CD8+CD28+/CD8+CD28- T cell equilibrium can predict the active stage for patients with inflammatory bowel disease

Abstract

Background/aim: The balance of blood CD8⁺CD28⁺/CD8⁺CD28^- 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.

Methods: Fifty-three IBD subjects, including 31 UC and 22 Crohn's disease (CD) patients, were enrolled, and their peripheral blood CD8⁺CD28⁺ and CD8⁺CD28^- 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.

Results: 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 CD8⁺CD28⁺ T cell level and the CD8⁺CD28⁺/CD8⁺CD28^- T cell ratio were significantly higher in UC patients than in CD patients, but the reverse was true for CD8⁺CD28^- T cells during follow-up at the 9th and 12th month (all P<0.05). The diagnostic models of the initial CD8⁺CD28⁺ and CD8⁺CD28^- T cell numbers and the CD8⁺CD28⁺/CD8⁺CD28^- 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 CD8⁺CD28⁺ and CD8⁺CD28^- T cells and the CD8⁺CD28⁺/CD8⁺CD28^- T cell ratio were correlated with BA treatment and surgery (all P<0.05).

Conclusion: The CD8⁺CD28⁺/CD8⁺CD28^- 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.

Keywords: Active stage; CD8+ T cells; Immunologic balance; Inflammatory bowel disease; Lasting time of remission.