Sousa Letícia, Martín-Sierra Carmen, Pereira Celso, Loureiro Graça, Tavares Beatriz, Pedreiro Susana, Martinho António, Paiva Artur
1Stemlab, S.A, Biocant Park, Núcleo 4, Lote 2, Cantanhede, Portugal.
2Flow Cytometry Unit, Clinical Pathology Service, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, Ed. S. Jerónimo, 3° piso, 30001-301 Coimbra, Portugal.
Allergy Asthma Clin Immunol. 2018 Nov 15;14:45. doi: 10.1186/s13223-018-0271-8. eCollection 2018.
Specific subcutaneous immunotherapy (SCIT) can achieve long-term remission in patients with allergic rhinitis (AR) through complex and still unknown mechanisms. The aim of this study is to evaluate the effect of SCIT over CD16 and CD16 monocytes, myeloid (mDCs) and plasmacytoid dendritic cells (pDCs) in patients with AR, comparatively to pharmacological standard treatment (non-SIT).
The relative frequency and absolute number of monocytes and DC subsets, the frequency of these cells producing TNFα after in vitro stimulation with (Dpt) extract, and the expression levels of receptor-bound IgE or IgG were assessed by flow cytometry, in peripheral blood samples from 23 healthy individuals (HG) and 43 participants with AR mono-sensitized to Dpt; 10 with non-SIT treatment and 33 under SCIT, just before (SCIT-T0) and 4 h after administration (SCIT-T4). Moreover, IFNα mRNA expression was evaluated in purified pDCs, by qRT-PCR.
After SCIT administration we observed a strong decrease of circulating pDCs, although accompanied by higher levels of IFNα mRNA expression, and an increase of circulating CD16 monocytes. AR participants under SCIT exhibited a higher expression of receptor-bound IgE in all cell populations that expressed the high affinity receptor for IgE (FcεRI) and a higher frequency of CD16 monocytes producing TNFα. Conversely, we observed a decrease in the frequency of mDCs producing TNFα in AR under SCIT, similar to the observed in the control group.
SCIT seems to induce numeric, phenotypic, and functional changes in circulating monocytes and dendritic cells, contributing at least in part to the well described immunological alterations induced by this type of immunotherapy.
特异性皮下免疫疗法(SCIT)可通过复杂且尚不清楚的机制使过敏性鼻炎(AR)患者实现长期缓解。本研究旨在评估SCIT对AR患者CD16和CD16单核细胞、髓样树突状细胞(mDCs)和浆细胞样树突状细胞(pDCs)的影响,并与药理学标准治疗(非特异性免疫疗法)进行比较。
通过流式细胞术评估23名健康个体(HG)和43名单纯对百日咳毒素(Dpt)致敏的AR参与者外周血样本中单核细胞和树突状细胞亚群的相对频率和绝对数量、这些细胞在用Dpt提取物体外刺激后产生肿瘤坏死因子α(TNFα)的频率,以及受体结合型IgE或IgG的表达水平;其中10名接受非特异性免疫疗法治疗,33名接受SCIT治疗,分别在给药前(SCIT-T0)和给药后4小时(SCIT-T4)进行检测。此外,通过定量逆转录聚合酶链反应(qRT-PCR)评估纯化的pDCs中干扰素α(IFNα)mRNA的表达。
SCIT给药后,我们观察到循环pDCs显著减少,尽管同时伴有IFNα mRNA表达水平升高,以及循环CD16单核细胞增加。接受SCIT治疗的AR参与者在所有表达IgE高亲和力受体(FcεRI)的细胞群体中,受体结合型IgE的表达更高,且产生TNFα的CD16单核细胞频率更高。相反,我们观察到接受SCIT治疗的AR患者中产生TNFα的mDCs频率降低,与对照组观察到的情况相似。
SCIT似乎会诱导循环单核细胞和树突状细胞发生数量、表型和功能变化,这至少部分促成了这类免疫疗法所引发的、已被充分描述的免疫改变。