Diagnostic predictors of active tuberculosis infection in diabetic patients with latent tuberculosis: A review on cathelicidin and 1,25-dihydroxyvitamin D3

Abstract

Background: Diabetes Mellitus has been identified as one of factors causing increased risks of latent TB infection. The roles of cathelicidin LL-37, 1.25(OH)2D3 as well as their correlation with specific IFN-γ in latent TB has not been extensively identified. Aims and Objectives: Our study was aimed to identify proportion of latent TB infection in patients with DM and to identify the role of cathelicidin, 1.25(OH)2D3, vitamin D and other clinical factors as predictors for active TB infection in diabetic patients with latent TB. Methods: Our study was conducted in 2 stages. The first-stage study was a cross-sectional study to identify the proportion of latent TB infection in patients with DM without any history of TB, which was continued with a case-control study to identify the roles of predictive biomarkers (cathelicidin LL-37, 25(OH)D3, 1.25(OH)2D3 and IFN-γ) as well as clinical predictive factors for active TB infection in diabetic patients with latent TB. Results: Out of 242 diabetic patients without any history of TB who underwent screening test for latent TB, there were 78 (33.2%) subjects with a diagnosis of latent TB and 1 subject was diagnosed with active TB. There was significant association on the level of cathelicidin LL-37 in DM patient with latent TB, active TB and without TB infection (23.49 ng/mL vs. 49.6 ng/mL vs. 10.46 ng/mL, P < 0,005). Almost all of subjects with DM showed low levels of vitamin D, most in subject with active TB (97%). There was no significant association between 1.25(OH)2D3 and 25(OH)D3 in DM patients with latent TB, active TB and without TB infection. There was a significant association on the levels of IFN-γ ((TB1 1.4 IU/mL vs. 0.03 IU/mL P < 0.005; TB2 1.4 IU/mL vs. 0.04 IU/mL P < 0.005) in DM subjects with latent TB and those without TB infection; however, no significant association was found in DM subjects with latent TB and active TB. History of smoking, HbA1C > 9.5% and cathelicidin LL-37 levels of > 30 ng/mL were predictors for latent TB into active TB in DM patients. Conclusion: Cathelicidin LL-37 can serve as a biomarker of latent TB progressiveness in patients with DM.