Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University Hospital Center Zagreb, Zagreb, Croatia.
Pediatric Clinic, Children's Hospital Zagreb, Zagreb, Croatia.
Front Endocrinol (Lausanne). 2024 Jul 23;15:1335371. doi: 10.3389/fendo.2024.1335371. eCollection 2024.
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.
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.
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.
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.
我们比较了患有 1 型糖尿病（T1D）或肥胖症（OB）（均涉及炎症和血管并发症）的儿童和青少年外周血（PBL）趋化因子配体/受体谱，以确定它们与心血管代谢危险因素的关联。
儿童和青少年（12-18 岁）的 PBL 样本包括：健康对照组（n=29）、T1D 患者（n=31）和 OB 受试者（n=34）。通过流式细胞术测定单核细胞群体和趋化因子受体表达（CCR2、CCR4、CXCR3、CXCR4）的频率。通过基于珠子的测定法测量趋化因子 CCL2、CCL5、CXCL10 和 CXCL11 的水平，并通过 ELISA 测量 CXCL12 的水平。将数据与心血管、代谢和炎症参数相关联。
T1D 患者中 CD14 单核细胞的比例较高，而 OB 患者中 CD19 B 淋巴细胞的比例较高，CD3 T 淋巴细胞的比例较低。T1D 患者中 CCL2 的水平较高（T1D 中 241.0（IQR 189.6-295.3）pg/mL，对照组中 191.5（IQR 158.0-254.7）pg/mL，p=0.033），OB 患者中 CXCL11 的水平较低（OB 中 6.6（IQR 4.9-7.7）pg/mL，对照组中 8.2（IQR 6.9-11.3）pg/mL，p=0.018），两种疾病中 CXCL12 的水平均较低（T1D 中 2.0（IQR 1.8-2.5）ng/mL，OB 中 2.1（IQR 1.9-2.4）ng/mL，对照组中 2.4（IQR 2.2-2.5）ng/mL，p=0.016）。趋化因子配体/受体谱与临床数据之间存在许多显著关联。在这些关联中，我们提出了 T1D 中心血管代谢风险的最重要指标：CCR2 单核细胞与血压的正相关，CCL12 水平与尿白蛋白/肌酐比值（ACR）的正相关，CXCR3 B 淋巴细胞与 AST 的负相关，但与甘油三酯的正相关；OB：CXCL12 水平与甘油三酯和 AST/ALT 的正相关，CCR4 和 CXCR3 单核细胞与 ACR 的负相关。两种疾病均显示 CCR4 T 淋巴细胞和血压的正相关，CCR4 亚群与 ACR 和 CXCR3 T 淋巴细胞与脂质谱的负相关。
即使在儿童和青少年时期，T1D 和 OB 也存在明显改变的趋化因子配体/受体谱。尽管与心血管代谢危险因素的关联不同表明存在疾病特异性变化，但在 CCR4 T 淋巴细胞与血管炎症、CCR4 亚群与白蛋白尿以及 CXCR3 T 淋巴细胞与血脂异常之间发现了重叠模式。因此，趋化因子轴可能是治疗与疾病相关发病率的潜在治疗靶点。
