4 | DISCUSSION
In the presented study it was confirmed that the mean activity of plasma
PAF-AH activity is significantly lower in patients with a history of
anaphylaxis in the course of HVA as compared to healthy people. It
confirms the vital role of PAF in the pathogenesis of anaphylactic
reactions. Assuming that the plasma PAF-AH activity illustrates the
systemic activity of this enzyme, this fact indicates that apart from
external factors, the individual’s specific predisposition resulting
from the enzyme activity may also play an important role.
Contrary to other authors, our research did not show an obvious
correlation between PAF-AH activity and the severity of the
hypersensitivity reaction to the venom [10]. This problem has been
studied and discussed since the early 2000s. Vadas et al. analyzed the
relationship between plasma PAF-AH activity and the severity of
anaphylactic reaction after peanut consumption in children [8-9,
14]. In the prospective part of the mentioned authors study, three
groups with increasing severity of anaphylaxis were recruited. The
control was a group of non-allergic children. In contrast to our study,
it showed a trend suggesting that decreased PAF-AH activity is
associated with a more severe course of an anaphylactic reaction.
However, statistical significance was not obtained.
A statistically significant association was found in the retrospective
section of the study. It compared 9 cases of fatal peanut anaphylactic
reactions to several other groups, including children who died from
non-anaphylactic causes, non-allergic children, and children with
urticaria or peanut-induced angioedema. In all these comparisons, the
plasma PAF-AH activity was significantly lower in children who died from
anaphylaxis. The study did not show any differences in PAF-AH activity
in groups of children with bronchial asthma of varying severity [8,
9].
In subsequent years, the same researchers found that patients with the
lowest levels of plasma PAF-AH activity had a 27-fold higher risk of
severe or fatal anaphylaxis. Moreover, the plasma activity of the enzyme
was strongly correlated with the concentration of apolipoprotein B. It
is noteworthy that the activity of PAF-AH is also correlated with the
concentration of LDL and decreases during treatment with lovastatin or
fenofibrate. Therefore, it cannot be ruled out that lipid-lowering
therapy and lowering PAF-AH activity may lead to the increased risk of a
severe anaphylactic reaction in a susceptible population [14].
Finally, Vadas et al. found a correlation between PAF-AH activity and
the age of the participants, but in our study, it was lacking.
Research on the plasma PAF-AH and food anaphylaxis was also conducted in
the Moscow study groups of children with a history of food anaphylaxis,
atopic dermatitis and a negative history of allergic diseases. It was
found that children with a history of food anaphylaxis had statistically
lowered level of PAF-AH mRNA in peripheral blood compared to both other
groups of children. In the group with atopic dermatitis, the difference
was more than three times. In the group of children with a history of
food anaphylaxis, lower expression of the PAF-AH gene was associated
with a more severe course of anaphylaxis and cardiovascular symptoms
[15].
A large study on the relationship between plasma PAF-AH activity and the
severity of anaphylactic reactions to Hymenoptera venom was
carried out in a Milan (Italy). Its structure was relatively similar to
our trial. There was no statistically significant difference in PAF-AH
activity between healthy controls and patients after the mild
anaphylactic reactions of the 1st degree of severity.
The subgroups with higher severity grades had significantly and stepwise
lower mean plasma PAF-AH activity compared to the control group and to
each other. The exception has occurred for the 3rd and 4th severity
subgroups, between which the difference was statistically irrelevant.
Logistic regression showed that only PAF-AH activity was significantly
associated with the severity of anaphylaxis. The best cut-off point for
grades II-IV was 25 nmol/ml/min [10].
The outcomes of our trial differ from the results of the presented
studies. The difference in the mean activity of the enzyme between the
control group and the study subgroups was more than twofold. The highest
PAF-AH activity in a patient with a positive history of anaphylaxis was
only 17.24 nmol/min/ml. The cut-off point of 20 nmol/min/mL proposed by
Pravettoni et al. discriminates patients who are not at risk of
developing severe anaphylaxis very well, but our study suggests the
possibility of further lowering this threshold. Notwithstanding, the
most intriguing is the combination of two study subgroups - grade I-II
and III-IV. They did not differ in terms of enzyme activity (9.47 vs
10.16 nmol/min/ml, p = 0.0609 in Student’s t-test). Therefore, we did
not find a relationship between the severity of anaphylactic reaction in
the past and the plasma PAF-AH activity. This is interesting in the
context of the studies by Pravettoni et al., which show this kind of
association.
There are several potential reasons for the above-mentioned divergence.
Apart from the various size of the samples, age of the participants and
distinct local practice in qualifying patients for the different
severity grades of anaphylaxis, the discussed studies differed in
design. Unlike the first Vadas studies, it seems that our study group
comprised patients with less severe reactions, e.g. we did not
investigate cases of fatal anaphylaxis. The study performed by
Pravettoni et al. concerned only newly diagnosed patients, while our
study did not exclude patients undergoing immunotherapy. Technical
aspects affecting the results may also be important. In the Italian
study, 405 nm light was used to measure absorbance, while in our trial
wavelength was 412 nm. The dilution of samples could also be different;
however, to the extent permitted by the manufacturer of the assay kit.
Irrespective of the presented explanations, the results of our study
confirming the participation of PAF-AH in the pathogenesis of
anaphylaxis lead to the consideration of the practical application of
the measurements of plasma PAF-AH. In our population, all patients with
a history of anaphylaxis had decreased PAF-AH activity. This confirms
that the determination of PAF-AH activity can be a particularly useful
tool in the stratification of the individual risk of anaphylaxis toHymenoptera venoms, especially in beekeepers. Assuming that the
clinical effect of stinging, on the one hand, depends on the strength of
the anaphylactic effect of the venom, and on the other hand on the
individual properties of the sensitized person, the measurement of
PAF-AH plasma activity allows us to assess a significant internal factor
influencing the occurrence of symptoms. Perhaps the test could also help
in the diagnosis of non-allergic and idiopathic anaphylaxis —
distinguishing the true anaphylaxis from numerous conditions with
similar symptoms, such as somatoform disorders. Presently, the only
laboratory test widely used in such cases is the measurement of tryptase
concentration during an acute episode, which is often impossible to
perform for obvious reasons. The measurement of plasma PAF-AH activity
could provide a lot of diagnostic information, even months or years
after an anaphylaxis episode.
Unfortunately, our study plan did not take into account the group of
patients with other severe forms of hypersensitivity without a history
of an anaphylactic reaction. This would allow us to answer whether the
decreased PAF-AH activity occurs only in patients with anaphylaxis, or
in general in patients with severe hypersensitivity to one or more
factors.
A relatively wide dispersion of the results of plasma PAF-AH activity
was found in the control group. Noteworthy, this group was selected
primarily on the basis of negative atopic history. It is impossible to
predict a priori whether some of these people will be at risk of
developing anaphylaxis in the future. Perhaps currently healthy
individuals with low PAF-AH activity could be considered capable of
developing an anaphylactic reaction in the future. The distribution of
results in the control group may also suggest the presence of PAF-AH
gene polymorphisms in the Polish population, which strongly affect the
enzyme activity. These problems will be the subject of further research.