甲状腺相关眼病免疫相关发病机制的研究现状与进展
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摘要
甲状腺相关眼病(thyroid associated ophthalmopathy,TAO)是Graves病最常见的甲状腺腺外表现,主要表现为上眼睑退缩、水肿、眶周组织红斑和眼球突出,进一步发展可影响患者视力甚至导致失明。TAO的发病机制不完全清楚,由多种因素共同影响,但是目前患者自身免疫的功能异常是TAO的主要发病因素。本文将从细胞免疫、自身抗原和自噬这几个方面阐述TAO免疫相关发病机制研究的现状与进展,为临床工作和相关研究提供参考。
Thyroid associated ophthalmopathy(TAO) is the most common extrathyroidal manifestation of Graves' disease,mainly manifested as upper eyelid retraction,edema,orbital tissue erythema and exophthalmos,and further development can affect the patient's vision and even lead to blindness.The pathogenesis of TAO is not completely clear and is affected by many factors.However,the abnormal function of autoimmunity is the main pathogenic factor of TAO.The current status and progress of TAO immune-related pathogenesis are reviewed in this article from the aspects of cellular immunity,autoantigen and autophagy,which can provide references for clinical work and related research.
Thyroid associated ophthalmopathy(TAO) is the most common extrathyroidal manifestation of Graves' disease,mainly manifested as upper eyelid retraction,edema,orbital tissue erythema and exophthalmos,and further development can affect the patient's vision and even lead to blindness.The pathogenesis of TAO is not completely clear and is affected by many factors.However,the abnormal function of autoimmunity is the main pathogenic factor of TAO.The current status and progress of TAO immune-related pathogenesis are reviewed in this article from the aspects of cellular immunity,autoantigen and autophagy,which can provide references for clinical work and related research.
引文
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[5] LIU F,ZHU Y,ZHANG K,LI Z G.Effect of pulsed glucocorticoid combined with orbital radiotherapy for the treatment of severe active thyroid associated ophthalmopathy[J].J Xin-xiang Med Univ,2016,33(7):623-625.刘芳,朱豫,张珂,李志刚.激素冲击联合放射治疗重度活动期甲状腺相关眼病疗效观察[J].新乡医学院学报,2016,33(7):623-625.
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[7] CHEN H H,TAO Y.Research progresses in the pathogenesis of thyroid associated ophthalmopathy[J].Chin J Pract Intern Med,2015,35(7):561-565.陈欢欢,涛杨.甲状腺相关眼病发病机制研究进展[J].中国实用内科杂志,2015,35(7):561-565.
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[12] RAPOPORT B,MCLACHLAN S M.Graves’ hyperthyroidism is antibody-mediated but is predominantly a Th1-type cytokine disease[J].J Clin Endocrinol Metab,2014,99(11):4060-4061.
[13] FANG S,HUANG Y,LIU X,ZHONG S,WANG N,ZHAO B,et al.Interaction between CCR6+ Th17 cells and CD34+ fibrocytes promotes inflammation:implications in Graves’ orbitopathy in chinese population[J].Invest Ophthalmol Vis Sci,2018,59(6):2604-2614.
[14] SIOMKAJ? O M,DYBKO J,DAROSZEWSKI J.Regulatory lymphocytes in thyroid orbitopathy and autoimmune thyroid diseases[J].Postepy Hig Med Dosw (Online),2016,70(0):1378-1388.
[15] BEDOYA S K,LAM B,LAU K,RD L J.Th17 cells in immunity and autoimmunity[J].Clin Dev Immunol,2013,2013(7):986789.
[16] ICHIYAMA K,GONZALEZ-MARTIN A,KIM B S,JIN H Y,JIN W,XU W,et al.The microRNA-183-96-182 cluster promotes T helper 17 cell pathogenicity by negatively regulating transcription factor Foxo1 expression[J].Immunity,2016,44(6):1284-1298.
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[18] MATSUZAWA K,IZAWA S,OKURA T,FUJII S,MATSUMOTO K,SHOJI K,et al.Implications of FoxP3-positive and -negative CD4+CD25+T cells in Graves’ ophthalmopathy[J].Endocr J,2016,63(8):755-764.
[19] RAMOS-LEVI A M,MARAZUELA M.Pathogenesis of thyroid autoimmune disease:the role of cellular mechanisms[J].Endocrinol Nutr,2016,63(8):421-429.
[20] HWANG C J,AFIFIYAN N,SAND D,NAIK V,SAID J,POLLOCK S J,et al.Orbital fibroblasts from patients with thyroid-associated ophthalmopathy overexpress CD40:CD154 hyperinduces IL-6,IL-8,and MCP-1[J].Invest Ophthalmol Vis Sci,2009,50(5):2262-2268.
[21] SALVI M.Immunotherapy for Graves’ ophthalmopathy[J].Curr Opin Endocrinol Diabetes Obes,2014,21(5):409-414.
[22] NAGATA K,NAKAYAMA Y,HIGAKI K,OCHI M,KANAI K,MATSUSHITA M,et al.Reactivation of persistent Epstein-Barr virus (EBV) causes secretion of thyrotropin receptor antibodies (TRAbs) in EBV-infected B lymphocytes with TRAbs on their surface[J].Autoimmunity,2015,48(5):328-335.
[23] KAMBAYASHI T,LAUFER T M.Atypical MHC class II-expressing antigen-presenting cells:can anything replace a dendritic cell?[J].Nat Rev Immunol,2014,14(11):719-730.
[24] TANG F,CHEN X,MAO Y,WAN S,AI S,YANG H,et al.Orbital fibroblasts of Graves’ orbitopathy stimulated with proinflammatory cytokines promote B cell survival by secreting BAFF[J].Mol Cell Endocrinol,2017,446:1-11.
[25] ROSSER E C,MAURI C.Regulatory B cells:origin,phenotype,and function[J].Immunity,2015,42(4):607-612.
[26] VAN DER WEERD K,VAN HAGEN PM,SCHRIJVER B,KWEK-KEBOOM D J,DE HERDER WW,TEN BROEK M R,et al.The peripheral blood compartment in patients with Graves’ disease:activated T lymphocytes and increased transitional and pre-naive mature B lymphocytes[J].Clin Exp Immunol,2013,174(2):256-264.
[27] SAHLI E,GUNDUZ K.Thyroid-associated ophthalmopathy[J].Turkish J Ophthalmol,2017,47(2):94-105.
[28] DIK W A,VIRAKUL S,VAN STEENSEL L.Current perspectives on the role of orbital fibroblasts in the pathogenesis of Graves’ ophthalmopathy[J].Exp Eye Res,2016,142:83-91.
[29] WANG Q,SHI B M,XIE F,FU Z Y,CHEN Y J,AN J N,et al.Enhancement of CD4+T cell response and survival via coexpressed OX40/OX40L in Graves’ disease[J].Mol Cell Endocrinol,2016,430:115-124.
[30] LI B,SMITH T J.Divergent expression of IL-1 receptor antagonists in CD34+ fibrocytes and orbital fibroblasts in thyroid-associated ophthalmopathy:contribution of fibrocytes to orbital inflammation[J].J Clin Endocrinol Metab,2013,98(7):2783-2790.
[31] DOUGLAS R S,AFIFIYAN N F,HWANG C J,CHONG K,HAIDER U,RICHARDS P,et al.Increased generation of fibrocytes in thyroid-associated ophthalmopathy[J].J Clin Endocrinol Metab,2010,95(1):430-438.
[32] FERNANDO R,LU Y,ATKINS S J,MESTER T,BRANHAM K,SMITH T J.Expression of thyrotropin receptor,thyroglobulin,sodium-iodide symporter,and thyroperoxidase by fibrocytes depends on AIRE[J].J Clin Endocrinol Metab,2014,99(7):E1236-1244.
[33] FERNANDO R,ATKINS S,RAYCHAUDHURI N,LU Y,LI B,DOUGLAS R S,et al.Human fibrocytes coexpress thyroglobulin and thyrotropin receptor[J].Proc Natl Acad Sci USA,2012,109(19):7427-7432.
[34] KRISS J P,PLESHAKOV V,ROSENBLUM A L,HOLDERNESS M,SHARP G,UTIGER R.Studies on the pathogenesis of the ophthalmopathy of Graves’ disease[J].J Clin Endocrinol Metab,1967,27(4):582.
[35] SMITH T J.TSH-receptor-expressing fibrocytes and thyroid-associated ophthalmopathy[J].Nat Rev Endocrinol,2015,11(3):171-181.
[36] LYTTON S D,PONTO K A,KANITZ M,MATHEIS N,KOHN L D,KAHALY GJ.A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves’ orbitopathy[J].J Clin Endocrinol Metab,2010,95(5):2123-2131.
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