Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brazil.
Universidade Vale do Rio Doce - Univale, Department of Health Sciences, Governador Valadares, MG, Brazil.
Front Immunol. 2023 Apr 28;14:1130137. doi: 10.3389/fimmu.2023.1130137. eCollection 2023.
The aim of the present study was to investigate the association between the single nucleotide polymorphism (SNP) rs1927914 A/G in gene and the immunological profile of household contacts (HHC) of leprosy patients. Leprosy classification is usually complex and requires the assessment of several clinical and laboratorial features.
Herein, we have applied distinct models of descriptive analysis to explore qualitative/quantitative changes in chemokine and cytokine production in HHC further categorized according to operational classification [HHC(PB) and HHC(MB)] and according to SNP.
Our results showed that stimuli induced an outstanding production of chemokines (CXCL8;CCL2; CXCL9; CXCL10) by HHC(PB), while increase levels of pro-inflammatory cytokines (IL-6; TNF; IFN-γ; IL-17) were observed for HHC(MB). Moreover, the analysis of chemokine and cytokine signatures demonstrated that A allele was associated with a prominent soluble mediator secretion (CXCL8; CXCL9; IL-6; TNF; IFN-γ). Data analysis according to SNP genotypes further demonstrated that AA and AG were associated with a more prominent secretion of soluble mediators as compared to GG, supporting the clustering of AA and AG genotypes into dominant genetic model. CXCL8, IL-6, TNF and IL-17 displayed distinct profiles in HHC(PB) HHC(MB) or AA+AG GG genotype. In general, chemokine/cytokine networks analysis showed an overall profile of AA+GA-selective (CXCL9-CXCL10) and GG-selective (CXCL10-IL-6) axis regardless of the operational classification. However, mirrored inverted CCL2-IL-10 axis and a (IFN-γ-IL-2)-selective axis were identified in HHC(MB). CXCL8 presented outstanding performance to classify AA+AG from GG genotypes and HHC(PB) from HHC(MB). TNF and IL-17 presented elevated accuracy to classify AA+AG from GG genotypes and HHC(PB) (low levels) from HHC(MB) (high levels), respectively. Our results highlighted that both factors: i) differential exposure to and ii) rs1927914 genetic background impact the immune response of HHC. Our main results reinforce the relevance of integrated studies of immunological and genetic biomarkers that may have implications to improve the classification and monitoring of HHC in future studies.
本研究旨在探讨麻风病患者家庭接触者（HHC）中基因单核苷酸多态性（SNP）rs1927914A/G 与免疫谱之间的关系。麻风病的分类通常很复杂，需要评估几个临床和实验室特征。
在此，我们应用了不同的描述性分析模型，以进一步探讨根据操作性分类[HHC（PB）和 HHC（MB）]和根据 SNP 对 HHC 中趋化因子和细胞因子产生的定性/定量变化进行分类。
我们的结果表明，刺激物诱导 HHC（PB）产生出色的趋化因子（CXCL8；CCL2；CXCL9；CXCL10）产生，而 HHC（MB）则观察到促炎细胞因子（IL-6；TNF；IFN-γ；IL-17）水平升高。此外，趋化因子和细胞因子特征的分析表明，A 等位基因与可溶性介质的显著分泌有关（CXCL8；CXCL9；IL-6；TNF；IFN-γ）。根据 SNP 基因型进行数据分析进一步表明，与 GG 相比，AA 和 AG 与更显著的可溶性介质分泌相关，支持将 AA 和 AG 基因型聚类为显性遗传模型。与 GG 基因型相比，HHC（PB）或 AA+AG 与 HHC（MB）或 AA+AG 与 GG 基因型相比，CXCL8、IL-6、TNF 和 IL-17 显示出不同的特征谱。一般来说，趋化因子/细胞因子网络分析显示出 AA+GA-选择性（CXCL9-CXCL10）和 GG-选择性（CXCL10-IL-6）轴的总体特征，而与操作性分类无关。然而，在 HHC（MB）中鉴定出了镜像倒置的 CCL2-IL-10 轴和（IFN-γ-IL-2）-选择性轴。CXCL8 表现出出色的性能，可将 AA+AG 与 GG 基因型和 HHC（PB）与 HHC（MB）区分开来。TNF 和 IL-17 分别表现出较高的准确性，可将 AA+AG 与 GG 基因型和 HHC（PB）（低水平）与 HHC（MB）（高水平）区分开来。我们的结果强调了两个因素：i）对 的不同暴露，ii） rs1927914 遗传背景对 HHC 的免疫反应有影响。我们的主要结果强调了免疫和遗传生物标志物综合研究的重要性，这可能对未来研究中改善 HHC 的分类和监测具有重要意义。
