Matsushita Tomonori, Tachibana Mitsuhiro, Nakagawa Hiromichi, Goto Shuhei, Nishizawa Koji, Kobayashi Takashi, Fukuzawa Shigeki, Itoh Kunihiko
Department of Urology, Shimada General Medical Center, Shimada, Shizuoka, Japan.
Department of Urology, Kyoto University Hospital, Kyoto, Kyoto, Japan.
Front Immunol. 2025 Jul 10;16:1591847. doi: 10.3389/fimmu.2025.1591847. eCollection 2025.
Idiopathic retroperitoneal fibrosis is an IgG4-related disease where pathological role and clinical significance of IgG4 antibodies remain largely unknown. This report shows a rare case of retroperitoneal fibrosis in presence of Autoimmune coagulation factor XIII deficiency, in which an acute life-threatening hemorrhage was successfully managed with effective treatment strategies. Following this, we investigated the molecular mechanisms underlying the patient's pathology using experimental translational approach.
The patient was a 60-year-old Asian man with a retroperitoneal mass. A laparoscopic biopsy confirmed that the lesion was retroperitoneal fibrosis with IgG4-expressing plasma cell infiltration. Though biopsy was completed without complications, the patient experienced repeated life-threatening intraperitoneal bleeding starting the next day. Despite performing one emergency laparotomy and three series of emergency transcatheter arterial embolization along with massive transfusions, achieving hemostasis was difficult. Suspecting a humoral autoimmune hemorrhagic disorder, we performed plasma exchange, which achieved complete hemostasis. Later, an abnormal decrease in the activity of coagulation Factor XIII was observed, leading to the diagnosis of Autoimmune coagulation Factor XIII deficiency. Subsequent treatment with steroids and coagulation Factor XIII concentrates prevented further bleeding. We investigated the potential involvement of IgG4-related disease and the effects of IgG4 on coagulation Factor XIII using an system, and it was demonstrated that both IgG1 and IgG4 recognized the A subunit of coagulation Factor XIII. The purified IgG antibody samples containing IgG1 and IgG4 were shown to significantly reduce the function of coagulation Factor XIII derived from healthy individuals.
The patient experienced recurrent life-threatening bleeding due to Autoimmune coagulation Factor XIII deficiency, which was successfully controlled through plasma exchange therapy. This is the first reported case of concurrent retroperitoneal fibrosis and Autoimmune coagulation Factor XIII deficiency. Based on the results of our research, it is suggested IgG4 may play a role in the pathology of both disorders. It was hypothesized that this hematological disorder could be a part of the spectrum of IgG4 autoimmune diseases.
特发性腹膜后纤维化是一种IgG4相关疾病，其中IgG4抗体的病理作用和临床意义在很大程度上仍不清楚。本报告展示了一例罕见的伴有自身免疫性凝血因子XIII缺乏的腹膜后纤维化病例，其中通过有效的治疗策略成功处理了危及生命的急性出血。在此之后，我们采用实验性转化方法研究了该患者病理背后的分子机制。
该患者是一名60岁的亚洲男性，患有腹膜后肿块。腹腔镜活检证实病变为伴有IgG4表达浆细胞浸润的腹膜后纤维化。尽管活检完成时没有并发症，但患者从第二天开始反复出现危及生命的腹腔内出血。尽管进行了一次急诊剖腹手术、三轮急诊经导管动脉栓塞以及大量输血，但止血困难。怀疑是体液性自身免疫性出血性疾病，我们进行了血浆置换，实现了完全止血。后来，观察到凝血因子XIII活性异常降低，从而诊断为自身免疫性凝血因子XIII缺乏。随后使用类固醇和凝血因子XIII浓缩物进行治疗防止了进一步出血。我们使用一个系统研究了IgG4相关疾病的潜在参与情况以及IgG4对凝血因子XIII的影响，结果表明IgG1和IgG4都识别凝血因子XIII的A亚基。含有IgG1和IgG4的纯化IgG抗体样本显示能显著降低健康个体来源的凝血因子XIII的功能。
该患者因自身免疫性凝血因子XIII缺乏经历了反复的危及生命的出血，通过血浆置换疗法成功得到控制。这是首例同时并发腹膜后纤维化和自身免疫性凝血因子XIII缺乏的报告病例。基于我们的研究结果，提示IgG4可能在这两种疾病的病理过程中起作用。据推测，这种血液系统疾病可能是IgG4自身免疫性疾病谱的一部分。
