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格雷夫斯病活动期伴或不伴眼病患者 MMP-9 的相互作用。

Interaction of MMP-9 in the active phase of Graves' disease with and without ophthalmopathy.

机构信息

Endocrinology Division, Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, São Paulo, Brazil.

Department of Ophthalmology and Otorhinolaryngology, Faculty of Medical Sciences, University of Campinas, São Paulo, Brazil.

出版信息

Am J Physiol Endocrinol Metab. 2024 Oct 1;327(4):E577-E584. doi: 10.1152/ajpendo.00166.2024. Epub 2024 Sep 11.

Abstract

Thyroid eye disease (TED) is expressed as orbital inflammation, and serum levels of several proinflammatory cytokines have been studied among patients with Graves' disease (GD) with and without TED; however, a more sensitive and specific marker for the different phases of GD and TED is still lacking. Seventeen active TED, 16 inactive TED, 16 GD without TED, and 16 healthy controls were recruited. Serum IL-17A, MMP-2, MMP-3, and MMP-9 were measured by multiplex bead assay. TED hormone and eye parameters were evaluated, and their relationship with cytokine levels was analyzed. Serum MMP-9 was higher in active TED than healthy controls, whereas IL-17A was lower among these patients than in GD without TED and healthy controls. No differences were found in MMP-3 and MMP-2 concentrations. MMP-9 levels were lower in patients with inactive TED who underwent radioactive iodine (RAI) therapy and those on levothyroxine replacement. MMP-9 levels were elevated in patients on methimazole. A negative correlation was found between age at assessment and time of follow-up with MMP-9 levels in inactive TED. Free T3 and ophthalmometry values were positively correlated with MMP-9 in the GD without TED and inactive TED groups, respectively. In conclusion, serum MMP-9 was increased in patients with active TED and was related to the RAI treatment, longer follow-up time, and higher ophthalmometry in patients with inactive TED, as well as thyroid function in GD without TED. MMP-9 may be involved in both the active phase of TED and the active phase of inflammation related to GD. Our study addresses clinical aspects of specific ophthalmological examination and serum cytokine concentrations of patients with Graves' disease (GD) with and without ophthalmopathy. Our findings suggest that MMP-9 may be involved in the active phase of ophthalmopathy and in the active phase of GD. The central question is whether MMP-9 is a potential target for future treatments.

摘要

甲状腺眼病(TED)表现为眼眶炎症,已有研究检测 Graves 病(GD)伴或不伴 TED 患者的几种促炎细胞因子的血清水平;然而,对于 GD 和 TED 的不同阶段,仍然缺乏更敏感和特异的标志物。本研究纳入了 17 例活动性 TED、16 例静止性 TED、16 例 GD 无 TED 和 16 名健康对照者。通过多重微球检测法测量血清白细胞介素 17A(IL-17A)、基质金属蛋白酶 2(MMP-2)、基质金属蛋白酶 3(MMP-3)和基质金属蛋白酶 9(MMP-9)。评估 TED 激素和眼部参数,并分析其与细胞因子水平的关系。与健康对照组相比,活动性 TED 患者的血清 MMP-9 更高,而这些患者的 IL-17A 低于 GD 无 TED 患者和健康对照组。MMP-3 和 MMP-2 浓度无差异。接受放射性碘(RAI)治疗和甲状腺素替代治疗的静止性 TED 患者的 MMP-9 水平较低。甲巯咪唑治疗患者的 MMP-9 水平升高。与静止性 TED 患者相比,年龄和随访时间与 MMP-9 水平呈负相关。GD 无 TED 和静止性 TED 组游离三碘甲状腺原氨酸(FT3)和眼参数值与 MMP-9 呈正相关。结论:活动性 TED 患者的血清 MMP-9 升高,与 RAI 治疗、随访时间延长以及静止性 TED 患者眼参数升高有关,与 GD 无 TED 患者的甲状腺功能有关。MMP-9 可能参与 TED 的活动期和与 GD 相关的活动期炎症。本研究探讨了伴有和不伴眼病的 Graves 病(GD)患者的特定眼科检查和血清细胞因子浓度的临床方面。我们的研究结果表明,MMP-9 可能参与眼病的活动期和 GD 的活动期。核心问题是 MMP-9 是否是未来治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf6a/11482230/58d531a3c871/e-00166-2024r01.jpg

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