QuantiFERON-TB gold cut-off value: implications for the management of tuberculosis-related ocular inflammation.

PURPOSE: To evaluate the accuracy of QuantiFERON-TB Gold testing in patients with presumptive tuberculosis-ocular inflammation. DESIGN: Prospective nonrandomized case series and clinical laboratory investigation. METHODS: Ninety-six consecutive patients presenting with ocular inflammation between January and October 2007 were tested using QuantiFERON-TB Gold. Positive patients received a 6-month anti-tuberculosis treatment. Patient follow-up ranged from 12 months to 24 months. Treatment was considered effective at the end of follow-up, in cases of no or a 2-point decrease of ocular inflammation (SUN criteria) and systemic corticosteroids stopped or tapered to 10 mg/day. RESULTS: Mean age was 51 ± 17 years. Types of ocular inflammation included scleritis (n = 7), panuveitis (n = 34), and posterior (n = 15), intermediate (n = 14), and anterior uveitis (n = 15). QuantiFERON-TB Gold was positive in 42 cases (44%), negative in 51 cases (53%), and undetermined in 3 cases (3%). Among positive QuantiFERON-TB Gold patients, 25 received a full anti-tuberculosis treatment, which was effective in 15 cases (60%). Associated systemic steroids were given to 6 patients and tapered to 10 mg/day or less in all cases. Median QuantiFERON-TB Gold value was significantly higher in the group with a successful therapeutic response (7.67 IU/mL [0.46 to 33.37]) compared to the group with treatment failure (1.22 IU/mL [0.61 to 4.4]), P = .026. CONCLUSION: Results of anti-tuberculosis treatment were encouraging in QuantiFERON-TB Gold-positive ocular inflammation, especially with values over 2 IU/mL in our study, suggesting that a higher cut-off value than that given by the manufacturer should be considered to better identify ocular inflammation that can benefit from full anti-tuberculosis treatment.

Modulation of interleukin-7 receptor expression characterizes differentiation of CD8 T cells specific for HIV, EBV and CMV.

OBJECTIVES: To further understand differentiation and homeostasis of CD8 T cells specific for HIV, Epstein-Barr Virus (EBV) and cytomegalovirus (CMV) during HIV infection, we investigated interleukin-7 receptor alpha (IL-7Ralpha) expression on those virus-specific T cells. METHODS: Microarrays and cytometry analyses were performed on peripheral blood mononuclear cells (PBMC), total and tetramer-binding virus-specific CD8 T cells from 66 HIV-infected patients. RESULTS: Microarray analysis revealed reduced levels of IL-7Ralpha and increased levels of perforin with disease progression in total PBMC. This loss of IL-7Ralpha expression was observed on CD8 T cells and was inversely related to perforin expression. The relative expression of both molecules defined three new subsets: IL-7Ralpha(pos)Perforin(neg); IL-7Ralpha(loneg)Perforin(lo); and IL-7Ralpha(loneg)Perforin(hi) corresponding to naive and effector-memory CD8 differentiation, as assessed by CD45RA/CD11a. The IL-7Ralpha expression decreased along the CD8 differentiation pathway defined by CD27 and CD28. In contrast, IL-7Ralpha expression was down-modulated on all the CD8 T cells specific for HIV, EBV and CMV that were almost exclusively IL-7Ralpha(lo/neg)Perforin(lo) and was parallel with the CD27 expression. In addition, this low IL-7Ralpha expression on HIV-specific CD8 T cells was independent of virus load and T-cell activation and remained stable during the first 6 months of antiretroviral therapy despite successful control of HIV replication. CONCLUSION: The relative expression of IL-7Ralpha, perforin reveals new aspects of virus-specific CD8 T cell differentiation, independently of T-cell activation and virus load. This opens new perspectives for understanding homeostasis of those cells and immune-based therapeutic strategies.