Frew.qxp 11/8/09 3:01 pm Page 46
Allergic Rhinoconjunctivitis
Figure 1: Allergen Immunotherapy
Allergen immunotherapy
Mast cell degranulation
lgE
?
IL-4, -13
Th2 B cell
+
Th2
Eosinophil
+
IL-5
Allergic mucosal
inflammation
Tho
and symptoms
IL-12, IFN-γ
Th1
lgG, blocking Abs
T cell ‘anergy’
+
IL-10
TGF-β
Tr cells
Th2
B cell
Ab = antibody; IFN = interferon; Ig = immunoglobulin; IL = interleukin; TGF = transforming growth factor; Th = T helper.
injected proteins and which are critical to the delivery of clinical conventional drug therapy.
6
In terms of symptom control, the mean
benefits. Following subcutaneous injection, the allergenic material level of efficacy in double-blind placebo-controlled studies is a
is taken up by phagocytic cells, with about 1% of the injected reduction in symptom and medication scores of 30–40% over and
dose reaching the regional lymph nodes. Allergen-specific above what can be achieved with drug therapy alone. In the trials,
immunoglobulin G (IgG) antibodies are produced and these hay fever patients who were multiply sensitised responded at least
increase progressively over the course of treatment. It was as well to grass pollen desensitisation as those who were
originally suggested that these antibodies might ‘block’ the allergic monosensitised to grass pollen.
response in some way. However, while the magnitude of the
IgG response reflects the amount of allergen given, it is not related Relatively limited data are available from clinical trials regarding the
directly to the degree of clinical efficacy. SIT does not abolish long-term efficacy of SIT for allergic rhinoconjunctivitis, but it has
immediate skin reactions to allergen, but successful SIT is been shown conclusively that the effects last for at least three
accompanied by a reduction in the skin and nasal late-phase years after discontinuing therapy.
7
Longer-term placebo-controlled
response to allergen, with reduced T-cell and eosinophil studies have not been performed and would be extremely difficult
recruitment after local allergen challenge.
2,3
to conduct, but open studies and anecdotal clinical evidence
suggest that most patients will have a sustained benefit of grass
SIT also alters the function of allergen-specific T cells (see Figure 1). pollen SIT for at least 10–15 years.
This can be seen both in proliferation assays and at sites
challenged with allergen.
3–5
Expression of T-helper 2 (Th2) cytokines Effects of Specific Allergen Immunotherapy
is not affected, but an increased proportion of the T cells recruited on the Natural History of Allergic Disease
after allergen express the Th1 cytokines interleukin 2 (IL-2), A proportion of patients with allergic rhinoconjunctivitis go on to
interferon-gamma and IL-12. In addition, there is induction of develop asthma each year. The annual rate of progression has been
allergen-specific CD4
+
T-regulatory cells, which express CD25, the estimated at 5%,
8
but this is not universally accepted. It has been
transcription factor fox p3 and IL-10. IL-10 has several relevant suggested that SIT may prevent or modify the development of
properties, including promotion of IgG4 production, inhibition of asthma in children with allergic rhinoconjunctivitis who have not
IgE-dependent mast cell activation, inhibition of eosinophil survival yet developed asthma. In a key study of 205 children six to 14 years
and cytokine production and suppression of T cells. These effects of age who did not have asthma diagnosed previously, SIT for birch
on allergen-specific T cells may explain why the clinical and late- or grass pollen allergy was given in an open, randomised design.
phase responses are attenuated without much impact on allergen- Three years after completing treatment, 45% of the untreated group
specific IgE antibodies. had developed asthma while only 26% of the treated group had
asthma. These results have been sustained up to seven years after
Specific Allergen Immunotherapy for completing therapy. Therefore, five children had to be treated to
Allergic Rhinoconjunctivitis prevent one case of asthma.
9
The effectiveness of SIT in seasonal allergic rhinoconjunctivitis has
been confirmed in many trials using grass, ragweed and birch SIT can also prevent the development of new allergic sensitisations.
10
pollen. In particular, SIT is effective clinically even in patients who In both open and double-blind studies, monosensitised children
have severe seasonal rhinoconjunctivitis that is resistant to treated with SIT were much less likely to acquire new sensitivities, as
46 EUROPEAN RESPIRATORY DISEASE
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68