A preseason booster prolongs the increase of allergen specific IgG4 levels, after basic allergen intralymphatic immunotherapy, against grass pollen seasonal allergy

Abstract

Background: Allergen specific IgG4 levels have been monitored as a surrogate marker for the tolerance inducing effect of subcutaneous immunotherapy (SCIT) in many studies. Its accuracy at group level has been well established, but IgG4 has not yet found its place in the daily care of immunotherapy patients. Methods: Intralymphatic immunotherapy (ILIT) is a novel route for allergy vaccination against pollen allergy, where an ultrasound-guided injection of 1000 SQ-U Alutard is given directly into a groin lymph node. The suggested standard dosing so far has been one injection with 4 weeks in-between. In total 3000 SQ-U with the treatment completed in 2 months. IgG4 was measured with Immulite technique and rhinoconjunctivitis symptoms were estimated with daily online questionnaires. Mann-Whitney U-test and Wilcoxon Signed Rank test were applied for comparisons between groups and within groups, respectively. Results: The present study demonstrates that a single, preseason ILIT booster of 1000 SQ-U Alutard 5-grasses ® , re-increases the allergen specific timothy-IgG4 levels, in patients already treated with ILIT before the previous pollen season. It also shows the feasibility of the ILIT-route for allergy vaccination of rhinitis patients, with or without concomitant asthma, with low degree of side effects and reconfirms high and sustained patient satisfaction. Conclusions: It is tempting to suggest that the allergen specific IgG4 levels can be used to build an intuitive algorithm for future clinical guidance of ILIT patients.

Intralymphatic immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta-analysis

“…Full-text screening for eligibility excluded 13 studies. Thirteen studies (11 RCTs and 2 cohorts) were included in the qualitative synthesis (8,9,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) of which 10 RCTs were included in the quantitative synthesis (8,(19)(20)(21)(22)(24)(25)(26)(27)(28) . A flowchart of the study selection is illustrated in Figure 1.…”

“…Inguinal lymph nodes were the site of allergen administration in 12 studies (8,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) . One study used cervical lymph nodes (9) .…”

“…One study used cervical lymph nodes (9) . Pollen extracts were administered in 10 studies that assessed seasonal ARC patients (8,(20)(21)(22)(24)(25)(26)(27)(28)(29) . In the 3 studies of patients with perennial ARC, mixed allergen extracts (house dust mites, dog, and cat dander) (23) , house dust mite allergen extracts (9) , and a recombinant MAT-Feld1 from cat dander (19) were used in each study.…”

“…The interval between the ILIT injections was 4 weeks in 12 studies (8,9,19,(21)(22)(23)(24)(25)(26)(27)(28)(29) , and 2 weeks in 1 study (20) . Escalating doses were administered in 2 studies (19,22) and fluctuating doses in 1 study (due to adverse events) (23) .…”

“…Subgroup analyses by ARC subtype, age of the participant, and injection interval were conducted to assess the treatment effects and to explore the heterogeneity. Witten (20) , 2013 (22) , 2016 Hellkvist (24) , 2018 (25) , 2020 (27) , 2020 (28) , 2020 Weinfeld (29) , 2020 were given in 3 studies (25,26,29) . Five studies had follow-up periods longer than 52 weeks (8,(25)(26)(27)29) .…”