Structure
and function of LTPs
Plant LTPs are small molecules 91-95
amino acid residues, with a molecular mass around 9kDa
and high isoelectric point. These homologuous proteins
belong to the so-called α-class proteins, which share
common three-dimensional structure, with four α-helices
kept together by four disulfide bridges between eight
cysteine residues at conserved positions. This structure
of LTPs has a functional role, as it provides a hydrophobic
cavity which can accommodate a fatty acyl chain, allowing
the binding of phospholipids and their transferring across
membranes. It is probably responsible for the extreme
resistance of LTPs to physical and chemical treatments(proteolysis,
heat, chemical and oxidative processes).
LTPs play a role in the formation of the cellular membrane,
by conveying phospholipids(particularly waxes and cutin)
to the membrane. LTPs have been found to be expressed
in epidermal or peripheral cell layers of cutinized organs,
it was hypothesized that they might be involved in the
deposition of cutin monomers or other lipophillic substances.
The preferred location of LTPs in outer cell layers may
also be a clue to their role in repulsion or suppression
of pathogenic attack from outside. This function is confirmed
by the fact that LTPs are induced in stressed conditions(wounding,
drought stress, low temperature and osmotic stress) and
by fungal/bacterial infection.
Route
of sensitization
Allergic reactions to plant-derived foods
in patients with OAS are usually due to sensitization
to pollens which contain allergens cross-reacting with
homologous molecules in foods. The primary sensitization
takes place towards the inhalant allergens(pollen of birch,
mugwart etc), and food allergy develops only secondarily
as a result of a molecular cross-reactivity. The homologues,
however, are labile allergens, as they are rapidly destroyed
by pepsin digestion, heat and oxidative process.
More recently, studies from Mediterranean area, reported
allergic reactions to plant-derived foods in nonpollen-allergic
patients. In these patients, the most frequently involved
allergens were LTPs, which behave as “true” food allergens,
capable of sensitizing through the gastrointestinal tract.
Sensitization to LTPs was not related to a previous sensitization
to birch pollen. No cross reactivity was demonstrated
between pollen allergens and LTPs.
Although sensitization to LTPs is commonly believed to
take place primarily by the oral route, the peculiar geographical
distribution of LTP sensitization(frequent in Mediterranean
area), led to the hypothesis of an environmental factor
that favors LTP sensitization.
Clinical
relevance of LTP sensitization
LTPs have been found to be relevant allergens
in many plant-related foods. Cross-reactivity among LTPs
from different plant foods has been widely documented.
This extensive cross-reactivity is probably due to the
ubiquitous distribution of LTPs throughout the plant kingdom
which makes sensitization to multiple foods very common
in LTP-allergic patients, give rise to the so-called “LTP
syndrome”. It is interesting to notice that IgE cross-reactivity
between different LTPs is found when the amino acid sequence
identity is quite high.
Allergy to foods of plant origin is usually caused by
cross-reactivity between pollen and vegetables or fruits:
a typical model is the birch-fruit syndrome. This syndrome
is characterized by symptomatic primary sensitization
to birch pollen, with respiratory symptoms beginning months
or years before the food-related symptoms, which are usually
mild and limited to the oral mucosa(the so-called “oral
allergy syndrome”).
Reactivity to LTP in plant-derived foods gives rise to
a completely different clinical picture: LTPs contained
in foods pass intact through the gastrointestinal tract
and are able to come into contact with the immune system
and to elicit an IgE-mediated response. Another characteristic
of LTP allergy is the high frequency of severe systemic
reactions(such as anaphylaxis, urticaria, angioedema,
asthma, glottis oedema etc).
New tools
for diagnosis
The most recent studies use purified
or recombinant allergens for the in vitro or in vivo diagnosis
of food allergy: it is felt that this approach is far
more sensitive and specific than the use of the whole
food extracts, because the single pure allergens can be
standardized in concentration and biological activity,
and are much more stable than the antigens present in
the food extract, because they are not in contact with
other components of the plant matrix responsible for degradation.
Conclusions
LTPs show a highly conserved three-dimensional
structure, which is responsible for their resistance to
gastric pH and peptic digestion and for their stability
upon heating and processing of foods, making them ideal
food allergens. LTPs from different allergenic sources
show extensive IgE cross-reactivity, which is at the basis
of multiple sensitizations to foods. LTP-sensitized subjects
show a higher prevalence of systemic symptoms up to severe
anaphylaxis. Finally, LTP allergy has a peculiar geographical
distribution with predominance in the Mediterranean area,
but the reason for this is still unknown: the role of
genetic factors was not studied, while the importance
of dietary habits suggested. LTP allergy is a typical
and unique kind of food allergy in which further studies
are needed. |
