Dai Shi-Xue, Gu Hong-Xiang, Lin Qian-Yi, Huang Shao-Zhuo, Xing Tiao-Si, Zhang Qing-Fang, Wu Gang, Chen Min-Hua, Tan Wan-Er, Jian Hong-Jian, Zheng Zhong-Wen, Zhong Tao, Zhang Min-Hai, Cheng Xing-Fang, Huang Peng, Liao Guang-Jie, Sha Wei-Hong
Department of Gastroenterology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, South China University of Technology, Guangzhou, Guangdong 510080, China.
Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Clin Res Hepatol Gastroenterol. 2017 Dec;41(6):693-702. doi: 10.1016/j.clinre.2017.03.009. Epub 2017 May 10.
BACKGROUND/AIM: The balance of blood CD8CD28/CD8CD28 T cells has been verified to be vital for patients with ulcerative colitis (UC), but their role in inflammatory bowel disease (IBD) remains unknown. This investigation aimed to evaluate the efficiency of the balance in predicting the active stage in IBD patients.
Fifty-three IBD subjects, including 31 UC and 22 Crohn's disease (CD) patients, were enrolled, and their peripheral blood CD8CD28 and CD8CD28 T cell levels were tested using flow cytometry. The risk factors related to prognosis were compared between UC and CD patients. A 1-year follow-up was performed for all the IBD patients, and the CD8 T cells and their ratio were compared at the 3rd, 6th, 9th, and 12th months during follow-up. The sensitivity and specificity of the CD8 T cell level and balance were analyzed through receiver operator characteristic (ROC) curves. The cumulative remission lasting rates (CRLRs) under the different factors were analyzed using the Kaplan-Meier method.
Higher prescription rates of immunosuppressants, steroids, probiotics, and biological agents (BAs) were found in CD subjects in comparison to UC subjects (P=0.005, 0.024, 0.034, and 0.001), as was a higher active rate during follow-up (95.5% of CD patients vs 67.7% of UC patients, P=0.035). The CD8CD28 T cell level and the CD8CD28/CD8CD28 T cell ratio were significantly higher in UC patients than in CD patients, but the reverse was true for CD8CD28 T cells during follow-up at the 9th and 12th month (all P<0.05). The diagnostic models of the initial CD8CD28 and CD8CD28 T cell numbers and the CD8CD28/CD8CD28 T cell ratio in predicting the active stage were found to be significant, with areas under the curves (AUCs) of 0.883, 0.098, and 0.913 for UC subjects (with 95% CI: 0.709-0.940, 0.009-0.188, and 0.842-1.003; P=0.001, 0.00, and 0.000) and 0.812, 0.078, and 0.898 for CD subjects (with 95% CI: 0.683-0.957, 0.003-0.158, and 0.837-0.998; P=0.003, 0.00, and 0.000). The cut-off values showed that when the ratios were 1.30 for UC and 1.22 for CD patients, the best sensitivity and specificity were observed, with 91.6% and 89.0% for UC and 88.5% and 85.1% for CD, respectively. The CRLRs were significantly higher in female, non-BA-treated, non-surgical IBD subjects when compared to male, BA-treated, surgical subjects (P=0.031, 0.000, and 0.000). The number of CD8CD28 and CD8CD28 T cells and the CD8CD28/CD8CD28 T cell ratio were correlated with BA treatment and surgery (all P<0.05).
The CD8CD28/CD8CD28 T cell balance, expected to be a novel immunologic marker, presented a satisfactory efficiency with high sensitivity and specificity in predicting the active stage in UC and CD patients, and the balance was closely related to the use of BAs and surgery.
背景/目的:血液中CD8CD28⁺/CD8CD28⁻ T细胞平衡已被证实对溃疡性结肠炎(UC)患者至关重要,但其在炎症性肠病(IBD)中的作用尚不清楚。本研究旨在评估该平衡在预测IBD患者活动期方面的效能。
纳入53例IBD患者,其中包括31例UC患者和22例克罗恩病(CD)患者,采用流式细胞术检测其外周血CD8CD28⁺和CD8CD28⁻ T细胞水平。比较UC和CD患者与预后相关的危险因素。对所有IBD患者进行1年随访,比较随访期间第3、6、9和12个月的CD8⁺ T细胞及其比例。通过受试者工作特征(ROC)曲线分析CD8⁺ T细胞水平和平衡的敏感性和特异性。采用Kaplan-Meier法分析不同因素下的累积缓解持续率(CRLR)。
与UC患者相比,CD患者使用免疫抑制剂、类固醇、益生菌和生物制剂(BAs)的处方率更高(P = 0.005、0.024、0.034和0.001),随访期间的活动率也更高(95.5%的CD患者 vs 67.7%的UC患者,P = 0.035)。UC患者的CD8CD28⁺ T细胞水平和CD8CD28⁺/CD8CD28⁻ T细胞比例显著高于CD患者,但在随访第9个月和第12个月时,CD8CD28⁻ T细胞情况相反(均P<0.05)。初始CD8CD28⁺和CD8CD28⁻ T细胞数量以及CD8CD28⁺/CD8CD28⁻ T细胞比例预测活动期的诊断模型具有显著性,UC患者的曲线下面积(AUC)分别为0.883, 0.098, 和0.913(95% CI:0.709 - 0.940, 0.009 - 0.188, 和0.842 - 1.003;P = 0.001, 0.00, 和0.000),CD患者分别为0.812, 0.078, 和0.898(95% CI:0.683 - 0.957, 0.003 - 0.158, 和0.837 - 0.998;P = 0.003, 0.00, 和0.000)。截断值显示,当UC患者比例为1.30且CD患者比例为1.22时,观察到最佳敏感性和特异性,UC患者分别为91.6%和89.0%,CD患者分别为88.5%和85.1%。与男性、接受BA治疗、接受手术的IBD患者相比, 女性、未接受BA治疗、未接受手术的IBD患者的CRLR显著更高(P = 0.031、0.000和0.000)。CD8CD28⁺和CD8CD28⁻ T细胞数量以及CD8CD28⁺/CD8CD28⁻ T细胞比例与BA治疗和手术相关(均P<0.05)。
CD8CD28⁺/CD8CD28⁻ T细胞平衡有望成为一种新的免疫标志物,在预测UC和CD患者活动期方面具有较高的敏感性和特异性,且该平衡与BA的使用和手术密切相关。