# Unlocking the Diagnostic Challenge of Tuberculosis and Sarcoidosis Intrathoracic Lymphadenopathy: Potential Role of HMGB1 and miRNA-221 as Diagnostic Tools

## TL;DR

This study investigates biomarkers like HMGB1 and miRNA-221 to help distinguish between tuberculosis and sarcoidosis-related lymph node issues.

## Contribution

The study identifies miRNA-221 as a potential novel biomarker for differentiating tuberculosis from sarcoidosis.

## Key findings

- miRNA-221 expression was significantly higher in tuberculosis patients compared to sarcoidosis and controls.
- HMGB1 levels were elevated in both tuberculosis and sarcoidosis patients compared to healthy controls.
- miRNA-221 showed potential in differentiating tuberculosis from sarcoidosis, though further validation is needed.

## Abstract

Tuberculosis and sarcoidosis can present with similar clinical and radiological features, especially intrathoracic lymphadenopathy, complicating differential diagnosis. This study explored the potential utility of QuantiFERON-TB Gold (QFT), serum High Mobility Group Box 1 protein (HMGB1), and microRNA-221 (miRNA-221) relative expression as biomarkers to aid in distinguishing tuberculosis-related intrathoracic lymphadenopathy (TBIL) from sarcoidosis-related intrathoracic lymphadenopathy (SAIL). The study included 27 patients with TBIL, 27 patients with SAIL, and 27 healthy controls. QFT results, serum HMGB1 levels, and miRNA-221 relative expression were measured and compared across groups using univariable and exploratory multivariable analyses. Significant differences were observed among the study groups for serum HMGB1 levels, miRNA-221 expression, and QFT results (p < 0.001). Both TBIL and SAIL patients had significantly higher HMGB1 levels compared with healthy controls, consistent with inflammatory activity. In contrast, miRNA-221 expression was significantly elevated in TBIL patients compared with both SAIL patients and controls. Exploratory analyses suggested a potential contribution of miRNA-221 to differentiating TBIL from SAIL, whereas the effects of HMGB1 and QFT were less pronounced after adjustment. The findings suggest that miRNA-221, alongside HMGB1 and QFT, may contribute to the differentiation of TBIL from SAIL, although validation in larger cohorts is necessary.