Intralymphatic immunotherapy of pollen-induced rhinoconjunctivitis: a double-blind placebo-controlled trial

Terese Hylander, Olivia Larsson, Ulla Petersson-Westin, Mia Eriksson, Susanna Kumlien Georén, Ola Winqvist, Lars-Olaf Cardell, Terese Hylander, Olivia Larsson, Ulla Petersson-Westin, Mia Eriksson, Susanna Kumlien Georén, Ola Winqvist, Lars-Olaf Cardell

Abstract

Background: Allergen-specific immunotherapy represents the only disease-modifying treatment for allergic diseases. We and others have previously demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, this has recently been disputed. The aim of this study was therefore to expand our previous trial, further assessing the safety and efficacy of ILIT.

Methods: Thirty-six patients with pollen-induced rhinoconjunctivitis were randomised to receive three intralymphatic inguinal injections of active allergen (1000 SQ-U birch- or grass-pollen) or placebo. Clinical effects, safety and circulating immunological markers were assessed before, 4 weeks after treatment and at the end of the consecutive pollen season.

Results: No moderate or severe reactions were recorded following ILIT. Patients receiving active ILIT experienced a significant improvement in self-recorded seasonal allergic symptoms, as compared to placebo (p = 0.05). In a subgroup of these patients ("improved"), a reduction in nasal symptoms following nasal allergen provocation was also demonstrated. No changes in total IgE or IgG4 were found. However, the affinity of allergen specific IgG4 following active treatment was significantly increased, as compared to non-improved patients (p = 0.04). This could be correlated with clinical improvement, on an individual level.

Conclusions: This double-blinded placebo-controlled study confirms that ILIT is a safe and effective treatment for pollen-induced rhinoconjunctivitis, markedly reducing seasonal allergic symptoms.

Trial registration: EudraCT: 2009-016815-39.

Figures

Fig. 1
Fig. 1
Flow diagram of study cohort. ILIT: Intralymphatic immunotherapy
Fig. 2
Fig. 2
Patient-recorded treatment outcome following three intralymphatic injections with active ILIT or placebo. Patients compared seasonal allergic symptoms after treatment, with symptoms prior to treatment. A VAS-score of 0 indicates no improvement, whereas a score of 10 indicates complete recovery. The black box signifies “improved” patients with a VAS-score above 5; the grey box signifies “non-improved” patients with a VAS-score below 1. Circles represent patients with an allergy towards birch pollen; triangles represent patients with an allergy towards grass pollen. *p < 0.05 using an Unpaired t test. ILIT: Intralymphatic immunotherapy
Fig. 3
Fig. 3
Levels of circulating immunoglobulins. IgE (a-b) and IgG4 (c-d) were measured before treatment, four weeks after treatment and after the consecutive pollen season in patients treated with active ILIT (a, c) or placebo (b, d). Analysis was performed using a repeated measures ANOVA. ILIT: Intralymphatic immunotherapy
Fig. 4
Fig. 4
Identification and nasal symptom scores of improved and non-improved patients. a Identification of patients reporting change in allergic symptoms 30 min after nasal allergen provocation (NPT), as well as change of seasonal allergic symptoms (VAS-score 0 = no improvement; VAS-score: 10 = complete recovery) after treatment. “Improved” patients are depicted with a black box. Non-improved patients are depicted with a grey box. b Self-reported allergic symptoms 30 min after nasal allergen provocation before treatment, four weeks after treatment and following the consecutive pollen season in improved, non-improved and placebo patients *p < 0.05 using a repeated measures ANOVA followed by a Dunnet’s multiple comparison post-test. ILIT: Intralymphatic immunotherapy
Fig. 5
Fig. 5
Change in IgG4 levels and affinity in improved and non-improved patients. a Levels of circulating IgG4 in improved and non-improved actively treated patients, as well as placebo patients, before treatment, four weeks after treatment and following the consecutive pollen season. Analysis was performed using a repeated measures ANOVA. b IgG4 affinity in improved and non-improved patients, measured and presented as percent allergen-bound IgG4 with increasing concentrations of ammonium thiocyanate (NH4SCN). n = 3–7 *p < 0.05 using two-way ANOVA followed by Fisher’s LSD

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