LL-37 concentrations and the relationship to vitamin D, immune status, and inflammation in HIV-infected children and young adults

Abstract

Antimicrobial peptide LL-37 is produced in response to active vitamin D to exert immunomodulatory effects and inhibits HIV replication in vitro. To date, no studies have investigated LL-37 in HIV-infected patients. This study sought to investigate LL-37 and the relationship to 25-hydroxyvitamin D [25(OH)D] and HIV-related variables in this population. HIV-infected subjects and healthy controls ages 1-25 years old were prospectively enrolled in this cross-sectional study. Fasting plasma LL-37 and 25(OH)D concentrations were measured in duplicate with ELISA. HIV(+) subjects (36 antiretroviral therapy (ART)-experienced subjects; 27 ART-naïve subjects) and 31 healthy controls were enrolled. Overall, 93% were black and the median age was 20 years. There was no difference in median (interquartile range) LL-37 between the HIV-infected group and controls [58.3 (46.4,69.5) vs. 51.3 (40.8,98.2) ng/ml, respectively; p=0.57]; however, the ART-experienced group had higher concentrations than the ART-naive group [66.2 (55.4,77.0) vs. 48.9 (38.9,57.9) ng/ml, respectively; p<0.001]. LL-37 was positively correlated with 25(OH)D in controls, but not in HIV-infected groups, and was positively correlated with current CD4 and ΔCD4 (current-nadir) in the ART-experienced group. After adjustment for age, race, sex, and HIV duration, the association between LL-37 and CD4 remained significant. These findings suggest that HIV and/or HIV-related variables may alter the expected positive relationship between vitamin D and LL-37 and should be further investigated.

FIG. 1.

Box and whisker plots for LL-37 concentrations by antiretroviral treatment (ART) status. Box and whisker plots show the LL-37 concentrations for HIV-infected, ART-experienced subjects (A), HIV-infected, ART-naive subjects (B), and healthy controls (C). Each HIV group was compared to each other and to the healthy controls. The ART-experienced group had statistically higher LL-37 concentrations compared to the ART-naive group [median (IQR) ART-exp.: 66.2 (55.4, 77.0) ng/ml; ART-naive: 48.9 (38.9, 57.9) ng/ml; p<0.001]. There was no difference between the ART-experienced group and the healthy controls [median IQR controls: 51.3 (40.8, 98.2) ng/ml; p=0.68]. ART, antiretroviral therapy; Exp., experienced; IQR, interquartile range.