Antúnez Cristina, Mayorga Cristobalina, Corzo José Luis, Jurado Antonio, Torres María José
Research Unit for Allergic Diseases, Allergy Service, Carlos Haya Hospital, Málaga, Spain.
Pediatr Allergy Immunol. 2008 May;19(3):210-8. doi: 10.1111/j.1399-3038.2007.00604.x.
Although the efficacy of allergen-specific sublingual immunotherapy (SLIT) is now accepted, the underlying mechanisms remain elusive. Such mechanisms are better documented in the case of subcutaneous immunotherapy (SCIT). In order to understand the T-lymphocyte response in patients receiving SLIT, we compared children with respiratory disease monosensitized to Dermatophagoides pteronyssinus receiving SLIT or SCIT over a 2-yr period. Peripheral blood was obtained before beginning immunotherapy, and after 3 months, 1 yr and 2 yr. Total IgE, specific IgE and IgG4 to D. pteronyssinus were determined in serum. T-cell markers (CD3, CD4, CD8, CD25) and intracellular cytokine production (TNF-alpha, IL-2, IL-4 and IFN-gamma) were determined in peripheral blood mononuclear cells (PBMC) by flow cytometry. No differences between SCIT and SLIT were detected in the clinical variables or in the subjective evaluation. Although an increase in specific IgE and IgG4 was only detected in SCIT, a significant decrease in the specific IgE/IgG4 ratio was found in both groups. SCIT and SLIT experienced an increase in the CD4/CD8 ratio over time, but an increase in the CD4(+)CD25(+) and a decrease in the CD8(+)CD25(+) subsets were only found with SCIT. A slight shift from a Th2 to a Th1 pattern, measured by the IFN-gamma/IL-4 ratio, was only detected in the CD4 T cells with SCIT. A decrease in both groups was found in TNF-alpha and IL-2 production over time. Children with respiratory allergic diseases receiving SCIT or SLIT had a different immunologic response in peripheral blood during treatment, though the clinical improvement was similar. Whether SLIT induces a mucosal protective response should be studied.
尽管变应原特异性舌下免疫疗法(SLIT)的疗效现已得到认可,但其潜在机制仍不清楚。皮下免疫疗法(SCIT)的相关机制已有更充分的文献记载。为了解接受SLIT患者的T淋巴细胞反应,我们比较了在2年期间接受SLIT或SCIT治疗的、对尘螨单致敏的呼吸道疾病儿童。在免疫治疗开始前、3个月后、1年和2年后采集外周血。测定血清中针对尘螨的总IgE、特异性IgE和IgG4。通过流式细胞术测定外周血单个核细胞(PBMC)中的T细胞标志物(CD3、CD4、CD8、CD25)和细胞内细胞因子产生情况(TNF-α、IL-2、IL-4和IFN-γ)。在临床变量或主观评估中未检测到SCIT和SLIT之间的差异。虽然仅在SCIT中检测到特异性IgE和IgG4增加,但两组中特异性IgE/IgG4比值均显著降低。随着时间的推移,SCIT和SLIT的CD4/CD8比值均升高,但仅在SCIT中发现CD4(+)CD25(+)亚群增加和CD8(+)CD25(+)亚群减少。通过IFN-γ/IL-4比值衡量,仅在接受SCIT的CD4 T细胞中检测到从Th2模式向Th1模式的轻微转变。随着时间的推移,两组的TNF-α和IL-2产生均减少。接受SCIT或SLIT治疗的呼吸道过敏性疾病儿童在治疗期间外周血中的免疫反应不同,尽管临床改善相似。SLIT是否诱导黏膜保护反应有待研究。