IgG4相关性眼病研究进展

IgG4相关性疾病是一种近几年才被认识的疾病,病因尚不明确。以同时或逐步出现的一种或多种组织和器官中大量IgG4阳性淋巴浆细胞浸润、席纹状纤维化、闭塞性静脉炎为特征,可伴有血清IgG4水平升高。当累及眼部时称为IgG4相关性眼病。任何眼附属器均可受累,多见于泪腺、眼眶脂肪、眶下神经、眼外肌和眼睑。本文将对近年来IgG4相关性眼病的流行病学特点、病理特点、临床表现、影像特点、诊断和治疗方面的最新进展作一综述。     

IgG4相关性眼病和眼附属器黏膜相关淋巴组织淋巴瘤的关系研究进展

IgG4相关性眼病是近期被认识的一种良性淋巴增生性疾病。眼附属器黏膜相关淋巴组织(MALT)淋巴瘤是一种低度恶性淋巴细胞肿瘤。这2种疾病的临床特征有诸多相似性,为诊断和治疗带来一定困难,需要仔细鉴别。此外,近年来的研究发现这2种眼部疾病之间存在潜在联系,部分IgG4相关性眼病有可能进展为MALT淋巴瘤。因此,本文就2种疾病的对比以及相关性研究的最新进展做一综述。     

IgG4相关性眼病的诊疗研究进展

免疫球蛋白G4(IgG4)相关性疾病(IgG4-RD)是近年来受关注度较高的一类慢性、系统性疾病。IgG4-RD可累及全身各个组织,主要表现为累及器官的肿胀及占位改变,当病变侵犯至眼部周围时称为IgG4相关性眼病(IgG4-ROD),主要侵犯泪腺、眼眶脂肪、眶下神经、眼外肌和眼睑等。目前,针对IgG4-ROD的主要治疗方式有药物治疗、手术、放射治疗等。随着近年对该病认识的不断提升,治疗有效率不断提高,本文就IgG4-ROD的流行病学特点、临床表现、影像特点、诊断和治疗的最新进展进行综述。     

IgG4相关性眼病与眼附属器淋巴瘤的关系及鉴别

IgG4相关性眼病(immunoglobulinG4-related ophthalmic disease,IgG4-ROD)是一种较为常见的眼部疾病,可以发展为淋巴瘤,但发生机制未明。眼附属器淋巴瘤是成年人最常见的发生于眼部的恶性肿瘤。IgG4-ROD和眼附属器淋巴瘤的临床表现和影像学特征具有相似性,故仅凭临床表现和...     

IgG4相关眼病的机制及诊疗研究进展

IgG4相关疾病(IgG4-RD)是一种新近被认识的与IgG4淋巴细胞密切相关的慢性、系统性疾病。累及眼部时,命名为IgG4眼部相关疾病(IgG4-ROD)。IgG4-ROD临床表现受侵犯部位影响,与其他累及器官相比具有独特的病理特征。随着近年对该疾病临床认识的深入,诊疗率不断提高。本文对IgG4-ROD的概念、流行病学、病因及发病机制、临床表现、组织病理学、影像学检查、实验室检查、诊断与鉴别诊断,以及治疗方面的研究进展进行综述。     

IgG4相关性疾病眼部病变的临床及影像学特征分析

目的 探讨IgG4相关性疾病眼部病变的临床及影像学特征。设计 回顾性病例系列。研究对象 25例在2010年10月-2014年5月期间首诊于眼科并经实验室和（或）活组织检查证实的IgG4相关性疾病患者。方法 回顾性分析25例患者眼部病变的临床及影像学表现。主要指标 临床表现,眼眶MRI,生长抑素受体SPECT/CT显像（SRS）。结果 25例患者双眼睑肿胀、眼球突出为主要临床表现,其中23例为双眼受累,22例患者有≥2个器官受累,眼外受累器官多见于鼻部（19例）和涎腺（13例）。眼眶MRI主要表现为弥漫性泪腺增大（22例）、眼外肌增粗（14例）、眶周软组织浸润（10例）等。SRS显示治疗前眼眶摄取示踪剂显著增高（UR=1.87±0.43）;经免疫抑制治疗后活动期眼眶示踪剂摄取减少（UR=1.51±0.24）。结论 IgG4相关性疾病的眼部病变具有较典型的临床特征,泪腺弥漫性增大为眼眶MRI最常见表现,SRS能客观反映受累眼眶的免疫活动程度,对临床疗效评价有较好的价值。 （眼科,2015, 24： 309-312）       

首诊于眼科的IgG4相关疾病初步研究

目的 对一组首诊于眼科的IgG4相关疾病患者进行总结分析.方法 回顾性病例分析.选取2011年1月～2021年4月解放军总医院第一医学中心神经眼科住院治疗的9例IgG4相关眼病(IgG4-ROD)纳入分析.总结患者临床表现、实验室检查、眼眶磁共振成像(MRI)、病理学检查和治疗情况.结果 9例患者,男性6例、女性3例,...     

IgG4相关性眼病研究进展

IgG4相关性眼病是一种与IgG4密切相关的慢性系统性疾病,是以血清IgG4水平升高及IgG4阳性浆细胞浸润泪腺、眼外肌、眶下神经等眼部附属器为特征,而且经常是全身系统性病变的首发症状.糖皮质激素对该病治疗有效.本文就近年来IgG4相关性眼病的病因发病机制,临床表现,诊断及治疗方面的最新进展进行综述.     

IgG4相关眼病三例

1例主诉为左眼视力下降1周;1例主诉为右眼视力减退2个月、结膜水肿10余天;1例主诉为双眼红肿1年,纳差、乏力4个月患者分别就诊眼科。3例患者均为男性,眼部检查均为双眼受累,2例表现为双眼泪腺肿大伴有球结膜水肿,1例为双眼眼睑肿胀,3例均伴有眶外组织受累,均诊断为IgG4相关眼病。经糖皮质激素冲击治疗后患者症状均好转,...     

国人甲状腺相关眼病患者血清免疫球蛋白4水平的研究

目的通过检测甲状腺相关眼病（TAO）患者血清IgG4和IgG的水平,探究IgG4与TAO之间的关系。方法前瞻性病例对照研究。分析和比较在第二军医大学附属长征医院眼科2014年9月至2015年7月期间收治的88例TAO患者和37例对照组的血清IgG4和IgG检测结果,研究IgG4和TAO临床指标之间的关联性。结果TAO活动期组的IgG4水平显著高于TAO静止期组（P=0．046）以及对照组（P=0．021）;TAO静止期组和对照组的IgG4水平差异无统计学意义（P=0．963）。TAO活动期组血清IgG4升高（IgG4≥135mg／dL）的比例显著高于静止期组（P=0．003）和对照组（P=0．007）;TAO静止期组和对照组之间差异无统计学意义（P=0．896）。TAO活动期组IgG4／IgG增加（IgG4／IgG8．0％）的比例显著高于静止期组（P=0．023）以及对照组（P=0.017）,但TAO静止期组和对照组之间差异无统计学意义（P=0．756）。CAS为血清IgG4水平的独立影响因素（P=0.021）。IgG4与性别、年龄、TAO病程、突眼度、CAS和严重程度之间均无线性相关性（P值分别为0．767、0.469、0．335、0．385、0．281和0．527）。结论部分TAO活动期患者血清IgG4水平、IgG4／IgG显著升高,并与CAS有关,提示TAO发病机制的异质性可能。     

IgG4-related orbital disease masquerading as thyroid eye disease,vice versa,or both?

A 40 year-old male presented after one year of unilateral, progressive, steroid-responsive, orbital inflammatory disease causing proptosis, extraocular muscle (EOM) restriction, and compressive optic neuropathy. The development of anti-thyroidal antibodies prompted the diagnosis of thyroid eye disease (TED); however, the prolonged active phase, remarkable reversibility of ophthalmic features with high-dose corticosteroids, unilaterally of disease, uncharacteristic EOM involvement (including both obliques), and the absence of autoimmune thyroid disease provoked consideration of alternative diagnoses. Inferior oblique biopsy stained positive for IgG4 with histologic features atypical of TED. The patient received rituximab for presumed IgG4-related orbital disease (IgG4-ROD) with subsequent reversal of compressive optic neuropathy, near complete resolution of EOM restriction, and improved proptosis, the latter two of which are not routinely anticipated in advanced TED. The possible role for B-cell depletion in both TED and IgG4-ROD suggests a degree of overlap in the underlying immune-related pathophysiology that is yet to be defined.     

A clinicopathological study on IgG4-related ophthalmic disease

AIM: To investigate clinicopathological features of immunoglobulin G4-related ophthalmic disease (IgG4-ROD), and analyze the recurrence rates following systemic corticosteroid administration. METHODS: We retrospectively searched clinical features, laboratory and histological findings based on the medical records of 21 patients with IgG4-ROD. All the patients examined in this study underwent surgical resection in the ocular adnexal lesions and underwent histological evaluation. This study further investigated clinical and histopathological features of 15 patients who received systemic corticosteroid after the resection. RESULTS: The mean age of the patients consisting of 7 males (33%) and 14 females (67%) was 61y. Fourteen patients were diagnosed as definitive, and 2 and 5 patients were probable and possible IgG4-ROD, respectively. Eyelid swelling was an initial symptom in 11 patients (52%) who did not show systemic involvements at a diagnosis. Fifteen patients received systemic corticosteroid administration, and all showed remission of inflammation. Among them, 10 patients did not recur, whereas 5 patients (33%) recurred during tapering. There were no significant difference between patients with or without recurrence in clinicopathological features. CONCLUSION: In this study, female patients are more predominant in IgG4-ROD. While inflammation recurs in one-third of patients, this study do not identify factors associated with recurrence after systemic corticosteroid administration.     

The impact of IgG-4-ROD on the diagnosis of orbital tumors: A retrospective analysis

This study was to determine the prevalence of immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD) among patients who have previously undergone biopsy and were diagnosed to have idiopathic orbital inflammatory disease (IOID) or orbital lymphoproliferative disease (OLD), namely, lymphoma and benign reactive lymphoid hyperplasia (BRLH). This is a retrospective cross-sectional study. The charts and slides of all patients who underwent biopsies and were histopathologically diagnosed to have either IOID or OLD were reviewed. Demographics, clinical features, initial histopathological diagnoses, treatment received, and final outcome were noted. Using the diagnostic criteria for diagnosis for IgG4 disease, those cases that would classify as “possible IgG4-related disease (IgG4-RD)” were reviewed, reclassified, and reassigned a diagnosis of IgG4-ROD. We reviewed 105 patients’ clinical charts. Of these 105 patients, upon reviewing the histopathology, 18 (17.15%) patients were found to fit the diagnostic criteria for possible IgG4-ROD. Of these 18 patients who were now reassigned the diagnosis of IgG4-ROD, the most common previous histopathological diagnosis was found to be IOID, for eight patients (44%), then BRLH, which was noted in five patients (27.8%), followed by lymphoma, which was noted in two patients (11.1%). Previously diagnosed cases of IOID and OLD were found to fulfill the criteria for IgG4-ROD. Given the advent of recent diagnostic and histopathological techniques, all cases of suspected IOID and OLD should be screened for IgG4-ROD and all previously diagnosed cases must be closely followed up, given the systemic implication of IgG4-RD. Histopathological reassessment of previously diagnosed cases may be considered.     

The Case of IgG4-related Ophthalmic Disease Accompanied by Compressive Optic Neuropathy

A 76-year-old woman was diagnosed with thyroid-associated orbitopathy (TAO) associated with hypothyroidism at another clinic. Magnetic resonance imaging showed enlargements of the extraocular muscles. Because her best-corrected visual acuity (BCVA) was 0.01OD, she was referred to the Chiba University Hospital. She had an elevation of serum IgG4. She was diagnosed with possible IgG4-related ophthalmic disease (IgG4-ROD) accompanied by optic nerve compression with the mass. She underwent methylprednisolone pulse therapy, and, two months later, her BCVA and visual field defect were greatly improved. Our findings indicate that ophthalmologists should be aware that IgG4-ROD can be masked by lesions associated with TAO.     

Differential Tissue Metabolic Signatures in IgG4-Related Ophthalmic Disease and Orbital Mucosa-Associated Lymphoid Tissue Lymphoma

PurposeTo identify tissue metabolomic profiles in biopsy specimens with IgG4-related ophthalmic disease (IgG4-ROD) and mucosa-associated lymphoid tissue (MALT) lymphoma and investigate their potential implication in the disease pathogenesis and biomarkers.MethodsWe conducted a comprehensive analysis of the metabolomes and lipidomes of biopsy-proven IgG4-ROD (n = 22) and orbital MALT lymphoma (n = 21) specimens and matched adjacent microscopically normal adipose tissues using liquid chromatography time-of-flight mass spectrometry. The altered metabolomic profiles were visualized by heat map and principal component analysis. Metabolic pathway analysis was performed by Metabo Analyst 4.0 using differentially expressed metabolites. The diagnostic performance of the metabolic markers was evaluated using receiver operating characteristic curves. Machine learning algorithms were implemented by random forest using the R environment. Finally, an independent set of 18 IgG4-ROD and 17 orbital MALT lymphoma specimens were used to validate the identified biomarkers.ResultsThe principal component analysis showed a significant difference of both IgG4-ROD and orbital MALT lymphoma for biopsy specimens and controls. Interestingly, lesions in IgG4-ROD were uniquely enriched in arachidonic metabolism, whereas those in orbital MALT lymphoma were enriched in tricarboxylic acid cycle metabolism. We identified spermine as the best discriminator between IgG4-ROD and orbital MALT lymphoma, and the area under the receiver operating characteristic curve of the spermine to discriminate between the two diseases was 0.89 (95% confidence interval, 0.803–0.984). A random forest model incorporating a panel of five metabolites showed a high area under the receiver operating characteristic curve value of 0.983 (95% confidence interval, 0.981–0.984). The results of validation revealed that four tissue metabolites: N¹,N¹²-diacetylspermine, spermine, malate, and glycolate, had statistically significant differences between IgG4-ROD and orbital MALT lymphoma with receiver operating characteristic values from 0.708 to 0.863.ConclusionsThese data revealed the characteristic differences in metabolomic profiles between IgG4-ROD and orbital MALT lymphoma, which may be useful for developing new diagnostic biomarkers and elucidating the pathogenic mechanisms of these common orbital lymphoproliferative disorders.     

基质蛋白Fibulin-5在眼眶IgG4相关性疾病中的表达

目的　探讨基质蛋白Ｆｉｂｕｌｉｎ-５与眼眶ＩｇＧ４相关性疾病（ＩｇＧ４-ｒｅｌａｔｅｄｏｃｕｌａｒｄｉｓ-ｅａｓｅ,ＩｇＧ４-ＲＯＤ）纤维化、炎症、硬化的关系。方法　收集２０例（２０眼）眼眶开放性粉碎性骨折清创术中采集的正常泪腺组织标本作为对照组,２０例（２０眼）眼眶ＩｇＧ４-ＲＯＤ患者的泪腺肿物作为ＩｇＧ４-ＲＯＤ组,采用免疫组织化学染色结合图像分析法对基质蛋白Ｆｉｂｕｌｉｎ-５进行半定量分析,采用实时荧光定量ＰＣＲ和Ｗｅｓｔｅｒｎ-ｂｌｏｔｔｉｎｇ法检测Ｆｉｂｕｌｉｎ-５ｍＲＮＡ及蛋白的相对表达量。结果　ＩｇＧ４-ＲＯＤ组中Ｆｉｂｕｌｉｎ-５ｍＲＮＡ的表达水平为３．６９±１．７２,显著高于对照组（１．６９±０．４５）,两组比较差异有统计学意义（Ｐ＜０．０５）。Ｆｉｂｕｌｉｎ-５蛋白与Ｆｉｂ-ｕｌｉｎ-５ｍＲＮＡ表达变化趋势较为一致。ＩｇＧ４-ＲＯＤ组中Ｆｉｂｕｌｉｎ-５蛋白的表达水平为０．５５±０．１２,对照组中Ｆｉｂｕｌｉｎ-５蛋白表达水平为０．１９±０．１１,两组比较差异有统计学意义（Ｐ＜０．０１）。免疫组织化学结果显示,ＩｇＧ４-ＲＯＤ组中泪腺细胞排列不规则,染色为黄色、棕黄色的纤维化细胞排列紊乱,对照组中泪腺腺管规则,细胞规则排列,核染蓝色。ＩｇＧ４-ＲＯＤ组Ｆｉｂｕｌｉｎ-５蛋白的阳性表达显著高于对照组。结论　ＩｇＧ４-ＲＯＤ组中Ｆｉｂｕｌｉｎ-５ｍＲＮＡ和蛋白表达较对照组显著升高,Ｆｉｂｕｌｉｎ-５可能促进眼眶ＩｇＧ４-ＲＯＤ的纤维化及硬化。     

Orbital progressive transformation of germinal centers as part of the spectrum of IgG4-related ophthalmic disease: Clinicopathologic features of three cases

Progressive transformation of germinal centers (PTGC) is a form of follicular hyperplasia recently associated with immunoglobulin G4-related disease (IgG4-RD), but the ophthalmic manifestations of this combination are poorly described. In this retrospective case series, we present three cases of IgG4-related orbital disease (IgG4-ROD) showing varying degrees of PTGC involving the orbit and lacrimal gland. Three adult women presented with ill-defined lacrimal gland enlargement. Histologic sections showed variable fibrosis and large, irregular lymphoid follicles with prominent mantle zones penetrating the germinal centers, highlighted by Bcl-2 and/or IgD immunostains. The interfollicular areas contained a mixture of plasma cells, scattered histiocytes and eosinophils. Mixed T and B-cells were present, and no signs of monoclonality were identified. All cases showed more than 100 IgG4 positive cells per high power field. Epstein-Barr virus in situ hybridization performed in one case was negative. The serum IgG4 level was tested in one case and showed elevation above the normal range. After 2–10?months of follow-up, the patients showed either near-complete resolution or no remaining signs of ophthalmic disease. Increasing awareness of these PTGC in extra-nodal locations, including the orbit, may provide a better understanding of the histologic spectrum of this disease.     

IgG4-related ophthalmic disease

IgG4-related disease is a fibro-inflammatory condition with tendency to form tumors with inflammatory infiltrate with IgG4 rich plasma cells and elevation of IgG4 level in serum, which may affect virtually every organ and tissue in the organism. IgG4-related ophthalmic disease may present as dacryoadenitis, myositis, other orbital tissues, hypophysitis or pachymeningitis causing cranial neuropathies. The diagnosis of IgG4-related disease is based on a typical clinical scenario, supportive laboratory data, expected radiological characteristics and distinct histopathological and immunohistochemical features. Corticosteroid followed by the use of long-term immunosuppressive therapy is the most commonly attempted treatment.