细胞因子变化是否与IgA血管炎患儿肾损害相关？

背景IgA血管炎（IgAV）的长期预后取决于肾脏损伤的程度,有关IgAV肾损害发病机制的研究发现细胞因子在介导、驱动肾脏的损伤过程中发挥了重要作用。目的通过研究IgAV及肾损害患儿血清细胞因子水平变化,探讨细胞因子在IgAV肾损害过程中的意义和价值。方法选取2018年1月至2020年6月于中国医科大学附属盛京医院小儿肾脏内科住院的IgAV患儿194例作为研究对象,根据有无肾脏损害分为IgAV肾损害组（n=97）,IgAV组（n=97）,选取同时期本院儿童保健科进行体检的健康儿童60例为对照组。收集受试儿童及患儿细胞因子〔白介素（IL）-2、IL-4、IL-6、IL-10、IL-17、干扰素γ（IFN-γ）及肿瘤坏死因子α（TNF-α）〕以及患儿淋巴细胞绝对计数、免疫球蛋白A、免疫球蛋白E。采用多因素Logistic回归分析探讨IgAV肾损害的影响因素,绘制细胞因子对IgAV肾损害诊断价值的受试者工作特征（ROC）曲线。结果lgAV组IL-2水平高于lgAV肾损害组、对照组,且lgAV肾损害组IL-2水平高于对照组（P<0.05）;lgAV肾损害组IL-17水平高于lgAV组、对照组,lgAV组IL-17水平高于对照组（P<0.05）;lgAV组IL-6、IL-10和TNF-α水平高于lgAV肾损害组和对照组（P<0.05）;lgAV肾损害组和对照组IFN-γ水平高于lgAV组（P<0.05）。多因素Logistic回归分析结果显示,IL-2、IL-17、IFN-γ、TNF-α是IgAV肾损害发生的影响因素（P<0.05）。IL-2预测IgAV肾损害的ROC曲线下面积（AUC）为0.589,灵敏度为38.0%,特异度为47.0%;IL-17预测IgAV肾损害的AUC为0.621,灵敏度为47.4%,特异度为77.3%;IFN-γ预测IgAV肾损害的AUC为0.688,灵敏度为75.0%,特异度为55.7%;TNF-α预测IgAV肾损害的AUC为0.614,灵敏度为42.0%,特异度为37.0%;IL-17和IFN-γ联合预测IgAV肾损害的AUC为0.710,灵敏度为71.1%,特异度为66.0%。结论细胞因子IL-17、IFN-γ与IgAV肾损害的发生密切相关,早期检测两者水平并动态监测其变化,可对肾脏受累的早期发现及调整治疗方案起到预警作用。     

中枢神经系统血管炎与头痛

累及中枢神经系统的血管炎被称为中枢神经系统血管炎。头痛是中枢神经系统血管炎 的非特异表现之一,也是其中最常见的神经系统症状。目前按照2012年Chapel Hill会议（Chapel Hill consensus conference,CHCC）血管炎分类标准将血管炎按照受累血管大小不同进行分类。血管炎所致头 痛的发病机制不明,血脑屏障及神经血管单元的破坏在血管炎头痛中可能起到重要作用。不同类型 血管炎累及中枢神经系统的发生率以及头痛的发生时机和特点有差异。识别血管炎相关的头痛,并快 速进行诊断至关重要,以免进行不必要的治疗或导致严重神经系统后遗症。     

中性粒细胞胞外诱捕网与炎性疾病的研究进展

目的探讨中性粒细胞胞外诱捕网(NETs)对炎性疾病的调控机制,旨在为相关炎性疾病的治疗提供指导。方法复习近年来国内外有关NETs和炎性疾病之间关系的相关文献并加以综述。结果 NETs在脓毒症、抗中性粒细胞胞浆抗体(ANCA)相关性血管炎、急性胰腺炎、炎症性肠病等炎性疾病中发挥着重要作用,与疾病发生、发展或活动性有关。通过调控NETs形成通路,降低NETs的产生,能最终减轻疾病的炎症病情。结论 NETs参与了脓毒症、ANCA相关性血管炎、急性胰腺炎、炎症性肠病等炎性疾病的病程,但其调控机制仍有待更深入的探究及临床验证。     

Cerebral arteriostenosis associated with elevated serum-immunoglobulin E level in young adults without risk factors for ischemic stroke: A possible manifestation of cerebral vasculitis?

We report a series of young adults with symptomatic cerebral arteriostenosis characterized by elevated serum immunoglobulin (Ig) E levels. All patients had no definite risk factors for cerebral vascular diseases. The clinical data of 26 young adults (age 18–50 years) with ischemic stroke, characterized only by increased serum IgE levels and without risk factors for cerebral vascular disease, were retrospectively reviewed. Arteriostenosis was surveyed and followed-up by digital subtraction angiography (DSA), and the stenosis rate was estimated using the warfarin–aspirin symptomatic intracranial disease technique. All patients were treated with corticosteroids according to the common strategy for vasculitis. There was no recurrent stroke during follow-up. The mean degree of stenosis before and after treatment was 69.3 ± 29.8% and 47.9 ± 45.1%, respectively. The difference of stenosis rates between initial and follow-up DSA evaluation was significant using a paired samples test (21.31 ± 26.88, 95% confidence interval [CI] 13.58–29.03, t = 5.55, p < 0.001). Kaplan–Meier survival analysis revealed that the 13-month cumulative improved lesion rate was 40.3 ± 8.7%. This remained the same at 18 months. The mean time to lesion improvement was 12.58 ± 0.96 months (95% CI 10.70–14.46) and median time was 13 ± 3.88 months (95% CI 5.39–20.61). To our knowledge, cerebral arteriostenosis with only elevated IgE serum levels has not been reported. Our data showed that corticosteroid treatment can achieve clinical and artery improvement. This suggests that the cerebral arteriostenosis seen in our study might be caused by some specific type of vessel inflammation.     

大血管血管炎发病机制中的遗传因素

大血管血管炎包括大动脉炎和巨细胞动脉炎,病因涉及遗传、感染、环境、免疫反应等因素,发病机制仍待明确。在遗传背景研究方面发现,大动脉炎与HLA-Ⅰ类基因区(HLA-B*52)关系最为密切,参与炎症反应的相关基因(IL12B、IL6、RPS9/LILRB3)也发挥着重要作用。在巨细胞动脉炎中,HLA-Ⅱ类(HLA-DRB1*04、HLA-DQA1)基因区发挥着主要作用,PTPN22等非HLA基因也与巨细胞动脉炎的发病相关。     

Positive classic antineutrophil cytoplasmic antibody (C‐ANCA) titer at switch to azathioprine therapy associated with relapse in proteinase 3–related vasculitis

Objective

To analyze disease‐free survival in patients with antineutrophil cytoplasmic antibody (ANCA)–associated small‐vessel vasculitis (AAV) treated with cyclophosphamide only or switched to azathioprine after 3 months of full remission while taking cyclophosphamide.

Methods

We analyzed disease‐free survival in all consecutive patients diagnosed with AAV between 1990 and 2000 at our center. Patients were treated with cyclophosphamide only (1990–1996) or switched to azathioprine after 3 months of remission while taking cyclophosphamide (1997–2000). All patients received at least 12 months of followup.

Results

Of the total 128 patients, 53 (41%) relapsed. Forty‐four of the 128 patients (34%) had been switched to azathioprine therapy. Disease‐free survival at 2 and 4 years was 76% and 65% in the cyclophosphamide group compared with 76% and 51% in the azathioprine group. In patients with proteinase 3 (PR3) classic ANCA (C‐ANCA)–associated vasculitis who were switched to azathioprine (n = 33), a positive C‐ANCA titer at the moment of treatment switch (n = 13) was significantly associated with relapse (RR 2.6, 95% confidence interval 1.1–8.0; P = 0.04). In patients with a negative ANCA titer at the time of switch to azathioprine, disease‐free survival at 2 and 4 years was 80% and 62%, which was identical to that for patients treated with cyclophosphamide only. In patients who were ANCA‐positive at the time of treatment switch, disease‐free survival at 2 and 4 years was only 58% and 17%.

Conclusion

Switching cyclophosphamide to azathioprine after induction of remission in patients with PR3‐ANCA‐associated vasculitis who are still ANCA‐positive at the time of treatment switch is associated with a high risk of relapse.

     

Henoch-Schönlein purpura in a patient with oesophageal cancer: A case report

Rationale:Understanding the association between Henoch-Schönlein purpura (HSP) and malignancy is essential for early diagnosis and treatment of the potential lethal disease. To the best of our knowledge, there has been only one published case of HSP coexisting with oesophageal cancer. Here, we report another patient diagnosed with HSP and oesophageal squamous carcinoma simultaneously.Patient concerns:A 60-year-old Chinese male was referred to our hospital because of intermittent abdominal pain, abdominal distension, melena, lower extremities purpura. Positive laboratory values included pancytopenia, microscopic hematuria, nephrotic proteinuria, hematochezia, hypoalbuminemia, hyperlipidaemia, hypocomplementemia, and increased levels of hepatobiliary enzymes and immunoglobulin (Ig) A. Gastrocolonoscopy showed multiple erosion lesion on descending duodenum, terminal ileum, and ileal flap. Biopsy of these lesions suggested non-specific inflammation.Diagnoses:HSP (IIIb type) was diagnosed based on renal pathology examination in accordance with the International Study of Kidney Disease in Children (ISKDC) classification. Liver biopsy confirmed the diagnosis of nodular cirrhosis (Ishak 5). Gastroscopy unintentionally revealed three oesophagus lesions. Pathology study suggested intermediate differentiated squamous cell carcinoma (cTNM IB).Interventions:Before admission, he was administered intravenous Ig 10 g once daily(qd) for 10 days, methylprednisolone 40 mg qd for a week, followed by prednisolone 50 mg qd for almost 8 weeks. Endoscopic submucosal dissection (ESD) was performed to remove all lesions with negative margin after prednisolone was tapered (5 mg per week until 10 mg qd).Outcomes:Despite prednisone being tapered to 2.5 mg qd within 2 months, complete remission of HSP and esophageal malignancy was achieved after the resection of the esophagus lesions during 12 months follow-up.Lessons:We report a rare case of oesophageal squamous cell carcinoma initially presented as HSP. This case suggests the importance of evaluating adult patients with HSP for an underlying malignancy.     

Vascularites double-positives ANCA et anti-MBG : mise au point sur les spécificités cliniques et thérapeutiques et comparaison aux deux vascularites éponymes

Double-positive vasculitis with anti-polynuclear cytoplasm (ANCA) and anti-glomerular basement membrane (GBM) antibodies is a rare entity of systemic vasculitis defined by the presence of ANCA and anti-GBM antibodies. The gradual accumulation of clinical and therapeutic data shows the usefulness of identifying and differentiating this entity from the two vasculitis respectively associated with the isolated presence of each of these two antibodies. Indeed, the double-positive ANCA and anti-GBM vasculitis appears to associate the characteristics of the demography and the extra-renal and pulmonary involvement of the ANCA-associated vasculitis on the one hand, and of the histological type and severe renal prognosis of the anti-MBG vasculitis on the other hand, with the renal involvement which is the only involvement consistently observed in double-positive vasculitis. The aim of this focus is to describe the epidemiological, clinico-biological, histological and prognostic characteristics of this entity, in light of recent literature and ongoing therapeutic changes in the two eponymous vasculitis.