Impact of vitamin D status and cathelicidin antimicrobial peptide on adults with active pulmonary TB globally: A systematic review and meta-analysis

Abstract

Background Tuberculosis remains a global threat and a public health problem that has eluded attempts to eradicate it. Low vitamin D levels have been identified as a risk factor for tuberculosis infection and disease. The human cathelicidin LL-37 has both antimicrobial and immunomodulatory properties and is dependent on vitamin D status. This systematic review attempts to compare vitamin D andLL-37 levels among adult pulmonary tuberculosis patients to non-pulmonary TB individuals between 16–75 years globally and to determine the association between vitamin D and cathelicidin and any contributing factor among the two study groups. Methods/Design We performed a search, through PubMed, HINARI, Google Scholar, EBSCOhost, and databases. A narrative synthesis through evaluation of vitamin D and LL-37 levels, the association of vitamin D and LL-37, and other variables in individual primary studies were performed. A random-effect model was performed and weighted means were pooled at a 95% confidence interval. This protocol is registered under the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42019127232. Results Of the 2507 articles selected12 studies were eligible for the systematic review and of these only nine were included in the meta-analysis for vitamin D levels and six for LL-37 levels. Eight studies were performed in Asia, three in Europe, and only one study in Africa. The mean age of the participants was 37.3±9.9 yrs. We found low vitamin D and high cathelicidin levels among the tuberculosis patients compared to non-tuberculosis individuals to non-tuberculosis. A significant difference was observed in both vitamin D and LL-37 levels among tuberculosis patients and non-tuberculosis individuals (p = < 0.001). Conclusion This study demonstrated that active pulmonary tuberculosis disease is associated with hypovitaminosis D and elevated circulatory cathelicidin levels with low local LL-37 expression. This confirms that vitamin D status has a protective role against tuberculosis disease.

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

“…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 ]. Recent studies in vitamin D–supplemented volunteers failed to enhance cathelicidin plasmatic level [ 13 , 14 ]; our team observed the same absence of effect in a placebo-controlled clinical trial with vitamin D supplementation in elderly volunteers [ 15 ].…”

Potential Role of Vitamins A, B, C, D and E in TB Treatment and Prevention: A Narrative Review

“…However, it is unclear whether VD deficiency is a possible cause or consequence of the disease. Numerous in vitro studies have demonstrated the role and potential benefit of VD in TB, showing that VD suppresses the replication of MTB in vitro [ 82 , 83 ]; few clinical trials have been performed to evaluate the efficacy of VD supplementation in preventing the development of the disease, failing to show a reduction in the risk of infection and development of disease [ 84 , 85 ].…”

“…In vivo but few and with numerically small samples and data inaccuracies [52,53,73,84,85] -VD and TB prevention: conflicting results that do not show a clear correlation in vivo between VD supplementation and prevention of disease development -VD and treatment of TB: infusion of high doses of VD did not reach an early microscopic negativization, compared to placebo, but in a metanalysis of RCT it seems that VD can accelerate sputum culture conversion in patients with multidrug-resistant pulmonary TB. -In patients receiving 4-drug therapy, despite VD supplementation, there is no significant increase in serum VD levels.…”

Hypovitaminosis D among newly diagnosed pulmonary TB patients and their household contacts in Uganda

“…A study from Tanzania noted inconsistencies due to the selection bias of the control group 32 . On the other hand, according to our previous systematic review and meta-analysis, these inconsistencies are attributed to the variable definition of vitamin D deficiency 33 . Notably, the present study used the definition of the Endocrine Society for clear categorization of deficient and insufficient groups.…”