COMBINATION OF T-SPOT.TB RATIO AND EXPRESSION OF CD161 ON T LYMPHOCYTES IN DISCRIMINATING ACTIVE TB AND LATENT TB INFECTION

Abstract

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Interferon-gamma releasing assay using qualitative T-SPOT.TB cannot discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). Previous research suggests that interleukin-17 secreting from CD161-expressing T-lymphocytes is low in patients developing ATB. This study aims to investigate the performance of quantitative T-SPOT.TB alone and in combination with CD161-expressing T-lymphocytes in differentiating ATB from LTBI. METHODS: This cross-sectional study was conducted in a university hospital between January 2020 and December 2020. Enrolled subjects were categorized as the following: (i) newly microbiologically confirmed pulmonary TB (ATB), (ii) close-contacts with normal chest radiograph and positive qualitative T-SPOT.TB (LTBI), and (iii) negative T-SPOT.TB (control). All subjects underwent quantitative measurement for the ratio of TB-specific antigen spots over positive control-PHA spots (TBAg/PHA), and flow cytometry for CD161-expressing T-lymphocytes (index-CD161 calculated using the lymphocyte to monocyte ratio multiplied by the percentage of CD161+ expression on CD8+ T-lymphocyte). The group comparisons were made and the cutoff values for TBAg/PHA ratio alone and combined with index-CD161 were determined for the sensitivity, specificity, and area under the receiver operating characteristics curve (AUROC). RESULTS: A total of 113 subjects were enrolled (36 active TB, 18 LTBI, and 59 control). The TBAg/PHA ratio was significantly higher in the ATB group than in the LTBI and control groups (p<0.001). The index-CD161 was significantly lower in the ATB group than in the LTBI and control groups (p<0.001). Using the TBAg/PHA ratio value of ≥ 0.039, the sensitivity, specificity and AUROC were 72%, 72% and 0.76, respectively. When the index-CD161 value of ≤ 145 was analyzed with the TBAg/PHA ratio in logistic regression model, the diagnostic performance of ATB was improved by increasing the sensitivity, specificity and AUROC to 88%, 93% and 0.95, respectively. CONCLUSIONS: Combination of TBAg/PHA ratio in the T-SPOT.TB test with CD161 expressing T-lymphocytes helps to discriminate active TB from LTBI. CLINICAL IMPLICATIONS: Sequential addition of CD161-T cell expression response to TBAg/PHA ratio increases performance to distinguish ATB from LTBI and aids clinician to thoroughly investigate for ATB in clinically suspected of tuberculosis. DISCLOSURES: No relevant relationships by Putthapoom Lumjiaktase, source=Web Response No relevant relationships by DR MEKAVUTHIKUL, source=Web Response No relevant relationships by Prapaporn Pornsuriyasak, source=Web Response