IgG4相关疾病发病机制及治疗进展

Progress on the pathogenesis and treatment of IgG4-related disease

IgG4相关疾病是近20年才被广泛认识的一种自身免疫相关的纤维炎性疾病,它几乎可以累及全身任何部位,多发病于泪腺、唾液腺、胆道、胰腺、腹膜后组织等。其主要临床表现为累及部位的肿胀或占位,导致受累组织脏器的正常功能受损。如果未得到有效治疗,终末期纤维化会造成患者多个器官功能衰竭,极大地影响患者的生存质量。在过去,该病常被漏诊或误诊为炎症或肿瘤,近年来随着对其认识的深入及诊断水平的提高,临床确诊病例数逐渐增多,这些患者也在接受早期治疗后获益。目前,IgG4相关疾病的主要治疗方法包括药物控制和手术切除,其中药物治疗处于主导地位。虽然大部分患者使用激素或传统的改善病情抗风湿药物后能达到缓解,但仍存在一些难以诱导缓解、反复复发、有激素或其他药物使用禁忌的病例,这也是当前治疗IgG4相关疾病面临的主要难题。IgG4相关疾病发病机制的研究在近年来取得较大进展,这不仅使得研究者对该病的认识更加深入,同时为该病治疗提供了新的思路,利妥昔单抗就是其中的典型代表。本文总结归纳了IgG4相关疾病发病机制研究进展和针对该病的治疗药物及其治疗原理,并展望了具有发展潜力的治疗药物和药物开发方向,以期对该病进行更好的临床治疗与管理。

IgG4-related disease(IgG4-RD)is a newly recognized fibro-inflammatory condition of autoimmune etiology in recent twenty years,mainly manifesting as mass-forming lesions in single or multiple organs.In the past,it was often missed or misdiagnosed as inflammation or tumor.Patients may die from multiple organ failure due to end-stage fibrosis if they are not treated promptly.However,the number of clinically confirmed cases has gradually increased with the improvement of diagnostic level in recent years,and these patients have benefited greatly after receiving early treatment.Although patients generally respond well to traditional immunosuppressors including glucocorticoids and disease-modifying anti-rheumatic drugs,refractory and recurrent cases,even patients with glucocorticoid contraindication are common.Important mechanistic insights have been derived from studies of B-cell depletion therapy,but greater awareness of the pathophysiology of IgG4-RD is still badly needed to identify novel therapeutic targets.In this article,we reviewed the pathogenesis progress and promising therapy of IgG4-RD to seek better clinical management of IgG4-RD.