol. Nutr. Food Res. 2014,58, 884–893. [CrossRef]
72.
Mattison, C.P.; Bren-Mattison, Y.; Vant-Hull, B.; Vargas, A.M.; Wasserman, R.L.; Grimm, C.C. Heat-induced alterations in cashew
allergen solubility and IgE binding. Toxicol. Rep. 2016,3, 244–251. [CrossRef]
73.
Chung, S.Y.; Mattison, C.P.; Reed, S.; Wasserman, R.L.; Desormeaux, W.A. Treatment with oleic acid reduces IgE binding to
peanut and cashew allergens. Food Chem. 2015,180, 295–300. [CrossRef]
74.
Shi, X.; Guo, R.; White, B.L.; Yancey, A.; Sanders, T.H.; Davis, J.P.; Burks, A.W.; Kulis, M. Allergenic properties of enzymatically
hydrolyzed peanut flour extracts. Int. Arch. Allergy Immunol. 2013,162, 123–130. [CrossRef] [PubMed]
75.
Roux, K.H.; Teuber, S.S.; Robotham, J.M.; Sathe, S.K. Detection and stability of the major almond allergen in foods. J. Agric. Food
Chem. 2001,49, 2131–2136. [CrossRef]
76.
Su, M.; Liu, C.; Roux, K.H.; Gradziel, T.M.; Sathe, S.K. Effects of processing and storage on almond (Prunus dulcis L.) amandin
immunoreactivity. Food Res. Int. 2017,100, 87–95. [CrossRef] [PubMed]
77.
Li, Y.; Yang, W.; Chung, S.-Y.; Chen, H.; Ye, M.; Teixeira, A.; Gregory, J.; Welt, B.; Shriver, S. Effect of Pulsed Ultraviolet Light and
High Hydrostatic Pressure on the Antigenicity of Almond Protein Extracts. Food Bioprocess Technol. 2011,6, 431–440. [CrossRef]
78.
Doi, H.; Touhata, Y.; Shibata, H.; Sakai, S.; Urisu, A.; Akiyama, H.; Teshima, R. Reliable enzyme-linked immunosorbent assay for
the determination of walnut proteins in processed foods. J. Agric. Food Chem. 2008,56, 7625–7630. [CrossRef]
79.
Barre, A.; Sordet, C.; Culerrier, R.; Rance, F.; Didier, A.; Rouge, P. Vicilin allergens of peanut and tree nuts (walnut, hazelnut and
cashew nut) share structurally related IgE-binding epitopes. Mol. Immunol. 2008,45, 1231–1240. [CrossRef] [PubMed]
