Arthritis & rheumatology (Hoboken, N.J.) · 2026
Multimodal Peripheral Blood Immunophenotyping and Single-Cell Epigenetic Analysis of Knee Osteoarthritis Reveals Expansion and Epigenetic Dysregulation of Treg Cell and Nonclassical Monocyte Populations.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Szymczak Aleksander, Dyson Gabriella, Barrett Montana, Brawner Cindy Miranda, Hanebutt Nicholas, Guthridge Carla, Marlin Caleb, Guthridge Joel, D'souza Padmaja Mehta, Jeffries Matlock A
Аннотация
OBJECTIVE: Osteoarthritis (OA) involves systemic inflammation, yet peripheral blood immunophenotypes and their underlying epigenetic landscapes remain poorly defined. We characterized cellular and chromatin accessibility profiles in knee OA and radiographic progressors (RPs).
METHODS: We performed multimodal immunophenotyping using cytometry by time-of-flight mass spectrometry (CyTOF) on peripheral blood samples from 21 patients with knee OA and 11 healthy controls (HCs). To confirm findings, we developed DNA methylation-based imputation models and applied them to two independent validation cohorts (n = 723). Finally, single-cell Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq) was performed to interrogate chromatin accessibility landscapes in a patient subset.
RESULTS: CyTOF identified significant expansions of CD8+ central memory T cells, CD4+ Treg cells, and nonclassical monocytes in patients with OA versus HCs (all P ≤ 0.05). These expansions were robustly confirmed in the large-scale validation cohorts (all P < 0.0001). Conversely, RPs displayed validated reductions in circulating CD4+ and CD8+ central memory pools. scATAC-seq revealed extensive epigenetic remodeling, particularly within monocytes and Treg cells. Paradoxically, unsupervised clustering indicated that epigenetically defined proinflammatory clusters were depleted in OA blood. Pathway analysis revealed that these depleted clusters possessed activated, migratory phenotypes, whereas the expanded circulating cells among patients with OA displayed quiescent, nonmigratory epigenetic signatures.
CONCLUSION: Knee OA is characterized by validated systemic expansions of specific Treg cell and monocyte subsets. Single-cell epigenetic profiling suggests epigenetically distinct subpopulations driven by age, OA, comorbid conditions, or migration from circulation to the periphery.
METHODS: We performed multimodal immunophenotyping using cytometry by time-of-flight mass spectrometry (CyTOF) on peripheral blood samples from 21 patients with knee OA and 11 healthy controls (HCs). To confirm findings, we developed DNA methylation-based imputation models and applied them to two independent validation cohorts (n = 723). Finally, single-cell Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq) was performed to interrogate chromatin accessibility landscapes in a patient subset.
RESULTS: CyTOF identified significant expansions of CD8+ central memory T cells, CD4+ Treg cells, and nonclassical monocytes in patients with OA versus HCs (all P ≤ 0.05). These expansions were robustly confirmed in the large-scale validation cohorts (all P < 0.0001). Conversely, RPs displayed validated reductions in circulating CD4+ and CD8+ central memory pools. scATAC-seq revealed extensive epigenetic remodeling, particularly within monocytes and Treg cells. Paradoxically, unsupervised clustering indicated that epigenetically defined proinflammatory clusters were depleted in OA blood. Pathway analysis revealed that these depleted clusters possessed activated, migratory phenotypes, whereas the expanded circulating cells among patients with OA displayed quiescent, nonmigratory epigenetic signatures.
CONCLUSION: Knee OA is characterized by validated systemic expansions of specific Treg cell and monocyte subsets. Single-cell epigenetic profiling suggests epigenetically distinct subpopulations driven by age, OA, comorbid conditions, or migration from circulation to the periphery.