Vitamin D3 Status and the Association with Human Cathelicidin Expression in Patients with Different Clinical Forms of Active Tuberculosis

Low vitamin D (vitD(3)) is one of the most common nutritional deficiencies in the world known to be associated with numerous medical conditions including infections such as tuberculosis (TB). In this study, vitD(3) status and its association with the antimicrobial peptide, human cathelicidin (LL-37), was investigated in Ethiopian patients with different clinical forms of TB. Patients with active TB (n = 77) and non-TB controls (n = 78) were enrolled in Ethiopia, while another group of non-TB controls (n = 62) was from Sweden. Active TB included pulmonary TB (n = 32), pleural TB (n = 20), and lymph node TB (n = 25). Concentrations of 25-hydroxyvitamin D-3 (25(OH)D-3) were assessed in plasma, while LL-37 mRNA was measured in peripheral blood and in samples obtained from the site of infection. Median 25(OH)D-3 plasma levels in active TB patients were similar to Ethiopian non-TB controls (38.5 versus 35.0 nmol/L) and vitD(3) deficiency (<50 nmol/L) was common in both groups (73%). Ethiopians (low latitude) had significantly lower 25(OH)D-3 levels compared with Swedish non-TB controls (51.0 nmol/L, high latitude), but vitD(3) status was not affected by tuberculin-positivity or HIV infection. Patients with local lymph node TB had significantly higher 25(OH)D-3 levels compared with pulmonary TB patients (48.0 versus 29.0 nmol/L). Moreover, plasma 25(OH)D-3 levels correlated with local LL-37 expression in granulomatous lesions in TB infected lymph nodes. Instead, systemic LL-37 mRNA expression in blood cells was elevated compared with the site of infection in pulmonary and pleural TB. Low vitD(3) status may be associated with an enhanced peripheral expression of LL-37 in patients with intrathoracic TB that could result from chronic inflammation.