Intra-cervical lymphatic immunotherapy for dust mite-induced allergic rhinoconjunctivitis in children: a 3-year prospective randomized controlled trial

Abstract

BackgroundPediatric allergic rhinoconjunctivitis has become a public concern with an increasing incidence year by year. Conventional subcutaneous immunotherapy (SCIT) has long treatment time, high cost and poor compliance. The novel immunotherapy significantly shortens the course of treatment by directly injecting allergens into cervical lymph nodes, which can perform faster clinical benefits to children.ObjectiveBy comparing with SCIT, this study aimed to evaluate the long-term efficacy and safety of intra-cervical lymphatic immunotherapy (ICLIT).MethodsThis is a prospective randomized controlled study. A total of 50 allergic rhinoconjunctivitis children with dust mite allergy was randomly divided into ICLIT group and SCIT group, receiving three cervical intralymphatic injections of dust mite allergen or three years of subcutaneous injection, separately. Primary outcomes included total nasal symptom scores (TNSS), total ocular symptom scores (TOSS), total symptom scores (TSS), total medication scores (TMS), and total quality of life score. Secondary outcomes included pain perception and adverse reactions during treatment. Other secondary outcome was change in Dermatophagoides pteronyssinus (Derp) and Dermatophagoides farina (Derf) -specific IgE level.ResultsBoth groups had significantly decreased TNSS, TOSS, TSS, TMS, and total quality of life score after 36 months of treatment (p<0.0001). Compared with SCIT, ICLIT could rapidly improve allergic symptoms (p<0.0001). The short-term efficacy was consistent between the two groups (p=0.07), while the long-term efficacy was better in SCIT group (p<0.0001). The pain perception in ICLIT group was lower than that in SCIT group (p<0.0001). ICLIT group was safer. Specifically, the children had only 3 mild local adverse reactions without systemic adverse reactions. The SCIT group had 14 systemic adverse reactions. At last, the serum Derp and Derf-specific IgE levels in ICLIT and SCIT groups decreased 3 years later (p<0.0001).ConclusionICLIT could ameliorate significantly the allergic symptoms in pediatric patients with an advantage in effectiveness and safety, besides an improved life quality including shortened period of treatment, frequency of drug use and pain perception.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR1800017130.

Single‐cell RNA sequencing reveals the landscape of biomarker in allergic rhinitis patient undergoing intracervical lymphatic immunotherapy and related pan‐cancer analysis

“…Successful AIT elicits allergen‐specific B cell responses with the help of T cells or alone, producing antibody isotypes derived from B cells, such as IgA, IgG, and IgE, consequently sustaining an allergen‐specific immune tolerance 19 . The ICLIT has been demonstrated as a novel, effective treatment through the evaluation of clinical outcomes and total quality of life score with an advantage in efficacy, safety, and patient adherence 15 . Even though the underlying molecular mechanism of AIT has not been fully illustrated, the perspective from immunologists insisted that the induction of immunological tolerance to allergens regulated by allergen‐specific IgE and protective IgG4 as well as IgA play a crucial role in the procedure of AIT 7,11,20 .…”

“…19 The ICLIT has been demonstrated as a novel, effective treatment through the evaluation of clinical outcomes and total quality of life score with an advantage in efficacy, safety, and patient adherence. 15 Even though the underlying molecular mechanism of AIT has not been fully illustrated, the perspective from immunologists insisted that the induction of immunological tolerance to allergens regulated by allergen-specific IgE and protective IgG4 as well as IgA play a crucial role in the procedure of AIT. 7,11,20 We herein investigated the primary B cell populations in peripheral blood from an AR patient who underwent ICLIT, using scRNA-seq to unveil the AIT-related phenotype with the transcriptome.…”

“…Intralymphatic AIT, as an alternative treatment in comparison to subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), has an advantage in treatment adherence and safety upon a satisfactory efficacy 14 . We creatively conducted intracervical lymphatic immunotherapy under ultrasound guidance and achieved an approving efficacy and safety in 3‐year random control trials 15 . Understanding the dynamic path from cell differentiation and immunoglobulin production during the AIT in a time‐dependent manner will be fundamental and help us to optimize the punctual time and dose in the injection of AIT.…”

“…14 We creatively conducted intracervical lymphatic immunotherapy under ultrasound guidance and achieved an approving efficacy and safety in 3-year random control trials. 15 Understanding the dynamic path from cell differentiation and immunoglobulin production during the AIT in a time-dependent manner will be fundamental and help us to optimize the punctual time and dose in the injection of AIT. However, the underlying mechanism and interactions between these immune regulons and cells will still be further elucidated.…”

Allergen immunotherapy in China

“…This trial demonstrated that ILIT significantly improved both symptoms and quality of life, reduced administration of rescue medication, and no moderate or severe adverse events. Another prospective randomized controlled trial, spanning over 3 years, assessed the long-term efficacy and safety of cervical ILIT in 50 children with HDM-induced allergic rhino-conjunctivitis ( 164 ). The trial showed that compared with SCIT, cervical ILIT could improve allergic symptoms more rapidly, shorten the period of treatment, and lower pain perception.…”