Saidova Aziza, Bublin Merima, Schmidthaler Klara, Fajgelj Veronika, Klinglmueller Florian, Spittler Andreas, Hafner Christine, Szépfalusi Zsolt, Breiteneder Heimo, Eiwegger Thomas
Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
Department of Hospital Pediatrics 1, Clinical Allergology, Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan.
Int Arch Allergy Immunol. 2019;179(1):10-16. doi: 10.1159/000496438. Epub 2019 Mar 20.
Peanut allergy is considered to be the most common cause for food-induced anaphylaxis. Currently, no approved treatment is available. Avoidance is the only measure to prevent anaphylactic reactions to peanuts. T-helper cells are of special importance for the sensitization process and the maintenance of allergic inflammation. Identifying markers of allergen-specific T-cell responses may help to develop novel treatment approaches. Therefore, we aimed to define new T-cell target genes in Ara h 2-specific T cells and to investigate the possibility of using them as biomarkers of peanut allergy in peripheral blood mononuclear cells (PBMCs). We performed whole mRNA array analysis (whole human genome oligo microarray) of in vitro expanded Ara h 2-specific T cells (CFSElowCD3+CD4+) from 5 peanut-allergic (PA) and 5 non-peanut-sensitized individuals. Expression of selected genes as a result of a two-step bioinformatic approach was confirmed in a second cohort by quantitative PCR. TGF-β- activated kinase 1 and MAP3K7 binding protein 3 (TAB3), calcium/calmodulin-dependent protein kinase type IV (CAMK4) and HemK methyltransferase family member 1 (HEMK1) were significantly upregulated in Ara h 2-specific T cells of PA patients. In addition, the expression of these genes was also assessed in unstimulated PBMCs from a cohort (n = 43) of PA, atopic non-PA, and nonatopic controls. Interestingly, in unstimulated PBMCs, TAB3 expression was significantly downregulated in PA patients compared to atopic non-PA individuals. Thus, TAB3 may play a significant role at the level of T-cell activation and may also be a candidate biomarker for PA.
花生过敏被认为是食物诱导的过敏反应最常见的原因。目前，尚无获批的治疗方法。避免接触是预防花生过敏反应的唯一措施。辅助性T细胞在致敏过程和过敏性炎症的维持中具有特殊重要性。识别过敏原特异性T细胞反应的标志物可能有助于开发新的治疗方法。因此，我们旨在确定Ara h 2特异性T细胞中新的T细胞靶基因，并研究将它们用作外周血单个核细胞（PBMC）中花生过敏生物标志物的可能性。我们对来自5名花生过敏（PA）个体和5名非花生致敏个体的体外扩增的Ara h 2特异性T细胞（CFSElowCD3+CD4+）进行了全mRNA阵列分析（全人类基因组寡核苷酸微阵列）。通过两步生物信息学方法筛选出的基因表达，在第二个队列中通过定量PCR得到了证实。转化生长因子-β激活激酶1和MAP3K7结合蛋白3（TAB3）、钙/钙调蛋白依赖性蛋白激酶IV型（CAMK4）和HemK甲基转移酶家族成员1（HEMK1）在PA患者的Ara h 2特异性T细胞中显著上调。此外，还在来自PA患者、特应性非PA患者和非特应性对照的一个队列（n = 43）的未刺激PBMC中评估了这些基因的表达。有趣的是，在未刺激的PBMC中，与特应性非PA个体相比PA患者的TAB3表达显著下调。因此，TAB3可能在T细胞激活水平上发挥重要作用，也可能是PA的候选生物标志物。
