PDF(Pubmed)
Abstract：
UNASSIGNED: We compared peripheral blood (PBL) chemokine ligand/receptor profiles in children and adolescents with type 1 diabetes mellitus (T1D) or obesity (OB) (both involving inflammation and vascular complications) to identify their associations with cardiometabolic risk factors.
UNASSIGNED: PBL samples from children and adolescents (12-18 years) included: healthy controls (n=29), patients with T1D (n=31) and OB subjects (n=34). Frequency of mononuclear cell populations and chemokine receptor expression (CCR2, CCR4, CXCR3, CXCR4) were determined by flow cytometry. Chemokine levels of CCL2, CCL5, CXCL10 and CXCL11 were measured by bead-based assay and CXCL12 by ELISA. Data were correlated with cardiovascular, metabolic and inflammatory parameters.
UNASSIGNED: The proportion of CD14+ monocytes was higher in T1D, whereas the proportion of CD19+ B lymphocytes was higher and CD3+ T lymphocytes was lower in OB. The level of CCL2 was higher in T1D (241.0 (IQR 189.6-295.3) pg/mL in T1D vs 191.5 (IQR 158.0-254.7) pg/mL in control, p=0.033), CXCL11 was lower in OB (6.6 (IQR 4.9-7.7) pg/mL in OB vs 8.2 (IQR 6.9-11.3) pg/mL in control, p=0.018) and CXCL12 was lower in both diseases (2.0 (IQR 1.8-2.5) ng/mL in T1D, 2.1 (IQR 1.9-2.4) ng/mL in OB vs 2.4 (IQR 2.2-2.5) ng/mL in control, p=0.016). Numerous significant associations were found for chemokine ligand/receptor profiles and clinical data. Among these, we are suggesting the most important indicators of cardiometabolic risk in T1D: positive associations of CCR2+ monocytes with blood pressure and CCL12 levels with urine albumin-to-creatinine ratio (ACR), inverse association of CXCR3+ B lymphocytes with AST but positive with triglycerides; and OB: positive associations of CXCL12 levels with triglycerides and AST/ALT, inverse association of CCR4+ and CXCR3+ monocytes with ACR. Both diseases share positive associations for CCR4+ T lymphocytes and blood pressure, inverse associations of CXCR4+ subsets with ACR and CXCR3+ T lymphocytes with lipid profile.
UNASSIGNED: Significantly changed chemokine ligand/receptor profiles were found in both T1D and OB even at a young age. Although different associations with cardiometabolic risk factors indicate disease-specific changes, overlapping pattern was found for the associations between CCR4+ T lymphocytes and vascular inflammation, CXCR4+ subsets and albuminuria as well as CXCR3+ T lymphocytes and dyslipidemia. Thus, chemokine axes might present potential therapeutic targets for disease-related morbidity.
UNASSIGNED: PBL samples from children and adolescents (12-18 years) included: healthy controls (n=29), patients with T1D (n=31) and OB subjects (n=34). Frequency of mononuclear cell populations and chemokine receptor expression (CCR2, CCR4, CXCR3, CXCR4) were determined by flow cytometry. Chemokine levels of CCL2, CCL5, CXCL10 and CXCL11 were measured by bead-based assay and CXCL12 by ELISA. Data were correlated with cardiovascular, metabolic and inflammatory parameters.
UNASSIGNED: The proportion of CD14+ monocytes was higher in T1D, whereas the proportion of CD19+ B lymphocytes was higher and CD3+ T lymphocytes was lower in OB. The level of CCL2 was higher in T1D (241.0 (IQR 189.6-295.3) pg/mL in T1D vs 191.5 (IQR 158.0-254.7) pg/mL in control, p=0.033), CXCL11 was lower in OB (6.6 (IQR 4.9-7.7) pg/mL in OB vs 8.2 (IQR 6.9-11.3) pg/mL in control, p=0.018) and CXCL12 was lower in both diseases (2.0 (IQR 1.8-2.5) ng/mL in T1D, 2.1 (IQR 1.9-2.4) ng/mL in OB vs 2.4 (IQR 2.2-2.5) ng/mL in control, p=0.016). Numerous significant associations were found for chemokine ligand/receptor profiles and clinical data. Among these, we are suggesting the most important indicators of cardiometabolic risk in T1D: positive associations of CCR2+ monocytes with blood pressure and CCL12 levels with urine albumin-to-creatinine ratio (ACR), inverse association of CXCR3+ B lymphocytes with AST but positive with triglycerides; and OB: positive associations of CXCL12 levels with triglycerides and AST/ALT, inverse association of CCR4+ and CXCR3+ monocytes with ACR. Both diseases share positive associations for CCR4+ T lymphocytes and blood pressure, inverse associations of CXCR4+ subsets with ACR and CXCR3+ T lymphocytes with lipid profile.
UNASSIGNED: Significantly changed chemokine ligand/receptor profiles were found in both T1D and OB even at a young age. Although different associations with cardiometabolic risk factors indicate disease-specific changes, overlapping pattern was found for the associations between CCR4+ T lymphocytes and vascular inflammation, CXCR4+ subsets and albuminuria as well as CXCR3+ T lymphocytes and dyslipidemia. Thus, chemokine axes might present potential therapeutic targets for disease-related morbidity.
摘要：
■我们比较了患有1型糖尿病(T1D)或肥胖(OB)的儿童和青少年(包括炎症和血管并发症)的外周血(PBL)趋化因子配体/受体谱，以确定它们与心脏代谢危险因素的关系。
■来自儿童和青少年（12-18岁）的PBL样本包括：健康对照（n=29），T1D患者（n=31）和OB受试者（n=34）。通过流式细胞术确定单核细胞群体和趋化因子受体表达(CCR2、CCR4、CXCR3、CXCR4)的频率。CCL2、CCL5、CXCL10和CXCL11的趋化因子水平通过基于珠的测定法测量,CXCL12通过ELISA测量。数据与心血管相关，代谢和炎症参数。
■T1D中CD14+单核细胞比例较高,而OB中CD19+B淋巴细胞比例较高，CD3+T淋巴细胞比例较低。T1D中CCL2的水平较高（T1D中的241.0（IQR189.6-295.3）pg/mL，而对照组中的191.5（IQR158.0-254.7）pg/mL，p=0.033),OB中CXCL11较低（OB中6.6（IQR4.9-7.7）pg/mL，对照组中8.2（IQR6.9-11.3）pg/mL，p=0.018）和CXCL12在两种疾病中均较低（T1D中2.0（IQR1.8-2.5）ng/mL，OB中的2.1（IQR1.9-2.4）ng/mL与对照组中的2.4（IQR2.2-2.5）ng/mL，p=0.016)。对于趋化因子配体/受体谱和临床数据,发现了许多显著的关联。其中,我们建议T1D中最重要的心脏代谢风险指标：CCR2+单核细胞与血压呈正相关，CCL12水平与尿白蛋白-肌酐比值（ACR）呈正相关，CXCR3+B淋巴细胞与AST呈负相关，但与甘油三酯呈阳性；OB：CXCL12水平与甘油三酯和AST/ALT呈正相关，CCR4+和CXCR3+单核细胞与ACR的逆相关。两种疾病都有CCR4+T淋巴细胞和血压的正相关，CXCR4+亚群与ACR和CXCR3+T淋巴细胞与血脂谱的负相关。
■即使在年轻时，在T1D和OB中也发现了显著改变的趋化因子配体/受体谱。尽管与心脏代谢危险因素的不同关联表明疾病特异性变化，发现CCR4+T淋巴细胞与血管炎症之间的关联重叠模式，CXCR4+亚群和蛋白尿以及CXCR3+T淋巴细胞和血脂异常。因此，趋化因子轴可能是疾病相关发病率的潜在治疗靶点.
■来自儿童和青少年（12-18岁）的PBL样本包括：健康对照（n=29），T1D患者（n=31）和OB受试者（n=34）。通过流式细胞术确定单核细胞群体和趋化因子受体表达(CCR2、CCR4、CXCR3、CXCR4)的频率。CCL2、CCL5、CXCL10和CXCL11的趋化因子水平通过基于珠的测定法测量,CXCL12通过ELISA测量。数据与心血管相关，代谢和炎症参数。
■T1D中CD14+单核细胞比例较高,而OB中CD19+B淋巴细胞比例较高，CD3+T淋巴细胞比例较低。T1D中CCL2的水平较高（T1D中的241.0（IQR189.6-295.3）pg/mL，而对照组中的191.5（IQR158.0-254.7）pg/mL，p=0.033),OB中CXCL11较低（OB中6.6（IQR4.9-7.7）pg/mL，对照组中8.2（IQR6.9-11.3）pg/mL，p=0.018）和CXCL12在两种疾病中均较低（T1D中2.0（IQR1.8-2.5）ng/mL，OB中的2.1（IQR1.9-2.4）ng/mL与对照组中的2.4（IQR2.2-2.5）ng/mL，p=0.016)。对于趋化因子配体/受体谱和临床数据,发现了许多显著的关联。其中,我们建议T1D中最重要的心脏代谢风险指标：CCR2+单核细胞与血压呈正相关，CCL12水平与尿白蛋白-肌酐比值（ACR）呈正相关，CXCR3+B淋巴细胞与AST呈负相关，但与甘油三酯呈阳性；OB：CXCL12水平与甘油三酯和AST/ALT呈正相关，CCR4+和CXCR3+单核细胞与ACR的逆相关。两种疾病都有CCR4+T淋巴细胞和血压的正相关，CXCR4+亚群与ACR和CXCR3+T淋巴细胞与血脂谱的负相关。
■即使在年轻时，在T1D和OB中也发现了显著改变的趋化因子配体/受体谱。尽管与心脏代谢危险因素的不同关联表明疾病特异性变化，发现CCR4+T淋巴细胞与血管炎症之间的关联重叠模式，CXCR4+亚群和蛋白尿以及CXCR3+T淋巴细胞和血脂异常。因此，趋化因子轴可能是疾病相关发病率的潜在治疗靶点.
