Use of T Cell-Based Diagnosis of Tuberculosis Infection to Optimize Interpretation of Tuberculin Skin Testing for Child Tuberculosis Contacts

BACKGROUND: Treatment of recent tuberculosis infection in children <2 years old is essential because of high risk of progression to disease, but diagnosis is hindered by the inaccuracy of the tuberculin skin test (TST). More accurate T cell-based tests for infection could enhance diagnosis by optimizing TST interpretation. METHODS: 979 child tuberculosis contacts in Istanbul underwent TST and enzyme-linked immunospot (ELISpot) testing. Using ELISpot results as a reference standard, we assessed the effect of age and BCG-vaccination on sensitivity and specificity of TST, and computed optimal TST cut-off points (OCPs) using receiver operator characteristic curves. RESULTS: Using a ≥10mm TST cut-off point, sensitivity of TST was 66% in children <2y, lower than in older children (p=0.006). Specificity was 75% in BCG-vaccinated children, compared with 92% in unvaccinated children (p=0.001). OCPs improved TST specificity in children with 1 BCG scar with little loss of sensitivity. Despite use of OCPs, sensitivity of TST remained <70% in children <2y, specificity remained <87% in BCG-vaccinated children >2y and overall accuracy was low in children with >1 BCG scar. CONCLUSIONS: Negative TST results cannot exclude tuberculosis infection in child tuberculosis contacts <2 years old, supporting use of preventive therapy regardless of TST results in this age group. In children >2 years old, accuracy of TST can be improved by adjustment of cut-off points in BCG-vaccinated children but remains poor in children with >1 BCG scar. This methodology can define optimal TST cut-off points for diagnosis of tuberculosis infection tailored to target populations

Oligoclonal T cell expansions in patients with Behçet's disease

Behçet's disease (BD) is a multisystem disorder with oral and genital ulcers, mucocutaneous, ocular, joint, vascular and central nervous system involvement. In this study, the peripheral T cell repertoire was analysed in patients with BD with MoAbs against T cell receptor (TCR) Vβ gene products in CD4+ and CD8+ T cell compartments, and these were compared with rheumatoid arthritis (RA) patients and healthy controls (HC). In the CD4+ T cell compartment, oligoclonal TCR Vβ expression was observed in 56% of BD (10/18), 71% of RA (5/7) patients and 21% (3/14) of HC. In the CD8+ T cell group 50% of BD (9/18), 57% of RA patients and 28% of HC (4/14) had an oligoclonal TCR repertoire. An increase of TCR Vβ5.1 subset was observed in five BD patients among CD8+ T cells. Other elevations of TCR Vβ subsets were heterogeneously distributed with one to three different Vβ subsets. Our results suggest an antigen-driven oligoclonal increase of T cells in BD. There was no overall increase in any Vβ group to suggest a superantigen effect. Analysis of the responsible antigens causing the increase in T cell subsets may give insights into the aetiopathogenesis of BD and immunomodulation of these T cells may lead to new treatments