T and B Lymphocyte Transcriptional States Differentiate between Sensitized and Unsensitized Individuals in Alpha-Gal Syndrome.
T and B Lymphocyte Transcriptional States Differentiate between Sensitized and Unsensitized Individuals in Alpha-Gal Syndrome.
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DOI：
10.3390/ijms22063185
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发表时间：
2021-03-20
影响因子：
5.6
通讯作者：
Commins SP
中科院分区：
文献类型：
--
作者：
Iweala OI;Choudhary SK;Addison CT;Commins SP
阿尔法-半乳糖综合征(AGS)的发病机制尚不完全清楚。AGS个体和非过敏性对照之间免疫基因表达的差异可能阐明AGS发生的关键分子途径和靶点。我们用来自7名对照组、15名AGS参与者和2名对α-Gal致敏但不过敏的参与者的外周血单核细胞(PBMC)的RNA进行了免疫表达谱分析，该面板包括来自14种不同细胞类型的770个基因。受试者和对照组之间差异表达最多的基因包括调节免疫基因表达的转录因子，如核因子κB途径(NFKBIA、NFKB2、REL)、抗原提呈分子、2型/变态反应性免疫反应、瘙痒和过敏性皮炎。与T和B细胞功能相关的差异表达基因还包括转录因子bCL-6、抗原经验标记(CD44)和记忆标记(CD27)、趋化因子受体(CXCR3、CXCR6)以及B细胞增殖、细胞周期进入和免疫球蛋白产生的调节因子(CD70)。AGS患者的PBMC与对照组相比，其肿瘤坏死因子和干扰素-γ的mRNA表达也增加。AGS与外周血单核细胞中不同的基因表达谱有关。与抗原提呈、经历抗原的T细胞和2型免疫反应相关的DEGS可能促进α-Gal特异性IgE的形成和AGS的维持。
The mechanisms of pathogenesis driving alpha-gal syndrome (AGS) are not fully understood. Differences in immune gene expression between AGS individuals and non-allergic controls may illuminate molecular pathways and targets critical for AGS development. We performed immune expression profiling with RNA from the peripheral blood mononuclear cells (PBMCs) of seven controls, 15 AGS participants, and two participants sensitized but not allergic to alpha-gal using the NanoString nCounter PanCancer immune profiling panel, which includes 770 genes from 14 different cell types. The top differentially expressed genes (DEG) between AGS subjects and controls included transcription factors regulating immune gene expression, such as the NFκB pathway (NFKBIA, NFKB2, REL), antigen presentation molecules, type 2/allergic immune responses, itch, and allergic dermatitis. The differential expression of genes linked to T and B cell function was also identified, including transcription factor BCL-6, markers of antigen experience (CD44) and memory (CD27), chemokine receptors (CXCR3, CXCR6), and regulators of B-cell proliferation, cell cycle entry and immunoglobulin production (CD70). The PBMCs from AGS subjects also had increased TNF and IFN-gamma mRNA expression compared to controls. AGS is associated with a distinct gene expression profile in circulating PBMCs. DEGs related to antigen presentation, antigen-experienced T-cells, and type 2 immune responses may promote the development of alpha-gal specific IgE and the maintenance of AGS.
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影响因子：
7.3
作者：
Bacalao MA;Satterthwaite AB
通讯作者：
Satterthwaite AB
DOI：
10.1016/j.bbrc.2005.07.019
发表时间：
2005-09-09
影响因子：
3.1
作者：
Cheong, HS;Park, CS;Oh, B
通讯作者：
Oh, B
DOI：
10.1016/j.jaci.2011.02.019
发表时间：
2011-05
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Commins SP;James HR;Kelly LA;Pochan SL;Workman LJ;Perzanowski MS;Kocan KM;Fahy JV;Nganga LW;Ronmark E;Cooper PJ;Platts-Mills TA
通讯作者：
Platts-Mills TA
影响因子：
6.4
作者：
Ferreira, BR;Silva, JS
通讯作者：
Silva, JS
影响因子：
12.4
作者：
Hamsten, C.;Starkhammar, M.;van Hage, M.
通讯作者：
van Hage, M.