Immunological Evidence for the Role of Mycobacteria in Sarcoidosis: A Meta-Analysis

<div><p>Background</p><p>Sarcoidosis is a granulomatous disease, the etiology of which is currently unknown. The role of mycobacteria in the etiology of sarcoidosis has been extensively investigated. In this meta-analysis, we assessed the immunological evidence of the possible role of mycobacteria in the pathogenesis and development of sarcoidosis.</p><p>Methods</p><p>We performed a systematic search of relevant articles from PubMed, Embase and Cochrane Library databases published between January 1990 and October 2015. Data extracted from the articles were analyzed with Review Manager 5.3 (Cochrane Collaboration, Oxford, UK).</p><p>Results</p><p>In this meta-analysis, 13 case-control studies (733 participants) were considered eligible according to our criteria. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). The positivity incidence of the immune response (either the cell-mediated response or humoral response) in sarcoidosis patients was significantly higher than that in controls, as determined using fixed-effects model. The odds ratio (OR) of the positivity incidence of T-cell response in the patients with sarcoidosis versus the controls with PPD- or unknown PPD status was 5.54 (95% CI 3.56–8.61); the ORs were 16.70 (95% CI 8.19–34.08) and 1.48 (95% CI 0.74–2.96) for the two subgroups with PPD- controls and unknown PPD status respectively. However, the OR of the positivity incidence in patients with sarcoidosis versus PPD+ controls (latent tuberculosis infection; LTBI) was 0.26 (95% 0.10–0.66). Regarding the humoral response, pooled analysis of the positivity incidence revealed an OR (95%CI) of 20.43 (5.53–75.53) for the patients with sarcoidosis versus controls; the ORs were 11.93 (95% CI 2.15–66.27) and 41.97 (95% CI 5.24–336.15) in two subgroups of controls with PPD- and unknown PPD statuses respectively. Data on heterogeneity and evidence of publication bias were examined.</p><p>Conclusions</p><p>This meta-analysis confirmed the existence of an association between mycobacteria (especially <i>M</i>.<i>tuberculosis</i>) and sarcoidosis. The current available evidence indicates that some insoluble mycobacterial antigens that preferentially within the body are involved in the pathogenesis of sarcoidosis rather than the whole mycobacteria and that they elicit a type IV immune response.</p></div

Forest plot of trials analyzing the positivity incidence of T-cell response to <i>M</i>. <i>tuberculosis</i> antigens in sarcoidosis patients versus PPD+ controls (LTBI).

<p>LTBI = latent tuberculosis infection.</p

Flow diagram of assessment of studies identified in meta-analysis.

<p>Flow diagram of assessment of studies identified in meta-analysis.</p

Forest plot of trials analyzing the positivity incidence of the humoral response to <i>M</i>. <i>tuberculosis</i> antigens in sarcoidosis patients versus controls.

<p>Forest plot of trials analyzing the positivity incidence of the humoral response to <i>M</i>. <i>tuberculosis</i> antigens in sarcoidosis patients versus controls.</p

Funnel plot assessing publication bias.

<p><b>a. Funnel plot for the studies on the T-cell response to <i>M</i>. <i>tuberculosis</i> antigens with controls of PPD- or unknown PPD status; b. Funnel plot for the studies on the T-cell response to <i>M</i>. <i>tuberculosis</i> antigens with PPD+ controls; c. Funnel plot for studies on the humoral response to <i>M</i>. <i>tuberculosis</i> antigens</b>. SA = sarcoidosis.</p

The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies.

<p>The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies.</p