A comparison of vitamin D and cathelicidin (LL-37) levels between patients with active TB and their healthy contacts in a high HIV prevalence setting: a prospective descriptive study

Abstract

Background Studies from Asia and Europe indicate an association between vitamin D deficiency and susceptibility to TB. We performed an observational case-control study to determine vitamin D and cathelicidin (LL-37) levels and their association with active TB in newly diagnosed and microbiologically confirmed adult TB patients in Zambia, a high HIV prevalence setting. Methods Both total vitamin D and LL-37 were measured using ELISA from serum and supernatant isolated from cultured whole blood that was stimulated with heat-killed Mycobacterium tuberculosis. Statistical analysis was performed using STATA statistical software version 12. Results The median vitamin D in TB patients and healthy contacts was 28.7 (19.88–38.64) and 40.8 (31.2–49.44) ng/ml, respectively (p<0.001). The median LL-37 in TB patients compared with healthy contacts was 1.87 (2.74–8.93) and 6.73 (5.6–9.58) ng/ml, respectively (p=0.0149). Vitamin D correlation with LL-37 in healthy contacts was R2=0.7 (95% CI 0.566 to 0.944), p<0.0001. Normal vitamin D significantly predicted a healthy status (OR 4.06, p=0.002). Conclusions Significantly lower levels of vitamin D and LL-37 are seen in adults with newly diagnosed active TB. Longitudinal studies across various geographical regions are required to accurately define the roles of vitamin D and LL-37 in preventive and TB treatment outcomes.

25-Hydroxyvitamin D potentializes extracellular cathelicidin release from human PBMC stimulated ex vivo with either bacterial (LPS) or viral (P: IC) mimetics

“…In healthy volunteers, Bhan et al (2011) [ 9 ] and Dixon et al (2012) [ 10 ] also reported a significant positive correlation but only when serum concentration of 25(OH)D was under the threshold value of 32 ng/ml. In contrast, Stukes et al (2016) and Lungu et al (2021) were unable to confirm the correlation between 25(OH)D and LL-37 circulating levels in a cohort of healthy volunteers [ 7 , 11 ]. The meta-analysis performed by Acen et al (2021) does not have sufficient eligible studies to perform a correlation meta-analysis of vitamin D and LL-37 levels [ 12 ].…”

“…While a positive correlation between 25(OH)D supplementation and CAMP expression has been established [ 5 ], the link between circulating 25(OH)D and the hCAP18 and/or LL-37 blood peptides remains unclear both in healthy and diseased subjects. In volunteers presenting health issues, Kanda et al (2012) have reported a positive correlation in atopic dermatitis patients as well as Lungu et al (2021) in tuberculosis patients [ 6 , 7 ] contrary to Meca et al (2021) [ 8 ]. In healthy volunteers, Bhan et al (2011) [ 9 ] and Dixon et al (2012) [ 10 ] also reported a significant positive correlation but only when serum concentration of 25(OH)D was under the threshold value of 32 ng/ml.…”