Oliveira Thaliane Carvalho, Braun André Cardoso, Dutra Rachel Pinto Dornelles, Marchesan Moreira Breit Mariana, Abib Julia Brum, Thomazini Ludmilla C D, Argenti Gustavo, Alves Correa Maria Paula, Almeida Giovanna, Vidart Josi, Wajner Simone Magagnin
Endocr Connect. 2025 Mar 14;14(4). doi: 10.1530/EC-24-0677. Print 2025 Apr 1.
Altered type 2 and 3 deiodinase (D2 and D3) can disrupt thyroid hormone metabolism and contribute to non-thyroidal illness syndrome (NTIS). The impact of the colocalization of D2 and D3, and their expression in immune cells isolated from critically ill patients, are still not fully understood. Our objective was to assess the D2 and D3 in the neutrophils and monocytes of patients admitted to the intensive care unit (ICU) for any cause. Blood samples were collected from 96 ICU patients at admission and on day 7. We employed different cell gradients and flow cytometry to separate and purify cells from whole blood. Parameters indicating redox balance were measured, including total carbonyls, sulfhydryl content and glutathione (GSH) levels. The expression and colocalization of DIO2 and DIO3 were evaluated through RNAscope, real-time PCR (polymerase chain reaction) and immunofluorescence. The formation of carbonyls, a marker for oxidative damage to proteins, was elevated in all patients, while sulfhydryl and GSH levels were found to be reduced. The expression of DIO2 and DIO3 in neutrophils and monocytes from both surviving and deceased patients demonstrated significant variations in localization. Notably, elevated levels of D3 protein showed distinct distribution patterns between the groups. Levels of T3 in each cell type varied and were correlated with patient outcomes. The specific distribution of these enzymes has also been associated with prognosis. The set of these findings enhances our understanding of the pathophysiology of NTIS and may provide valuable information for prognostic assessments.
2型和3型脱碘酶（D2和D3）的改变会破坏甲状腺激素代谢，并导致非甲状腺疾病综合征（NTIS）。D2和D3的共定位及其在重症患者分离出的免疫细胞中的表达情况，目前仍未完全明确。我们的目的是评估因任何原因入住重症监护病房（ICU）的患者中性粒细胞和单核细胞中的D2和D3。在入院时及入院第7天采集了96例ICU患者的血样。我们采用不同的细胞梯度和流式细胞术从全血中分离和纯化细胞。测量了指示氧化还原平衡的参数，包括总羰基、巯基含量和谷胱甘肽（GSH）水平。通过RNAscope、实时聚合酶链反应（PCR）和免疫荧光评估DIO2和DIO3的表达及共定位情况。所有患者中蛋白质氧化损伤标志物羰基的形成均升高，而巯基和GSH水平降低。存活患者和死亡患者中性粒细胞和单核细胞中DIO2和DIO3的表达在定位上表现出显著差异。值得注意的是，D3蛋白水平升高在两组间呈现出不同的分布模式。每种细胞类型中T3的水平各不相同，且与患者预后相关。这些酶的特定分布也与预后有关。这一系列发现增进了我们对NTIS病理生理学的理解，并可能为预后评估提供有价值的信息。
