Dataset Information

Autoantibody prevalence in active tuberculosis: reactive or pathognomonic?

ABSTRACT:

Objectives

To evaluate the autoantibody in patients without corresponding symptoms, whether these autoantibody are pathognomonic or not. We hypothesised that autoantibody may be reactive to chronic infection, such as tuberculosis (TB).

Design

Randomised, case-control cohort study.

Setting

A tertiary centre in Taiwan.

Participants

We randomly chose 100 patients out of the data bank of patients with TB in a tertiary medical centre. All patients completed the sera sampling. We chose 100 patients according to autoantibody prevalence in previous literature. We also chose 100 medical staff as control group.

Interventions

We tested anti-SSA, anti-SSB, anti-Sm, anti ribonucleoprotein, anti-Scl 70, anticentromere, anti-double-stranded DNA, anticardiolipin IgG and IgM in all patient and control groups. The clinical symptoms and the underlying disease were all recorded.

Primary and secondary outcome measures

The result of sera antibody titre was recorded. For those with specific positive serology results, following examination was carried out after a 3-month anti-TB medication.

Results

Anticardiolipin IgG titre was significantly higher in patients with TB than in control group. We compared the result with previous population study and found that anti-Scl70 is also significantly higher in patients with TB. The following up data in anti-Scl70 revealed decreased titre after treatment. No correlation between sera titre and clinical conditions was observed.

Conclusions

In TB endemic areas, a significant proportion (32%) of patients with TB have elevated autoantibody titres, especially anticardiolipin IgG and anti-Scl-70. Mycobacterial studies should be performed in patients with elevated serum autoantibody titres but without the typical or multiple manifestations of autoimmune diseases.

Trial registration

The study was approved by the Institutional Review Board of the hospital (NTUH REC: 9561707008) after informed consent had been obtained from the patients.

SUBMITTER: Shen CY

PROVIDER: S-EPMC3731725 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Autoantibody prevalence in active tuberculosis: reactive or pathognomonic?

Shen Chieh-Yu CY Hsieh Song-Chou SC Yu Chia-Li CL Wang Jann-Yuan JY Lee Li-Na LN Yu Chong-Jen CJ

BMJ open 20130726 7

<h4>Objectives</h4>To evaluate the autoantibody in patients without corresponding symptoms, whether these autoantibody are pathognomonic or not. We hypothesised that autoantibody may be reactive to chronic infection, such as tuberculosis (TB).<h4>Design</h4>Randomised, case-control cohort study.<h4>Setting</h4>A tertiary centre in Taiwan.<h4>Participants</h4>We randomly chose 100 patients out of the data bank of patients with TB in a tertiary medical centre. All patients completed the sera sampl ...[more]

PMID: 23892369

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Project description:BACKGROUND: Tuberculin-specific T-cell responses have low diagnostic specificity in BCG vaccinated populations. While subunit-antigen (e.g. ESAT-6, CFP-10) based tests are useful for diagnosing latent tuberculosis infection, there is no reliable immunological test for active pulmonary tuberculosis. Notably, all existing immunological tuberculosis-tests are based on T-cell response size, whereas the diagnostic potential of T-cell response quality has never been explored. This includes surface marker expression and functionality of mycobacterial antigen specific T-cells. METHODOLOGY/PRINCIPAL FINDINGS: Flow-cytometry was used to examine over-night antigen-stimulated T-cells from tuberculosis patients and controls. Tuberculin and/or the relatively M. tuberculosis specific ESAT-6 protein were used as stimulants. A set of classic surface markers of T-cell naïve/memory differentiation was selected and IFN-gamma production was used to identify T-cells recognizing these antigens. The percentage of tuberculin-specific T-helper-cells lacking the surface receptor CD27, a state associated with advanced differentiation, varied considerably between individuals (from less than 5% to more than 95%). Healthy BCG vaccinated individuals had significantly fewer CD27-negative tuberculin-reactive CD4 T-cells than patients with smear and/or culture positive pulmonary tuberculosis, discriminating these groups with high sensitivity and specificity, whereas individuals with latent tuberculosis infection exhibited levels in between. CONCLUSIONS/SIGNIFICANCE: Smear and/or culture positive pulmonary tuberculosis can be diagnosed by a rapid and reliable immunological test based on the distribution of CD27 expression on peripheral blood tuberculin specific T-cells. This test works very well even in a BCG vaccinated population. It is simple and will be of great utility in situations where sputum specimens are difficult to obtain or sputum-smear is negative. It will also help avoid unnecessary hospitalization and patient isolation.

Project description:Macrophage dysfunction is associated with increased tuberculosis (TB) susceptibility in patients with human immunodeficiency virus (HIV) infection. However, the mechanisms underlying how HIV infection impairs macrophage function are unclear. Here, we found that levels of autoantibodies against red blood cells (RBCs) were significantly elevated in patients with HIV as determined by direct antiglobulin test (DAT). DAT positivity was significantly associated with TB incidence in both univariate and multivariate analyses (odds ratio [OR]?=?11.96 [confidence interval {CI}, 4.68 to 30.93] and 12.65 [3.33 to 52.75], respectively). Ex vivo analysis showed that autoantibodies against RBCs enhanced erythrophagocytosis and thus significantly impaired macrophage bactericidal function against intracellular Mycobacterium tuberculosis Mechanistically, autoantibody-mediated erythrophagocytosis increased heme oxygenase-1 (HO-1) expression, which inhibited M. tuberculosis-induced autophagy in macrophages. Silencing ATG5, a key component for autophagy, completely abrogated the effect of erythrophagocytosis on macrophage bactericidal activity against M. tuberculosis In conclusion, we have demonstrated that HIV infection increases autoantibody-mediated erythrophagocytosis. This process impairs macrophage bactericidal activity against M. tuberculosis by inhibiting HO-1-associated autophagy. These findings reveal a novel mechanism as to how HIV infection increases TB susceptibility.IMPORTANCE HIV infection significantly increases TB susceptibility due to CD4 T-cell loss and macrophage dysfunction. Although it is relatively clear that CD4 T-cell loss represents a direct effect of HIV infection, the mechanism underlying how HIV infection dampens macrophage function is unknown. Here, we show that HIV infection enhances autoantibody-mediated erythrophagocytosis, which dampens macrophage bactericidal activity against TB by inhibiting HO-1-associated autophagy. Our findings reveal a novel mechanism explaining how HIV infection increases susceptibility to TB. We propose that DAT could be a potential measure to identify HIV patients who are at high TB risk and who would be suitable for anti-TB chemotherapy preventive treatment.

Dataset Information

Autoantibody prevalence in active tuberculosis: reactive or pathognomonic?

Objectives

Design

Setting

Participants

Interventions

Primary and secondary outcome measures

Results

Conclusions

Trial registration

Publications

Autoantibody prevalence in active tuberculosis: reactive or pathognomonic?

Similar Datasets

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