Barrenäs Fredrik, Andersson Bengt, Cardell Lars Olaf, Langston Michael, Mobini Reza, Perkins Andy, Soini Juhani, Ståhl Arne, Benson Mikael
The Unit for Clinical Systems Biology, Department of Pediatrics, The Queen Silvia Children's Hospital, SE 41685 Göteborg, Sweden.
Cytokine. 2008 Jun;42(3):325-9. doi: 10.1016/j.cyto.2008.03.004. Epub 2008 Apr 25.
In model organisms, thousands of genes differ in expression between females and males. It is not known if differences on a similar scale are found in humans nor how this relates to disease. However, in allergic disease gender differences in the levels of both inflammatory cells and proteins have been shown. In this study, we found lower nasal fluid allergen-specific IgE in women than men with seasonal allergic rhinitis (SAR). This led to genome-wide analyses of gene expression in allergen-challenged CD4(+) cells from patients with SAR before and after treatment with cortisone. Before treatment, 975 genes differed in expression between women and men: 337 were higher in women. After treatment only 428 genes and one pathway differed in expression. The genes that differed in expression between women and men were over-represented in 10 pathways. Five of the pathways regulated chemotaxis. All five were less active in women. One of the pathways was induced by the eosinophilic chemokine CCL4. Analysis of nasal fluid CCL4 protein confirmed lower levels in women with seasonal allergic rhinitis, before and during the pollen season. By contrast, nasal fluid CCL3 levels did not differ between the genders. In summary, this study shows gender differences in specific inflammatory pathways and proteins in patients with seasonal allergic rhinitis. Further studies are warranted to examine if such differences have diagnostic and therapeutic implications in allergic diseases.
在模式生物中，数千个基因在雌性和雄性之间存在表达差异。目前尚不清楚在人类中是否也存在类似规模的差异，以及这与疾病有何关联。然而，在过敏性疾病中，炎症细胞和蛋白质水平的性别差异已得到证实。在本研究中，我们发现季节性变应性鼻炎（SAR）女性患者的鼻分泌物变应原特异性IgE水平低于男性。这促使我们对接受可的松治疗前后的SAR患者变应原激发的CD4(+)细胞进行全基因组基因表达分析。治疗前，975个基因在女性和男性之间存在表达差异：337个基因在女性中表达较高。治疗后，只有428个基因和一条信号通路存在表达差异。在女性和男性之间存在表达差异的基因在10条信号通路中过度富集。其中5条信号通路调节趋化作用。所有这5条信号通路在女性中活性较低。其中一条信号通路由嗜酸性粒细胞趋化因子CCL4诱导。对鼻分泌物CCL4蛋白的分析证实，季节性变应性鼻炎女性患者在花粉季节之前和期间的CCL4水平较低。相比之下，鼻分泌物CCL3水平在两性之间没有差异。总之，本研究显示了季节性变应性鼻炎患者在特定炎症信号通路和蛋白质方面的性别差异。有必要进一步研究这些差异在过敏性疾病中是否具有诊断和治疗意义。
