Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
Servicio de Alergia, Hospital Universitario de La Princesa (IP), Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
J Allergy Clin Immunol. 2014 Jan;133(1):130-8.e1-2. doi: 10.1016/j.jaci.2013.09.043. Epub 2013 Nov 28.
Sublingual administration of Phleum pratense allergen immunotherapy (SLIT) tablets is a clinically efficient treatment for grass pollen-induced rhinoconjunctivitis. This immunotherapy downregulates TH2 immune responses, induces tolerogenic pathways, and increases regulatory T cells. However, associated immune response markers of allergen desensitization remain undefined.
We sought to characterize the kinetics of individual changes in the immunologic response to grass tablet SLIT.
We evaluated the systemic effects of SLIT in a longitudinal analysis of humoral and cellular immune parameters in peripheral blood samples.
Grass tablet SLIT administration induced a 2-phase systemic humoral and cellular response. The TH2 response was initially exacerbated and detected as increased allergen-specific IgE (sIgE) and IgG4 (sIgG4) levels and an increase in IL-4-producing cells, followed by downregulation of the TH2 response with a shift toward a TH1 cytokine profile. T cells with a regulatory phenotype were also elicited. Statistical correlations between immunologic measurements for each patient throughout therapy indicated that TH2 response downregulation and reduction of the immediate SLIT-induced IgE response were associated with increased allergen-specific IgG4 synthesis early in therapy. TH2 response downregulation by month 4 correlated with increased frequency of CD4(+) T cells with a regulatory phenotype by 12 months.
Changes in sIgE levels after therapy were linked to a specific IgG4 response, and production of blocking antibodies correlated with TH2 response downregulation. Reduced IL-4(+) cell frequency was linked to an increase in the frequency of CD4(+) T cells with a regulatory phenotype. Changes in sIgE levels and reduced IL-4 and blocking antibody levels could thus be used as indicators of a patient's immune response to therapy.
舌下给予葎草过敏原免疫疗法（SLIT）片剂是治疗花粉引起的鼻结膜炎的有效方法。这种免疫疗法可下调 TH2 免疫应答，诱导耐受途径，并增加调节性 T 细胞。然而，与过敏原脱敏相关的免疫反应标志物仍不明确。
我们旨在描述对草片剂 SLIT 的免疫反应的个体变化的动力学。
我们通过对 SLIT 后外周血样本中的体液和细胞免疫参数进行纵向分析，评估了 SLIT 的全身作用。
草片剂 SLIT 给药诱导了 2 期全身体液和细胞反应。TH2 反应最初加剧，并表现为过敏原特异性 IgE（sIgE）和 IgG4（sIgG4）水平增加以及产生 IL-4 的细胞增加，随后 TH2 反应下调，向 TH1 细胞因子谱转变。还诱导了具有调节表型的 T 细胞。整个治疗过程中每位患者的免疫测量值之间的统计学相关性表明，TH2 反应下调和即时 SLIT 诱导的 IgE 反应减少与治疗早期过敏原特异性 IgG4 合成增加有关。到第 4 个月时 TH2 反应下调与第 12 个月时调节性 CD4(+)T 细胞频率增加相关。
治疗后 sIgE 水平的变化与特定的 IgG4 反应有关，产生的阻断抗体与 TH2 反应下调相关。IL-4(+)细胞频率的降低与调节性 CD4(+)T 细胞频率的增加相关。因此，sIgE 水平的变化和 IL-4 及阻断抗体水平的降低可用作患者对治疗免疫反应的指标。
