Plasma LL-37 levels were significantly reduced in individuals with severe OSA compared to healthy controls, with %Stage N1 independently associated with pLL-37 levels, suggesting pLL-37 may serve as a biomarker for sleep quality and the severity of impaired oxygenation during sleep.
Key Findings
Results
Mean plasma LL-37 levels were significantly higher in individuals with AHI < 15 compared to those with AHI ≥ 15.
Mean pLL-37 level was 75.3 ± 29.3 ng/L in the AHI < 15 group versus 47.1 ± 18.3 ng/L in the AHI ≥ 15 group.
Participants were stratified into two groups based on apnea-hypopnea index (AHI): AHI < 15 and AHI ≥ 15.
The study included 58 individuals with OSA and 20 healthy controls.
pLL-37 levels were significantly reduced in individuals with severe OSA compared to healthy controls.
Results
Plasma LL-37 levels showed significant negative correlations with multiple markers of OSA severity.
Significant negative correlations were observed between pLL-37 levels and age, percentage of Stage N1 sleep (%Stage N1), arousal index, AHI, and oxygen desaturation index.
These correlations indicate that as OSA severity increases, plasma LL-37 levels decline.
The arousal index and AHI are both standard polysomnographic measures of sleep disruption and breathing abnormality severity.
Results
Plasma LL-37 levels showed significant positive correlations with markers of better sleep quality and oxygenation.
Significant positive correlations were identified between pLL-37 levels and %Stage N3, percentage of rapid eye movement sleep (%Stage REM), mean percentage of peripheral oxygen saturation (%SpO2 mean), and %SpO2 minimum.
Higher proportions of deep (N3) and REM sleep, as well as better oxygen saturation, were associated with higher pLL-37 levels.
These associations were assessed using polysomnographic (PSG) parameters in the full study cohort.
Results
%Stage N1 sleep was identified as an independent predictor of plasma LL-37 levels in multiple regression analysis.
Multiple regression analysis was conducted to identify independent predictors of pLL-37.
%Stage N1 was the independent factor associated with pLL-37 levels among all variables examined.
The authors suggest this association reflects a decline in pLL-37 with worsening oxygen desaturation.
Stage N1 is the lightest stage of non-REM sleep, and a higher proportion indicates more fragmented, lower-quality sleep.
Background
OSA is characterized by systemic inflammation, intermittent hypoxemia, and immune dysregulation that may increase susceptibility to viral infections.
The study was motivated by associations between OSA and increased susceptibility to viral infections.
LL-37 is an antimicrobial peptide (cathelicidin) with roles in innate immunity.
The study design was a clinical observational study with 58 OSA patients and 20 healthy controls.
Associations between pLL-37 levels, demographic characteristics, and polysomnographic parameters were assessed.
Conclusions
The authors propose that plasma LL-37 may serve as a biomarker for sleep quality and severity of impaired oxygenation during sleep, with implications for immune vulnerability and infection risk in OSA.
The findings suggest pLL-37 may reflect both sleep architecture disruption and nocturnal hypoxemia.
Reduced pLL-37 in more severe OSA implies potential immune vulnerability due to lower levels of this antimicrobial peptide.
The authors note implications for infection risk in OSA patients based on these associations.
This was an observational study, so causal relationships cannot be established.
What This Means
This research suggests that a naturally occurring protein called LL-37, which helps the body fight infections, is present at lower levels in the blood of people with more severe obstructive sleep apnea (OSA). OSA is a sleep disorder where breathing repeatedly stops and starts during sleep, causing drops in blood oxygen levels and poor sleep quality. The study measured LL-37 in the blood of 58 OSA patients and 20 healthy individuals, and found that those with worse apnea — more frequent breathing interruptions and lower oxygen levels — had notably lower LL-37 concentrations. People with an apnea-hypopnea index (AHI) of 15 or more had average LL-37 levels of about 47 ng/L, compared to about 75 ng/L in those with less severe OSA.
The study also found that LL-37 levels were linked to sleep architecture — that is, how much time people spent in different stages of sleep. More time in light, fragmented sleep (Stage N1) was independently associated with lower LL-37 levels, while more time in deep sleep (Stage N3) and REM sleep, along with better blood oxygen levels during the night, were associated with higher LL-37. Statistical analysis identified the proportion of light N1 sleep as the strongest independent predictor of LL-37 levels.
This research suggests that LL-37 could potentially be used as a blood-based marker to reflect both sleep quality and the degree of oxygen disruption in OSA patients. Because LL-37 plays an important role in the immune system's defense against viruses and bacteria, lower levels in people with severe OSA may help explain why these individuals appear to be more vulnerable to infections. Further research would be needed to determine whether treating OSA raises LL-37 levels or reduces infection risk.
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Yamaguchi T, Hosokawa K, Mineta T, Hosokawa R, Odawara S, Chiba R, et al.. (2026). Plasma levels of antimicrobial peptide LL-37 as a biomarker of sleep quality in patients with obstructive sleep apnea: A clinical observational study.. PloS one. https://doi.org/10.1371/journal.pone.0355855