| Objective:Ulcerative colitis(UC)is considered an immune disorder-mediated chronic inflammatory disease of the intestinal tract.The dysregulated T-lymphocyte response with abnormal development of T-lymphocyte subsets plays an important role in the pathogenesis of UC.The association between T-lymphocyte subsets,disease severity and clinical outcomes in UC patients are still not clearly.The aim of this study was to explore the compositional changes of peripheral blood T-lymphocyte subsets and evaluate the predictive value of T-lymphocyte subsets on disease severity and clinical outcomes in UC patients.Methods:This study was a retrospective case-control study,which included 116 patients with confirmed diagnoses of UC and 90 randomly selected healthy controls(HC)admitted to the Affiliated Hospital of Qingdao University from January 2018 to December 2021.The UC patients included were divided into mild-moderate UC group and severe UC group according to the clinical disease severity which was assessed by the Mayo score.The endoscopic activity of UC patients was evaluated by the Ulcerative Colitis Endoscopic Index of Severity(UCEIS).The disease extent of UC patients was assessed using the Montreal classification.Participants were followed up for 180 days and whether they underwent UC-related readmission due to recurrence or surgery due to failure of medical therapy during the follow up were recorded.The laboratory indexes including T-lymphocyte subsets,C-reactive protein(CRP)and erythrocyte sedimentation rate(ESR)of patients in each group were retrospectively analyzed.T-test and chi-square test were used to compare the differences of indicators in each group and the changes of peripheral blood T-lymphocyte subsets in UC patients.Spearman’s correlation analysis was used to analyze the association between T-lymphocyte subsets,the Mayo score and UCEIS.By drawing receiver operating characteristic(ROC)curve and calculating the area under the curve,cut-off value,sensitivity and specificity to evaluate the predictive value of T-lymphocyte subsets on disease severity and clinical outcomes in UC patients.Cox proportional hazard regression analysis and cumulative survival analysis were used to determine the independent risk factors for UC-related readmission and surgery and the correlation between T-lymphocyte subsets and clinical outcomes.Results:1.A total of 116 UC patients with active disease and 90 HC were included.The mean age of UC patients was 46.75±16.47 years,including 69 male(59.48%)and 47female(40.52%).There were 78 cases(67.24%)in mild-moderate group and 38 cases(32.76%)in severe group.The mean age of healthy control was 50.06±10.09 years,including 48 male(53.33%)and 42 female(46.67%).There was no statistical difference in gender and age between UC patients and HC.2.Compared with HC,the proportion of CD4~+T cells(42.85%±9.77%vs45.71%±7.94%,P=0.021)and CD4~+/CD8~+ratio(1.75±0.81 vs 2.00±0.77,P=0.025)was significantly lower,whereas the percentage of CD8~+T cells(27.88%±8.86%vs25.00%±6.47%,P=0.008)was higher in UC patients.The severe group had lower proportion of CD4~+T cells(40.40%±9.36%vs 45.71%±7.94%,P=0.01)and CD4~+/CD8~+ratio(1.43±0.61 vs 2.00±0.77,P<0.001),whereas higher proportion of CD3~+HLA-DR~+T cells(8.83%±6.55%vs 4.60±2.56,P<0.001)and CD8~+T cells(31.36%±8.49%vs 25.00%±6.47%,P<0.001)than HC.There was only the difference of CD3~+HLA-DR~+T cells(3.46%±3.82%vs 4.60%±2.56%,P=0.024)in the mild-moderate group,compared with HC.The severe group had higher percentage of CD8~+T cells(31.36%±8.49%vs 26.18%±8.59%,P=0.003)and CD3~+HLA-DR~+T cells(8.83%±6.55%vs 3.46%±3.82%,P<0.001)and with lower CD4~+/CD8~+ratio(1.43±0.61vs 1.91±0.85,P=0.001)than the mild-moderate group.3.Spearman’s correlation analysis showed that both Mayo score and UCEIS showed positive correlation with the proportion of CD3~+HLA-DR~+T cells(r=0.535,P<0.001; r=0.691,P<0.001),and negative correlation with the proportion of CD4~+CD25~+T cells(r=-0.296,P=0.001;r=-0.271,P=0.003).4.ROC curve analysis showed that the AUC of CD3~+HLA-DR~+T cells,CD8~+T cells,CD4~+/CD8~+ratio and CD4~+CD25~+T cells for predicting severe UC was 0.885,0.677,0.669 and 0.631,with the cut-off value of 5.33%,27.03%,1.73 and 3.05%,respectively.The AUC of CRP and ESR for predicting severe UC was 0.878 and 0.797,with the cut-off value of 9.30 mg/L and 16.5 mm/h.The combination of CD3~+HLA-DR~+T cells and CRP had stronger predictive value for severe UC with AUC of 0.929,sensitivity of89.47%and specificity of 85.90%.5.There were 24 patients underwent UC-related readmission due to recurrence or surgery due to failure of medical therapy during the follow-up of 180 days.The patients experiencing UC-related readmission or surgery had higher baseline proportion of CD3~+HLA-DR~+T cells(10.36%±9.42%vs 3.88%±2.57%,P=0.003)and CD8~+T cells(31.19%±10.59%vs 27.01%±8.20%,P=0.039).The proportion of CD3~+HLA-DR~+T cells was the independent risk factor of UC-related readmission or surgery(HR=1.109,P=0.002).ROC curve showed that the AUC of CD3~+HLA-DR~+T cells for predicting readmission or surgery was 0.796 with the cut-off value of 5.38%,sensitivity of 75.00%and specificity of 80.43%.Cumulative survival analysis showed that UC patients with CD3~+HLA-DR~+T cells proportion>5.38%had a shorter time to readmission or surgery(145 days vs 175 days,P<0.001).Conclusion:1.There were dysregulated peripheral blood T-lymphocyte subsets in UC patients.This disorder was more pronounced in severely active UC patients.2.The proportion of CD3~+HLA-DR~+T cells was positively correlated with the clinical disease severity and the endoscopic activity of UC patients.The proportion of CD4~+CD25~+T cells was negatively correlated with the clinical disease severity and the endoscopic activity of UC patients.3.Peripheral blood CD3~+HLA-DR~+T cells>5.33%,CD8~+T cells>27.03%,CD4~+/CD8~+ratio<1.73 and CD4~+CD25~+T cells<3.05%had a certain predictive value for severe UC.Meanwhile,the predictive efficacy of CD3~+HLA-DR~+T cells for severe UC was higher than CRP and ESR levels.The combination of CD3~+HLA-DR~+T cells and CRP had stronger predictive value for severe UC.4.The clinical outcomes of UC patients with CD3~+HLA-DR~+T cells>5.38%may be poor. |
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