TIGIT signalling pathway negatively regulates CD4+ T-cell responses in systemic lupus erythematosus.

B-lymphocyte hyperactivity in systemic lupus erythematosus (SLE) is T-cell-dependent, and CD4+ T-cell activation is essential to SLE pathogenesis. However, the mechanism of the deregulation of CD4+ T cells in SLE is largely unknown. T-cell immunoglobulin and ITIM domain (TIGIT) is a new inhibitory receptor preferentially expressed on activated CD4+ T cells. Here, we address the role of TIGIT in the pathogenesis of SLE. Our results showed that TIGIT expression on CD4+ T cells was significantly elevated in patients with SLE and highly correlated with the activity of the disease. TIGIT+ CD4+ T cells from both healthy individuals and patients with SLE had a more activated phenotype than TIGIT- CD4+ T cells. In contrast, the activation, proliferation and cytokine production potential of TIGIT+ CD4+ T cells were significantly lower than those of TIGIT- CD4+ T cells. Furthermore, activation of the TIGIT pathway by using CD155 could substantially down-regulate the activities of CD4+ T cells from SLE patients in vitro, and in vivo administration of CD155 resulted in a delayed development of SLE in MRL/lpr mice. TIGIT is a powerful negative regulator of CD4+ T cells in SLE, which suggests that the TIGIT signalling pathway may be used as a potential therapeutic target for treating this disease.

Establishment of the Reference Intervals of Lymphocyte Function in Healthy Adults Based on IFN-γ Secretion Assay upon Phorbol-12-Myristate-13-Acetate/Ionomycin Stimulation.

The function of lymphocytes is the key to reflect the immune status of hosts. Evaluation of lymphocyte function is a useful tool to monitor the effect of immunosuppressive treatment and predict the prognosis of immune-mediated diseases (e.g., cancer, autoimmune diseases, and infectious diseases). As the lymphocytes have various activities, such as activation, cytotoxicity, and cytokine secretion, it is a challenge to evaluate the function of lymphocytes in clinical practice and the reference intervals (RIs) of lymphocyte function are rarely reported. The present study showed that the secretion of IFN-γ was well correlated with the activation, chemotaxis, and cytotoxicity of CD4+, CD8+ T cells, and NK cells, which suggests that IFN-γ production can be used as a symbol of lymphocyte function. We therefore created a simple method to detect the function of CD4+, CD8+ T cells, and NK cells simultaneously according to IFN-γ secretion by using whole blood instead of peripheral blood mononuclear cells. We further established the RIs of lymphocyte function (CD4+ T cells: 15.31-34.98%; CD8+ T cells: 26.11-66.59%; NK cells: 39.43-70.79%) in healthy adults. This method showed good reproducibility for the evaluation of lymphocyte function. The established RIs were suitable for use in other centers based on the validation data. We also validated the RIs in individuals with different immune status, and the results showed that kidney transplant recipients and infants (0-1 year) had a decreased lymphocyte function, whereas T cells in systemic lupus erythematosus patients exhibited an opposite trend. Overall, we have successfully established the RIs of lymphocyte function in healthy adults in a simple way, which might be of important clinical value in the diagnosis, monitoring, and prognosis of immune-related diseases.

Diagnostic Performance of a 5-Marker Predictive Model for Differential Diagnosis Between Intestinal Tuberculosis and Crohn's Disease.

Background: The differentiation between intestinal tuberculosis (ITB) and Crohn's disease (CD) is a challenge. The aim of this study was to investigate a predictive model for differential diagnosis between ITB and CD. Methods: A total of 268 patients who were suspected of having ITB or CD were prospectively recruited between January 2013 and September 2016. The clinical, laboratory, radiological, endoscopic, and histological features were investigated and subjected to univariate and multivariate analyses. The final predictive model was developed based on the regression coefficients of multivariate logistic regression. To validate the model, the same regression equation was tested on the other group. Results: A total of 239 patients had a final diagnosis, including 86 ITB and 153 CD. Five variables (perianal disease, pulmonary involvement, longitudinal ulcer, left colon, and ratio of tuberculosis-specific antigen to phytohaemagglutinin) were selected for the predictive model to discriminate between ITB and CD. In the predictive model of the training data set, the area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, and accuracy, with a cutoff level of 0.29, were 0.975 (95% confidence interval [CI], 0.939-0.993), 96.7%, 90.7%, and 92.8%, respectively. Application of the predictive model to the validation data set showed similar performance in distinguishing ITB from CD. The area under the ROC curve, sensitivity, specificity, and accuracy were 0.950 (95% CI, 0.871-0.987), 88.5%, 93.5%, and 91.7%, respectively. Conclusions: This 5-marker predictive model could be conveniently used by clinicians to draw a reliable differential diagnosis between ITB and CD in clinical practice. 10.1093/ibd/izy154_video1izy154.video15790725497001.

The performance of the TBAg/PHA ratio in the diagnosis of active TB disease in immunocompromised patients.

OBJECTIVES: The results of the T-SPOT.TB (T-SPOT) assay are reduced in immunocompromised patients with active tuberculosis (ATB), and it is difficult using T-SPOT results to distinguish ATB from latent tuberculosis infection (LTBI) in this condition. The aim of this study was to determine the performance of the TBAg/PHA ratio in T-SPOT assay in the diagnosis of ATB in immunocompromised patients. METHODS: One hundred and forty three immunocompromised ATB patients and 124 LTBI individuals were diagnosed according to conventional tests and T-SPOT assay. RESULTS: The results of T-SPOT assay are of no value in the diagnosis of ATB in immunocompromised patients. However, the number of phytohaemagglutinin (PHA) spot-forming cells (sfc) in T-SPOT assay was substantially decreased in immunocompromised ATB patients compared with that in LTBI individuals. Receiver operating characteristic (ROC) analysis revealed that a further calculation of the TBAg/PHA ratio (the larger of the ESAT-6/PHA and CFP-10/PHA) showed a better performance in distinguishing these two diseases. Using the threshold value of 0.316, the sensitivity and specificity for distinguishing immunocompromised ATB patients from LTBI individuals were respectively 79.21 and 94.05%. CONCLUSIONS: Our findings suggest that the TBAg/PHA ratio might have some significance for the diagnosis of TB disease in immunocompromised patients.