Cairns Ewa, Saunders Sheri, Bell David A, Blackler Garth, Lac Patrick, Barra Lillian
Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada.
Department of Medicine/Rheumatology, The University of Western Ontario, London, ON, Canada.
J Transl Autoimmun. 2020 Apr 10;3:100053. doi: 10.1016/j.jtauto.2020.100053. eCollection 2020.
Rheumatoid Arthritis (RA) is more common and severe in women compared to men. Both women and men with RA express autoantibodies to post-translationally modified antigens, including citrullinated and homocitrullinated proteins or peptides. These autoantibodies are strongly linked with the HLA-DR4 gene. The objective of this study was to determine sex differences in immune responses to homocitrullinated antigens. We used a humanized animal model of RA, DR4-transgenic mice and immunized them with a homocitrullinated peptide called HomoCitJED. Immune responses in these mice were measured for splenocyte proliferation by tritiated thymidine incorporation, serum autoantibody production by ELISA and cytokine levels by multiplex. We found that T cell and antibody responses to homocitrullinated antigens were similar in male and female mice. However, we found sex differences in serum cytokine profiles with female mice having higher ratio of IL-1α to IL-5, suggesting imbalances in immune regulation. This is the first study to report that immune responses to homocitrullinated antigens can be differentiated by sex.
与男性相比，类风湿性关节炎（RA）在女性中更为常见且病情更严重。患有RA的女性和男性都会对翻译后修饰的抗原产生自身抗体，包括瓜氨酸化和高瓜氨酸化的蛋白质或肽段。这些自身抗体与HLA - DR4基因密切相关。本研究的目的是确定对高瓜氨酸化抗原的免疫反应中的性别差异。我们使用了一种RA的人源化动物模型——DR4转基因小鼠，并用一种名为HomoCitJED的高瓜氨酸化肽对其进行免疫。通过氚标记胸腺嘧啶核苷掺入法测量这些小鼠脾细胞增殖来检测免疫反应，通过ELISA检测血清自身抗体产生情况，并通过多重检测法检测细胞因子水平。我们发现，雄性和雌性小鼠对高瓜氨酸化抗原的T细胞和抗体反应相似。然而，我们发现血清细胞因子谱存在性别差异，雌性小鼠的IL - 1α与IL - 5比值更高，这表明免疫调节存在失衡。这是第一项报道对高瓜氨酸化抗原的免疫反应可因性别而异的研究。
