Changes in CD4⁺CD25⁺FoxP3⁺ Regulatory T Cells and Serum Cytokines in Sublingual and Subcutaneous Immunotherapy in Allergic Rhinitis with or without Asthma

Abstract

<b><i>Background:</i></b> Few studies have directly compared the immunologic responses to specific subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). <b><i>Objective:</i></b> We aimed to directly compare clinical efficacy and immunological responses between SLIT and SCIT in allergic rhinitis (AR) sensitized to house dust mites. <b><i>Methods:</i></b> Sixty-seven patients (age 5–55 years) with moderate-severe <i>Dermatophagoides pteronyssinus</i> (Der-p) and <i>Dermatophagoides farinae</i> AR with or without asthma were randomized (2:2:1) into SLIT (<i>n</i> = 27), SCIT (<i>n</i> = 26) and placebo (<i>n</i> = 14) groups. Symptom and medication scores, visual analogue score, serum Der-p specific immunoglobulin G4 (Der-p-sIgG4), CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> regulatory T cells (Tregs) and serum cytokines were measured. <b><i>Results:</i></b> After 1-year treatment, a significant improvement of total rhinitis score (TRS), total rhinitis medication score (TRMS) and visual analogue score occurred in both SLIT and SCIT. There were no differences in clinical efficacy except for TRMS (<i>p</i> = 0.026) when SLIT and SCIT were directly compared. CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> Tregs had a trend towards upregulation in the 2 modes and inversely correlated with TRS (<i>p</i> = 0.024) only in SLIT. Der-p-sIgG4 significantly increased in SLIT and SCIT (<i>p</i> < 0.05), and it was 30 times higher in SCIT than SLIT after the treatment (<i>p</i> < 0.05). Serum interferon-γ significantly increased only in SCIT after 1 (<i>p</i> = 0.008), 6 (<i>p</i> = 0.007) and 12 (<i>p</i> = 0.008) months of treatment and inversely correlated with TRS (<i>p</i> = 0.032). <b><i>Conclusion:</i></b> While SCIT and SLIT have similar rates of clinical improvement, the 2 modes reveal heterogeneous changes of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Tregs, sIgG4 and cytokines.

Immune maturation and modulation in childhood allergies : Aspects of epigenetic, mucosal and systemic immune mediators in allergy development and prevention

“…270,285 Furthermore, in dust mite-allergic subjects both SCIT and SLIT treatment induced higher presence of CD4+CD25+FoxP3+ Tregs compared to both controls groups and base line levels. 288 However, there was a correlation with clinical improvement only for SLIT.…”

Emerging Cell-Based Therapies in Chronic Lung Diseases: What About Asthma?

“…SLIT and SCIT upregulated CD4 + CD25 + FoxP3+ Tregs. However, only SLIT showed clinical improvement related to Tregs ( Xian et al, 2020 ). Despite these results, SCIT is just recommended as an adjunct to pharmacotherapy in individuals with asthma, and SLIT is not recommended ( Cloutier et al, 2020 ).…”

Differential DNA methylation in allergen-specific immunotherapy of asthma

“… 6 The CD4 + CD25 + Foxp3 + Treg cells induced by tolerogenic dendritic cells (DCs) in the oral mucosa mediate immune tolerance, thus improving the clinical efficacy after SLIT. 7 SLIT has no risk of severe systemic reactions, which is considered an advantage over SCIT, because allergens are mostly captured by tolerogenic DCs before they reach the mast cells during SLIT. 6 It has been suggested that SCIT contributes to the phenotypic deviation of Th2 cell responses to a protective Th1 profile, which enables SCIT to manifest earlier IFN-γ secretion than SLIT.…”

“… 6 It has been suggested that SCIT contributes to the phenotypic deviation of Th2 cell responses to a protective Th1 profile, which enables SCIT to manifest earlier IFN-γ secretion than SLIT. 7 A recent study indicated that Dermatophagoides pteronyssinus (Der p)-specific IgG4 levels in asthma treated with SCIT were almost 30 times higher than those in asthma treated with SLIT. 7 …”

“… 7 A recent study indicated that Dermatophagoides pteronyssinus (Der p)-specific IgG4 levels in asthma treated with SCIT were almost 30 times higher than those in asthma treated with SLIT. 7 …”