RT Journal Article
SR Electronic
T1 BCG-specific IgG-secreting peripheral plasmablasts as a potential biomarker of active tuberculosis in HIV negative and HIV positive patients
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 269
OP 276
DO 10.1136/thoraxjnl-2012-201817
VO 68
IS 3
A1 Senait Ashenafi
A1 Getachew Aderaye
A1 Martha Zewdie
A1 Rubhana Raqib
A1 Amsalu Bekele
A1 Isabelle Magalhaes
A1 Beede Lema
A1 Meseret Habtamu
A1 Rokeya Sultana Rekha
A1 Getachew Aseffa
A1 Markus Maeurer
A1 Abraham Aseffa
A1 Mattias Svensson
A1 Jan Andersson
A1 Susanna Brighenti
YR 2013
UL http://thorax.bmj.com/content/68/3/269.abstract
AB Background Diagnosis of active tuberculosis (TB) among sputum-negative cases, patients with HIV infection and extra-pulmonary TB is difficult. In this study, assessment of BCG-specific IgG-secreting peripheral plasmablasts, was used to identify active TB in these high-risk groups. Methods Peripheral blood mononuclear cells were isolated from patients with TB and controls and cultured in vitro using an assay called Antibodies in Lymphocyte Supernatant, which measures spontaneous IgG antibody release from migratory plasmablasts. A BCG-specific ELISA and flow cytometry were used to quantify in vivo activated plasmablasts in blood samples from Ethiopian subjects who were HIV negative or HIV positive. Patients diagnosed with different clinical forms of sputum-negative active TB or other diseases (n=96) were compared with asymptomatic individuals including latent TB and non-TB controls (n=85). Immunodiagnosis of TB also included the tuberculin skin test and the interferon (IFN)-γ release assay, QuantiFERON. Results This study demonstrated that circulating IgG+ plasmablasts and spontaneous secretion of BCG-specific IgG antibodies were significantly higher in patients with active TB compared with latent TB cases and non-TB controls. BCG-specific IgG titres were particularly high among patients coinfected with TB and HIV with CD4 T-cell counts <200 cells/ml who produced low levels of Mycobacterium tuberculosis-specific IFNγ in vitro. Conclusions These results suggest that BCG-specific IgG-secreting peripheral plasmablasts could be successfully used as a host-specific biomarker to improve diagnosis of active TB, particularly in people who are HIV positive, and facilitate administration of effective treatment to patients. Elevated IgG responses were associated with impaired peripheral T-cell responses, including reduced T-cell numbers and low M tuberculosis-specific IFNγ production.