摘要
目的:Graves病是一种以甲状腺激素分泌增多、甲状腺肿大及促甲状腺激素受体抗体(thyroid stimulating hormone receptor antibody,TRAb)阳性为特征的自身免疫性甲状腺疾病。免疫球蛋白(immunoglobulin,Ig)G4相关性疾病是一种慢性炎症伴纤维化的多系统疾病。部分Graves病患者存在血清IgG4水平升高,可能构成一种独特的临床亚型。本研究旨在探讨伴有IgG4升高的Graves病患者临床特征、实验室指标、治疗反应及长期预后,以提高对该亚型的识别与临床管理,为个性化治疗提供依据。方法:选取2021年6月至12月于中南大学湘雅三医院内分泌科确诊的159例初诊Graves病患者作为回顾性队列研究对象。依据血清IgG4水平将患者分为IgG4阳性组(≥2.01 g/L)和IgG4阴性组(<2.01 g/L)。收集2组患者基线临床资料、检测游离三碘甲腺原氨酸(free triiodothyronine,FT3)、游离甲状腺素(free thyroxine,FT4),促甲状腺激素(thyroid-stimulating hormone,TSH)、TRAb、甲状腺球蛋白抗体(thyroglobulin antibody,TGAb)、甲状腺过氧化物酶自身抗体(thyroid peroxidase autoantibody,TPOAb)、血清抗核抗体(antinuclear antibody,ANA)和抗可提取性核抗原(extractable nuclear antigens,ENA)抗体等自身免疫抗体指标,并在治疗后1、3、6、9、12及24个月进行随访,评估甲状腺功能与抗体水平变化。治疗满3年后通过电话随访记录停药率及复发率。结果:159例患者中IgG4阳性组26例,IgG4阴性组133例。与IgG4阴性组比较,IgG4阳性组Graves病患者血清IgG4水平明显升高,男性占比较高(均P<0.05);血清FT3、TPOAb、TGAb及球蛋白水平均较高,白球比较低(均P<0.05);不同滴度(1꞉80,1꞉160,1꞉320,1꞉1000)的ANA阳性率、ENA抗体谱中抗Sm抗体、抗SSA抗体、抗U1RNP自身抗体阳性率均较高(均P<0.05)。而2组Graves病患者的发病年龄、FT4、TSH及TRAb水平差异均无统计学意义(均P>0.05)。24例IgG4阳性组和93例阴性组完成治疗后随访,治疗后12个月IgG4阳性组患者TPOAb和TGAb水平均高于IgG4阴性组(均P<0.05);治疗后24个月IgG4阳性组患者FT3与FT4水平均高于IgG4阴性组(均P<0.05);治疗后3年IgG4阳性组停药率显著低于IgG4阴性组(47.62%vs 71.26%,P=0.039),复发率高于IgG4阴性组(28.57%vs 14.94%),但其差异无统计学意义(P=0.249)。结论:伴有IgG4水平升高的Graves病患者多见于男性,具有更高的FT3及甲状腺自身抗体水平和更活跃的系统性自身免疫状态,可能与干燥综合征、系统性红斑狼疮等其他自身免疫病存在关联。该亚型停药率低、复发倾向高,提示其临床过程更为迁延,预后较差。建议在临床中加强对这类患者的识别与长期随访,个体化调整治疗策略,并关注其潜在的多系统免疫异常。
Objective:Graves’disease(GD)is an autoimmune thyroid disorder characterized by hyperthyroidism,goiter,and positivity for thyroid-stimulating hormone receptor antibodies(TRAb).A subset of patients present with elevated immunoglobulin G4(IgG4)levels,which may represent a distinct clinical subtype.This study aims to investigate the clinical features,laboratory parameters,treatment response,and long-term prognosis of GD patients with elevated IgG4 levels to improve recognition and provide a basis for individualized management.Methods:A retrospective cohort study was conducted on 159 newly diagnosed GD patients admitted to Xiangya Third Hospital of Central South University between June and December 2021.Patients were divided into an IgG4-positive(≥2.01 g/L)and an IgG4-negative group(<2.01 g/L)groups.Baseline clinical data and thyroid function parameters[free triiodothyronine(FT3),free thyroxine(FT4),thyroid-stimulating hormone(TSH),TRAb,thyroglobulin antibodies(TgAb),thyroid peroxidase autoantibodies(TPOAb)]were collected.Systemic autoantibodies[antinuclear antibody(ANA)and extractable nuclear antigen(ENA)antibody profiles]were also assessed.Patients were followed at 1,3,6,9,12,and 24 months after treatment to evaluate thyroid function and antibody changes.After 3 years,discontinuation and relapse rates were obtained via telephone follow-up.Results:Among 159 included patients,26 were IgG4-positive and 133 were IgG4-negative.IgG4-positive patients had significantly higher serum IgG4 levels and a higher proportion of males(both P<0.05).Compared with the IgG4-negative group,IgG4-positive patients showed elevated FT3,TPOAb,TGAb,and globulin levels,with a lower albumin-toglobulin ratio(all P<0.05);ANA positivity at titers of 1:80,1:160,1:320,1:1000,and positivity for anti-SM,anti-SSA,and anti-UM-RNP antibodies were also higher(all P<0.05).No differences were found in age of onset,FT4,TSH,or TRAb(all P>0.05).Followup of 24 IgG4-positive and 93 IgG4-negative patients showed that at 12 months,TPOAb and TGAb remained higher in IgG4-positive patients,while at 24 months FT3 and FT4 were higher(all P<0.05).After 3 years,the discontinuation rate was lower in the IgG4-positive group(47.62%vs 71.26%,P=0.039)and relapse rate was higher(28.57%vs 14.94%),though the latter was not statistically significant(P=0.249).Conclusion:GD patients with elevated IgG4 levels are more frequently male,with higher FT3 and thyroid autoantibody levels and a more active systemic autoimmune profile.This subgroup has a lower treatment discontinuation rate and a higher relapse tendency,suggesting a more protracted disease course and poorer prognosis.Strengthened clinical recognition,long-term follow-up,and individualized treatment strategies are recommended,with attention to potential multisystem immune abnormalities.
作者
付怡雯
覃恬恬
赵少俐
何红晖
金萍
FU Yiwen;QIN Tiantian;ZHAO Shaoli;HE Honghui;JIN Ping(Department of Endocrinology,Third Xiangya Hospital,Central South University,Changsha 410013,China)
出处
《临床与病理杂志》
2025年第6期673-679,共7页
Journal of Clinical and Pathological Research
基金
湖南省自然科学基金(2024JJ9052)。
