RESUMO
PURPOSE: Highly active systemic lupus erythematosus (SLE) causes a high risk of tuberculosis (TB) infection in SLE patients in Indonesia, a country in which the disease, especially extrapulmonary TB, is endemic. Interferon (IFN)-γ releasing assay (IGRA) can detect latent or previous TB infection. This study sought to determine latent TB infection and levels of IFN-γ, a key player in various inflammation and autoimmune disease, in patients with SLE and relate findings to disease activity. PATIENTS AND METHODS: This experimental study included 79 female subjects distributed into three groups of active SLE, quiescent SLE and healthy controls. We used SLE Disease Activity Index-2000 (SLEDAI-2K) scores to stratify the subjects. Each group underwent IGRA testing using the QuantiFERON-TB Gold Plus kit. RESULTS: We recruited 59 female patients with SLE. The patients had a median age and disease duration 30 and 5 years, respectively. Statistical analysis using the Kruskal-Wallis test showed that active condition, high SLEDAI-2K score and immunosuppressive therapies affect IGRA results. Specifically, healthy controls (n=20) were most likely to have negative IGRA results (67.09%), whilst 27.27% of active cases (n=33) and 3.85% of quiescent cases (n=26) had indeterminate results (p=0.02). The number of immunosuppressant therapies was significantly negatively correlated with IFN-γ (p=0.004). No difference in IFN-γ concentration was detected amongst the active and other groups (p>0.05). CONCLUSION: High-activity SLE and immunosuppressive therapies cause dysregulation of the immune response, which, in turn, influences IGRA results. Thus, additional testing is necessary to detect TB infection in patients with SLE.
RESUMO
Immunopathology contributes to high mortality in tuberculous meningitis (TBM) but little is known about the blood and cerebrospinal fluid (CSF) immune response. We prospectively characterised the immune response of 160 TBM suspects in an Indonesian cohort, including 67 HIV-negative probable or definite TBM cases. TBM patients presented with severe disease and 38% died in 6 months. Blood from TBM patients analysed by flow cytometry showed lower αßT and γδT cells, NK cells and MAIT cells compared to 26 pulmonary tuberculosis patients (2.4-4-fold, all p < 0.05) and 27 healthy controls (2.7-7.6-fold, p < 0.001), but higher neutrophils and classical monocytes (2.3-3.0-fold, p < 0.001). CSF leukocyte activation was higher than in blood (1.8-9-fold). CSF of TBM patients showed a predominance of αßT and NK cells, associated with better survival. Cytokine production after ex-vivo stimulation of whole blood showed a much broader range in TBM compared to both control groups (p < 0.001). Among TBM patients, high ex-vivo production of TNF-α, IL-6 and IL-10 correlated with fever, lymphocyte count and monocyte HLA-DR expression (all p < 0.05). TBM patients show a strong myeloid blood response, with a broad variation in immune function. This may influence the response to adjuvant treatment and should be considered in future trials of host-directed therapy.
