新型炎症标志物与甲状腺相关性眼病活动性的相关性研究

Study on the correlation between novel inflammatory markers and the activity of thyroid-associated ophthalmopathy

摘要

目的 探讨新型炎症标志物单核细胞与高密度脂蛋白胆固醇比值（MHR）、全身免疫炎症指数（SII）与甲状腺相关性眼病（TAO）活动性的相关性。方法 回顾性分析2023年1月至2025年7月在华北理工大学附属医院内分泌与代谢病科住院治疗的84例TAO患者临床资料。根据临床活动性评分（CAS）分为活动性组（CAS≥3分）和非活动性组（CAS＜3分），收集2组一般资料、血常规、血生化、甲状腺功能、眼眶核磁共振（MRI）检查参数等指标。采用相关性分析、Logistic回归及受试者操作特征（ROC）曲线评估各指标的诊断价值。结果 二元Logistic回归分析提示，MHR、SII、EMA是TAO活动性患者的独立影响因素（均 P＜0.05）。ROC曲线分析提示，MHR对应的曲线下面积（AUC）值为0.679，95%CI为55.8%～80.0%， P=0.006，最佳界值为0.320，灵敏度为0.868，特异度为0.452；SII相应的AUC值为0.652，95%CI为53.1%～77.4%， P=0.020，最佳界值为0.298，灵敏度为0.717，特异度为0.581；联合诊断指标的AUC值为0.717，95%CI为60.8%～83.0%， P=0.001，最佳界值为0.429，灵敏度为0.623，特异度为0.806。结论 联合诊断指标的特异度最高，AUC值也相对较高，表明其在诊断TAO患者活动性方面具有较好的平衡性和较高的准确性。MHR与SII作为易获取的血液炎症标志物，可成为TAO活动性影像学评估的有效补充。MHR、SII及二者联合诊断指标可能成为评估TAO患者活动性的有价值指标。

Abstract

Objective To investigate the correlation between the novel inflammatory markers monocyte to high density lipoprotein cholesterol ratio (MHR), systemic immune inflammation index (SII) and the activity of thyroid associated ophthalmopathy (TAO). Methods The clinical data of 84 patients with TAO who were hospitalized in the Department of Endocrinology and Metabolic Diseases, the Affiliated Hospital of North China University of Science and Technology, from January 2023 to July 2025 were retrospectively analyzed. According to the clinical activity score (CAS), the patients were divided into the active group (CAS ≥ 3 points) and the inactive group (CAS ＜ 3 points). General data, routine blood test results, blood biochemical indicators, thyroid function, orbital magnetic resonance imaging (MRI) parameters, and other indicators were collected from the two groups. Correlation analysis, Logistic regression and receiver operating characteristic (ROC) curve analysis were used to evaluate the diagnostic value of each indicator. Results Binary Logistic regression analysis showed that MHR, SII and EMA were independent influencing factors for TAO activity ( P ＜ 0.05). ROC curve analysis showed that the area under the curve (AUC) for MHR was 0.679, with a 95% CI of 55.8%-80.0% and P = 0.006. The optimal cut off value was 0.320, with a sensitivity of 0.868 and a specificity of 0.452. The AUC for SII was 0.652, with a 95% CI of 53.1%-77.4% and P = 0.020. The optimal cut off value was 0.298, with a sensitivity of 0.717 and a specificity of 0.581. The AUC for the combined diagnostic indicator was 0.717, with a 95% CI of 60.8%-83.0% and P = 0.001. The optimal cut-off value was 0.429, with a sensitivity of 0.623 and a specificity of 0.806. Conclusions The combined diagnostic indicator had the highest specificity and a relatively high AUC, indicating that it has good balance and high accuracy in diagnosing activity in patients with TAO. As readily available blood inflammatory markers, MHR and SII may serve as effective supplements to imaging assessment and are correlated with TAO activity. MHR, SII and their combined diagnostic indicator may become valuable indicators for assessing activity in patients with TAO.

关键词

甲状腺相关性眼病 / 全身免疫炎症指数 / 单核细胞与高密度脂蛋白胆固醇比值 / 磁共振成像 / 临床活动性评分 / 生物标志物

Key words

Thyroid-associated ophthalmopathy / Systemic inflammatory index / Monocyte-to-high-density lipoprotein cholesterol ratio / Magnetic resonance imaging / Clinical activity score / Biomarker

参考文献

[1] HUANG J, CHEN M, LIANG Y, et al. Integrative metabolic analysis of orbital adipose/connective tissue in patients with thyroid-associated ophthalmopathy[J]. Int Arch Allergy Immunol, 2022, 13: 1001349. DOI: 10.3389/fendo.2022.1001349.

[2] LAI K K H, ALI ABDULLA ALJUFAIRI F M, LI C L, et al. Efficacy and safety of 6-weekly versus 12-weekly intravenous methylprednisolone in moderate-to-severe active thyroid-associated ophthalmopathy[J]. J Clin Med, 2023, 12(9): 3244. DOI: 10.3390/jcm12093244.

[3] MOURITS M P, KOORNNEEF L, WIERSINGA W M, et al. Clinical criteria for the assessment of disease activity in Graves' ophthalmopathy: a novel approach[J]. Br J Ophthalmol, 1989, 73(8): 639-644. DOI: 10.1136/bjo.73.8.639.

[4] JIANG M, YANG J, ZOU H, et al. Monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) and the risk of all-cause and cardiovascular mortality: a nationwide cohort study in the United States[J]. Lipds Health Dis, 2022, 21(1): 30. DOI: 10.1186/s12944-022-01638-6.

[5] TANG X, TAN Y, YANG Y, et al. Association of the monocyte-to-high-density lipoprotein cholesterol ratio with diabetic retinopathy[J]. Front Cardiovasc Med, 2021, 8: 707008. DOI: 10.3389/fcvm.2021.707008.

[6] MA R, CUI L, CAI J, et al. Association between systemic immune inflammation index, systemic inflammation response index and adult psoriasis: evidence from NHANES[J]. Front Immunol, 2024, 15: 1323174. DOI: 10.3389/fimmu.2024.1323174.

[7] 中华医学会眼科学分会眼整形眼眶病学组, 中华医学会内分泌学分会甲状腺学组. 中国甲状腺相关眼病诊断和治疗指南（2022年）[J]. 中华眼科杂志, 2022, 58(9): 646-668. DOI: 10.3760/cma.j.cn112142-20220421-00201.

[8] Oculoplastic and Orbital Disease Group of Chinese Ophthalmological Society of Chinese Medical Association, Thyroid Group of Chinese Society of Endocrinology of Chinese Medical Association. Chinese guideline on the diagnosis and treatment of thyroid-associated ophthalmopathy (2022)[J]. Chin J Ophthalmol, 2022, 58(9): 646-668. DOI: 10.3760/cma.j.cn112142-20220421-00201.

[9] MIAO T, LOU X, DONG S, et al. Monocyte-to-high-density lipoprotein-cholesterol ratio predicts prognosis of hepatocellular carcinoma in patients with metabolic-associated fatty liver disease[J]. J Hepatocell Carcinoma, 2024, 11: 145-157. DOI: 10.2147/JHC.S439397.

[10] LIU X, YAN G, XU B, et al. Association between monocyte-to-high-density lipoprotein-cholesterol ratio and gallstones in U. S. adults: findings from the National Health and Nutrition Examination Survey 2017-2020[J]. Lipids Health Dis, 2024, 23(1): 173. DOI: 10.1186/s12944-024-02166-1.

[11] MCLAREN J E, MICHAEL D R, SALTER R C, et al. IL-33 reduces macrophage foam cell formation[J]. J Immunol, 2010, 185(2): 1222-1229. DOI: 10.4049/jimmunol.1000520.

[12] TIAN W, QIU H, HE Y, et al. Qinghao-Biejia Herb Pair attenuates SLE atherosclerosis by regulating macrophage polarization via ABCA1/G1-mediated cholesterol efflux [J]. J Ethnopharmacol, 2024, 334: 118545. DOI: 10.1016/j.jep.2024.118545.

[13] 戎光, 周庆兵, 李婧, 等 . 化浊通脉方对ox-LDL诱导的RAW264.7来源泡沫细胞胆固醇逆转运相关基因表达作用研究[J]. 陕西中医, 2019, 40(12): 1664-1668. DOI: 10.3969/j.issn.1000-7369.2019.12.002.

[14] RONG G, ZHOU Q B, LI J, et al. Study on the effect of Huazhuo Tongmai recipe on ox-LDL-induced gene expression related to cholesterol reverse transport in RAW_264.7 foam cells [J]. Shaanxi J Tradit Chin Med, 2019, 40(12): 1664-1668. DOI: 10.3969/j.issn.1000-7369.2019.12.002.

[15] KıVRAKOĞLU F, ERGIN M, KOŞAR K . Evaluation of the systemic immune-inflammation index in relation to histological stages of celiac disease[J]. Eur J Med Res, 2025, 30(1): 694. DOI: 10.1186/s40001-025-02973-x.

[16] ZHENG H, YIN Z, LUO X, et al. Associations between systemic immunity-inflammation index and heart failure: Evidence from the NHANES 1999-2018[J]. Int J Cardiol, 2024, 395: 131400. DOI: 10.1016/j.ijcard.2023.131400.

[17] MAO L S, WANG Y X, WU Z M, et al. Elevated systemic immune-inflammatory index predicts poor coronary collateralization in type 2 diabetic patients with chronic total occlusion[J]. Front Cardiovasc Med, 2024, 11: 1490498. DOI: 10.3389/fcvm.2024.1490498.

[18] SUN H, LIANG J, XUE S, et al. Establishment and clinical application of a prognostic index for inflammatory status in triple-negative breast cancer patients undergoing neoadjuvant therapy using machine learning[J]. BMC Cancer, 2024, 24(1): 1559. DOI: 10.1186/s12885-024-13354-8.

[19] DI D, ZHOU H, CUI Z, et al. Frailty phenotype as mediator between systemic inflammation and osteoporosis and fracture risks: a prospective study[J]. J Cachexia Sarcopenia Muscle, 2024, 15(3): 897-906. DOI: 10.1002/jcsm.13447.

[20] SU Y, ZHANG X, JIANG J, et al. Association between the systemic immune-inflammation index and anemia among US children: national health and nutrition examination survey (NHANES), 2001-2018[J]. BMC Pediatr, 2025, 25(1): 588. DOI: 10.1186/s12887-025-05919-8.

[21] DENORME F, PORTIER I, RUSTAD J L, et al. Neutrophil extracellular traps regulate ischemic stroke brain injury[J]. J Clin Invest, 2022, 132(10): e154225. DOI: 10.1172/JCI154225.

[22] YETER V, KOÇAK N, ARSLAN M T, et al. Blood count-derived immunoinflammatory markers in thyroidassociated ophthalmopathy[J]. Korean J Ophthalmol, 2021, 35(3): 198-206. DOI: 10.3341/kjo.2021.0012.

[23] YUKSEL N, SARITAS O, YUKSEL E . Effect of thyroid hormone status on complete blood cell count-derived inflammatory biomarkers in patients with moderate-to-severe Graves' ophthalmopathy[J]. Int Ophthalmol, 2023, 43(9): 3355-3362. DOI: 10.1007/s10792-023-02742-x.

[24] ABOUNOORI M, POURAZIZI M, BAHMANI KASHKOULI M, et al. Novel immunoinflammatory blood markers in Graves’ orbitopathy: insights into activity and severity[J]. BMJ Open Ophthalmol, 2024, 9(1): e001744. DOI: 10.1136/bmjophth-2024-001744.

[25] YıLMAZ TUĞAN B, ERGEN A, ÖZKAN B . Monocyte-to-high-density lipoprotein ratio and systemic immune-inflammation index: Potential parameters for the evaluation of disease activity and severity in Graves' ophthalmopathy?[J]. Int Ophthalmol, 2024, 44(1): 154. DOI: 10.1007/s10792-024-03077-x.

[26] SUN X H, ZHANG X W, HAN C, et al. Monocyte to high-density lipoprotein cholesterol ratio as a predictor of the activity of thyroid-associated ophthalmopathy[J]. Int J Ophthalmol, 2024, 17(12): 2276-2281. DOI: 10.18240/ijo.2024.12.16.

[27] LE MOLI R, NASELLI A, PITICCHIO T, et al. The monocyte/HDLc ratio and LDLc are two independent predictors of the response of Graves’ ophthalmopathy patients to parenteral glucocorticoids[J]. Endocrine, 2025, 88(2): 545-552. DOI: 10.1007/s12020-025-04185-z.

[28] KARHANOVÁ M, ČIVRNÝ J, KALITOVÁ J, et al. Computed tomography and magnetic resonance imaging of the orbit in the diagnosis and treatment of thyroid-associated orbitopathy - experience from practice: a review[J]. Cesk Slov Oftalmol, 2023, 79(6): 283-292. DOI: 10.31348/2023/10.

[29] SULIMA I, MITERA B, SZUMOWSKI P, et al. Diagnosis of Graves' orbitopathy: imaging methods, challenges, and new perspectives[J]. Endokrynol Pol, 2025, 76(5): 469-477. DOI: 10.5603/ep.105785.

[30] RANA K, JUNIAT V, PATEL S, et al. Extraocular muscle enlargement[J]. Graefe’s Arch Clin Exp Ophthalmol, 2022, 260(11): 3419-3435. DOI: 10.1007/s00417-022-05727-1.

[31] ČIVRNÝ J, KARHANOVÁ M, HÜBNEROVÁ P, et al. MRI in the assessment of thyroid-associated orbitopathy activity[J]. Clin Radiol, 2022, 77(12): 925-934. DOI: 10.1016/j.crad.2022.08.124.

[32] DWIVEDI S N, KALARIA T, BUCH H . Thyroid autoantibodies[J]. J Clin Pathol, 2023, 76(1): 19-28. DOI: 10.1136/jcp-2022-208290.

[33] ZHAO S, SHI S, YANG W, et al. RhoA with associated TRAb or FT3 in the diagnosis and prediction of Graves' ophthalmopathy[J]. Dis Markers, 2022: 8323946. DOI: 10.1155/2022/8323946.

[34] GAO Y, QIU L, YU S, et al. Thyroid stimulating receptor autoantibodies[J]. Clin Chim Acta, 2024, 559: 119700. DOI: 10.1016/j.cca.2024.119700.

[35] MENG H, ZHOU X, LI L, et al. Monocyte to high-density lipoprotein cholesterol ratio predicts restenosis of drug-eluting stents in patients with unstable angina pectoris[J]. Sci Rep, 2024, 14: 30175. DOI: 10.1038/s41598-024-81818-9.

[36] CHEN B W, LIU J J, XING J H, et al. Analysis of the correlation between the ratio of monocytes to high-density lipoprotein cholesterol and in-stent restenosis in patients with premature coronary heart disease[J]. Clin Appl Thromb Hemost, 2022, 28: 10760296221079334. DOI: 10.1177/10760296221079334.

[37] LO J E, FREITAG S K, LIU C Y, et al. Long-term cardiovascular, renal, and safety outcomes of teprotumumab versus systemic glucocorticoids in thyroid eye disease a target trial emulation[J]. Ophthalmology, 2025, 132(10): 1142-1151. DOI: 10.1016/j.ophtha.2025.05.012.

基金资助

河北省医学科学研究课题计划(20250952)