Is there a causative
role for tetanus toxoid vaccination in the development of allergy-like
symptoms and in the increasing prevalence of atopic
diseases?
Mari A.
Allergy Unit, National
Health Service, Rome, Italy. a.mari@panservice.it
Allergic
diseases are a worldwide health problem. They mainly affect people
living in developed countries where an increasing prevalence of allergy
symptoms has been recorded in the last 20-30 years. The cause of this
increase is still disputed, and, among others, the "hygiene hypothesis"
supported the concept that relevant changes in lifestyle could have a
relationship with the phenomenon. More recently the recorded parallel
increase in autoimmune diseases has suggested to consider the "hygiene
hypothesis" as a cause of a more general disregulation of the immune
system leading to both allergy and to autoimmunity. Here are reported a
series of observations, evidence, and data from the literature leading
to a different hypothesis. The key points are: (1) the presence of two
subsets of patients having allergy symptoms based on an IgE-mediated
mechanism or not; (2) the positive results obtained with the autologous
serum skin test in either cutaneous or respiratory affected subjects,
mainly in children and adult females; (3) the presence of IgG
autoantibodies against the alpha-chain of the high affinity IgE receptor
(FcepsilonRIalpha) in non-IgE-mediated urticaria and even in respiratory
subjects; (4) the cross-reactivity between epitopes of the tetanus
toxoid molecule and the FcepsilonRIalpha detected by means of an
alpha-chain affinity purified IgG fraction; (5) the positive skin
reactivity obtained using IgG anti-tetanus toxoid preparations in
allergic and non-allergic volunteers. The presence of IgG autoantibodies
actively generated by the population-based vaccination with tetanus
toxoid could induce both mediator release from activated mast cell and
Th2 cytokine production early in life. There are epidemiological
evidences that tetanus toxoid vaccination could be linked with an
increased tendency to have allergy symptoms. The different
epidemiological distribution of non-IgE-mediated symptoms, mainly
affecting young infants would be in agreement with the present
hypothesis. The prevalent mother-to-child relationship in terms of risk
for allergy symptoms could be explained with the trans-placenta transfer
of IgG. A similar transfer could also take place through the mother milk
during breast feeding. It may thus be hypothesized that the increased
prevalence of allergic diseases could be caused by the generalized
tetanus toxoid immunization procedure, progressively extended to most of
the countries worldwide in the last 30-40 years. Both the induction of
non-IgE-mediated symptoms caused by the mast cell activation via the
anti-FcepsilonRIalpha IgG and the long lasting Th2 inflammation of
affected tissues would be the inducing mechanisms. This hypothesis would
re-configure part of the allergic diseases as a Th2 phenotypic
expression of an autoimmune disease.