Reconstitution of Monocyte Subsets and PD-L1 Expression but Not T Cell PD-1 Expression in Obstructive Sleep Apnea Patients upon PAP Therapy

Abstract

Obstructive sleep apnea (OSA) is characterized by nocturnal breathing intermissions resulting in oxidative stress and eventually, a low-grade systemic inflammation. The study aimed to investigate the impact of positive airway pressure (PAP) therapy on the inflammatory milieu as measured by monocyte and T cell phenotypic alterations. Participants were assessed for their OSA severity before PAP therapy and about six months later, including patient-reported outcome and therapy usage by telemetry readout. The distributions of the CD14/CD16-characterized monocyte subsets as well as the CD4/CD8-characterized effector T cell subsets with regard to their PD-1 and PD-L1 expression were analyzed by flow cytometry from blood samples. Data of 25 patients revealed a significant reconstitution of the monocyte subset distribution and a decrease in PD-L1 expression on pan-monocytes and CD8+ T cells without an association to initial AHI and overweight. The PD-1 expression was still increased on T cell subsets, especially on CD4+ TH17/22 cells. We conclude that PAP therapy might have a rapid effect on the monocyte phenotype and overall PD-L1 expression levels. However, T cell immune alterations especially on TH17/22 cells persist longer, indicating an ongoing disturbance of the adaptive immune system.

Dynamics of Circulating CD14/CD16 Monocyte Subsets in Obstructive Sleep Apnea Syndrome Patients upon Hypoglossal Nerve Stimulation

“…We have recently shown, that OSAS patients revealed a significant restoration of monocyte subsets and monocytic PD-L1 expression upon CPAP treatment [ 25 ]. The present study is the first to address OSAS-induced immunological changes in terms of the influence of HNS therapy on a cellular level.…”

“…In healthy individuals, they both account for about 5–10% of peripheral blood monocytes. Increased abundances of pro-inflammatory CD16 + subsets have been associated with different acute and chronic inflammatory diseases [ 25 , 26 ]. The three circulating monocyte subsets all have the ability to acquire macrophage morphology and characteristics, but the exact potential of each subset is still unclear [ 23 ].…”

“…The three circulating monocyte subsets all have the ability to acquire macrophage morphology and characteristics, but the exact potential of each subset is still unclear [ 23 ]. Further investigations revealed a restoration of the CD14/CD16 monocyte subset abundances to normal levels as well as a decrease in monocytic PD-L1 expression in response to continuous positive airway pressure (CPAP) therapy [ 25 ]. However, the dynamics of monocyte subsets in the peripheral blood of OSAS patients upon HNS as a second-line therapy have not been investigated so far.…”

Cellular Immune Dysfunction in Obstructive Sleep Apnea

“…Despite all limitations and difficulties involved in the analysis of immune cells and especially the interpretation of the data, the consideration of this complex topic may provide relevant links to other related topics, such as the oncologic outcome of patients with head and neck cancer ( 54 ), which could be further investigated with markers expressed on immune cells (e.g., PD-1/PD-L1; 21 , 43 , 55 ). Considering that OSA is an inflammatory trigger and risk factor for cardiovascular disease and other comorbidities, we see great perspective opportunities to use immunological activity parameters as a surrogate for the response of OSA patients to therapies or as a starting point for the development of new therapeutic concepts.…”

“…We have found only one study to date investigating the effects of PAP therapy on the human cellular immune system ( 43 ). Although this pilot study has reported very interesting results, it should be critically considered due to the relatively small patient cohort (25 patients) and the non-standard method of OSA-diagnosis in the respective cohort; some participants were tested by polygraphy while others by polysomnography, potentially confounding results.…”