过敏性紫癜肾炎患儿血清IgA1半乳糖水平的测定

目的了解过敏性紫癜肾炎患儿血清IgA1半乳糖水平。方法研究对象分成三组,分别为过敏性紫癜肾炎组（n=20）,非IgA肾病、过敏性紫癜肾炎组（n=18）,正常对照组（n=18）。用蚕豆凝集素（vicia villosa lectin,VVL）亲和ELISA法测定IgA1与VVL的结合力,间接反映IgA1的半乳糖水平,结合力高提示IgA1半乳糖水平低。结果过敏性紫癜肾炎组患儿血清IgA1分子与VVL结合力[（0.34±0.09）U]高于正常对照组[（0.27±0.06）U]及非IgA肾病、过敏性紫癜肾炎组[（0.28±0.08）U]（P〈0.05）。结论过敏性紫癜肾炎患儿血清IgA1呈低半乳糖基化。     

IgA nephropathy associated with Crohn's disease

The relationship between IgA nephropathy (IgAN) and Crohn’s disease was reported. IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure, and up to 50% of cases progressed to end-stage renal disease within 25 years after IgAN diagnosis. However, specific and effective therapeutic strategies are still lacking. In this review, we discuss the possibility of the mechanism involved in IgAN associated with Crohn’s disease based on the findings of basic and clinical studies. Although the etiology of IgAN associated with Crohn’s disease is not permanent and various factors are thought to be involved, the stabilization of the disease condition of Crohn’s disease is believed to help treat IgAN.     

Celiac disease: epidemiology, pathogenesis, diagnosis, and nutritional management.

Celiac disease (CD) is an inflammatory small intestinal disorder that can lead to severe villous atrophy, malabsorption, and malignancy. It is triggered by the gluten proteins of wheat, barley, and rye. All patients express the antigen-presenting molecules human leukocyte antigen-DQ2 (HLA-DQ2) and/or HLA-DQ8, which bind gluten peptides and thus activate destructive intestinal T cells. Patients with untreated CD have circulating IgA autoantibodies to the enzyme tissue transglutaminase (tTG), a component of endomysium. Testing for serum IgA tTG has a high predictive value. Therapy of CD is a lifelong gluten-free diet. Counseling by an expert dietitian and association with a celiac support group are important in helping the patient embark on a healthy gluten-free diet. Current research focuses on non-dietary therapies and treatment of refractory (diet-unresponsive) CD.     

过敏性紫癜肾炎患儿血清IgA1半乳糖水平的测定

目的了解过敏性紫癜肾炎患儿血清IgA1半乳糖水平。方法研究对象分成三组,分别为过敏性紫癜肾炎组(n=20),非IgA肾病、过敏性紫癜肾炎组(n=18),正常对照组(n=18)。用蚕豆凝集素(vicia villosa lectin,VVL)亲和ELISA法测定IgA1与VVL的结合力,间接反映IgA1的半乳糖水平,结合力高提示IgA1半乳糖水平低。结果过敏性紫癜肾炎组患儿血清IgA1分子与VVL结合力[(0.34±0.09)U]高于正常对照组[(0.27±0.06)U]及非IgA肾病、过敏性紫癜肾炎组[(0.28±0.08)U](P<0.05)。结论过敏性紫癜肾炎患儿血清IgA1呈低半乳糖基化。     

Clinical inquiries: What blood tests help diagnose celiac disease?

Histological confirmation of infiltrative lesions via small bowel biopsy is the gold standard for diagnosing celiac disease. Four serum antibody assays may serve as a first-step diagnostic tool to identify biopsy candidates: immunoglobulin A tissue transglutaminase (IgA tTG), IgA endomysial antibody (IgA EMA), IgA antigliadin antibody (IgA AGA), and IgG antigliadin antibody (IgG AGA). IgA tTG and IgA EMA offer the best diagnostic accuracy. Patients with selective IgA deficiency may have falsely negative IgA assays (strength of recommendation [SOR]: B, based on a systematic review, multiple small cross-sectional studies, and expert opinion).     

Screening for celiac disease in short bowel syndrome.

BACKGROUND: Malabsorptive diarrhea due to short bowel syndrome (SBS) results in nutrition compromise, often requiring parenteral nutrition (PN). Activation of latent celiac disease can occur after gastrointestinal surgery. Our objective was to determine whether undiagnosed celiac disease contributes to malabsorption in patients with SBS. METHODS: Adult subjects with SBS were tested for celiac disease using immunoglobulin A (IgA) tissue transglutaminase (TTG) antibody and total IgA level. Subjects with an elevated IgA tissue transglutaminase were offered upper endoscopy with biopsies of the duodenum. RESULTS: Eighteen subjects were enrolled. The subjects were predominantly white, and the most common cause of SBS was Crohn's disease. The mean length of remaining small bowel was 93.1 +/- 54.6 cm. All subjects had undergone surgeries, resulting in loss of the ileocecal valve. Five subjects were found to have an elevated total IgA. A single patient was found to have an elevated IgA tissue transglutaminase antibody, and subsequent endoscopy demonstrated active gastroduodenal Crohn's disease, without features of celiac disease. CONCLUSIONS: No subjects were IgA deficient, but 5 subjects were found to have elevated IgA levels. Undiagnosed celiac disease did not contribute to malabsorption in our small cohort of predominantly white SBS patients. Larger studies are warranted.     

PAI-1在IgA肾病小鼠肾组织中表达的变化及益肾汤对其的影响

目的探讨IgA肾病（IgAN）小鼠肾组织Ⅰ型纤溶酶原激活物抑制因子（PAI-1）含量及其mRNA表达的特点及益肾汤对其的影响。方法用“口服牛血清白蛋白联合尾静脉注射葡萄球菌肠毒素B”法复制小鼠IgAN模型。设正常组、模型组、益肾汤高浓度治疗组和益肾汤低浓度治疗组。FQ-PCR法检测小鼠肾组织PAl-1mRNA表达、免疫组化SABC法检测小鼠肾组织PAI-1的含量。结果模型组小鼠肾组织PAl-1含量及其mRNA表达显著高于正常组（P〈0．05）；益肾汤低浓度及高浓度组小鼠肾组织PAl-1含量及其mRNA表达分别与模型组比较差异均有统计学意义（P〈0.05）；益肾汤低浓度及高浓度组之间PAI-1含量及其mRNA表达差异无统计学意义（P〉0．05）。结论IgAN肾组织PAl-1含量及mRNA的表达均明显增加；益肾汤可显著减少IgAN小鼠肾组织中PAI-1的含量及抑制其mRNA表达。     

尿足细胞阳性IgA肾病患者临床病理特点

目的探讨尿足细胞阳性原发性IgA肾病（IgAN）患者临床病理特点。方法50例肾活检明确诊断的IgAN患者和10例健康志愿者,利用足细胞的标记蛋白Podocalyxin（PCX）标记尿液和肾组织足细胞,采集IgAN患者肾活检时临床资料、肾活检光镜结果,其中光镜参照Hass分级,各项病理指标参照Fofi半定量积分法进行评分,荧光显微镜观察肾组织足细胞PCX荧光表达程度,电镜观察足细胞足突形态学改变。结果①尿足细胞阳性的IgAN患者尿蛋白水平、血肌酐水平、平均动脉压较尿足细胞阴性患者增高,血浆白蛋白、肾小球滤过率（GFR）较尿足细胞阴性患者降低（P〈0．05）;②光镜示尿足细胞阳性的IgAN患者肾小球硬化程度、新月体发生率较尿足细胞阴性患者增高（P〈0．05）,而两组比较,系膜增生、基质增多、肾小管萎缩、间质纤维化、间质炎细胞浸润、间质血管硬化程度的差异无统计学意义（P〉0．05）;③肾组织足细胞PCX抗体荧光表达显示：肾小球节段硬化和球性硬化处足细胞PCX抗体荧光表达缺失;④电镜观察提示,无论是否伴足细胞尿,其足细胞足突均可出现一系列形态学改变。结论足细胞尿是反映肾脏疾病轻重的一个指标,与肾脏病理类型有一定关系。     

Mortality Excess in Individuals with Elevated IgA Anti-Transglutaminase Antibodies: The KORA/MONICA Augsburg Cohort Study 1989–1998

Objectives : Immunoglobulin A (IgA) autoantibodies to tissue transglutaminase (tTG) are commonly used for screening and diagnosing of celiac disease. We examined the hypothesis that elevated IgA anti-tTG antibodies were associated with higher all-cause mortality risk. Methods The cohort, 2333 men and 2300 women, was based on the follow-up of participants of a representative population-based survey in Southern Germany (KORA/MONICA Augsburg project) conducted in 1989–1990. The endpoint for the vital status with cause of death was the year 1998. The sera drawn at baseline and stored at −80 °C, were recently screened with an IgA enzyme-linked immunosorbent assay (ELISA) using human recombinant tTG. Age-standardized mortality rates and age-adjusted hazard ratios were calculated. Results From the 4633 sera analyzed, 63 had an IgA anti-tTG concentration ≥7 AU/ml. Of these 63 individuals, 15 died between 1989 and 1998. The age-adjusted hazard ratio (HR_a) of all-cause mortality was 1.86 (95% CI: 1.01–3.41) and 3.92 (95% CI: 1.44–10.71) for men and women, respectively. The excess of cancer mortality was even higher with an HR_a of 2.47 (95% CI: 0.89–6.83) in men and of 6.65 (95% CI: 2.04–21.63) in women. Conclusions: Individuals with elevated IgA anti-tTG antibodies had a highly increased mortality risk, particularly due to cancer. New studies are necessary to clarify if this increased risk is due to undiagnosed celiac disease or/and if this elevated IgA anti-tTG antibodies level is a marker of serious diseases like cancer, chronic liver disease or end-stage heart failure.     

肾血管病变在IgA肾病病理中的意义

目的 探讨肾血管病变与肾小球病理改变之间的关系。方法 回顾性分析肾活检病例1833例,其中IgA肾病1093例,非IgA肾病740例。采用方差检验对各组资料进行统计分析。结果在1093例IgA肾病中有肾血管病变者426例,占39％,在740例非IgA肾病中存在肾血管病变者为182例占25％,两者有显著性差异（P〈0．01）。在IgA肾病的肾血管病变中,主要是以肾小动脉内膜增厚、纤维化及管腔狭窄病变为主。IgA肾病各亚型中存在肾血管病变的分布为：轻微病变型22．5％（36／160）,局灶节段增生型41％（195／476）,系膜增生型39．1％（135／345）,硬化型93．1（27／29）。此分布的不同具有显著性差异（P〈0．01）。结论IgA肾病通常会伴有多种肾间质血管病变,并且血管病变与IgA肾病的病理改变及临床特点密切相关,提示肾血管病变是影响IgA肾病发展的重要因素。     

IgA肾病患者血清聚合IgA1对足细胞增殖的影响

目的观察IgA肾病（IgA nephropathy,IgAN）患者与正常人的血清热聚合IgAl（aggregated IgAl,aIgAl）对足细胞增殖的影响。方法收集原发性IgAN患者及健康人的血清,利用层析法分离获得血清单体IgAl（monomefic IgAl,mIgAl）,将mIgA1热聚合为aIgA1。利用浓度为0．25、0．5、1．2m咖l的患者与正常人的algA1分别刺激小鼠MPC5足细胞株,利用MTT法检测algA1对足细胞增殖的影响。结果正常组和患者组aIgA1刺激足细胞后细胞MTT吸光度的差异无统计学意义。刺激24h组与刺激48h组MTT吸光度的差异也无统计学意义。不同浓度aIgA1刺激组间MTT吸光度的差异有统计学意义P〈0．05）,相比于不加刺激的阴性对照组（SFM）,1、2mg／ml组的吸光度分别为其0．46和1．66倍。结论足细胞可能会直接对IgA1产生反应,algA1可以影响足细胞增殖;低浓度aIgA1抑制足细胞增殖,高浓度algA1促进足细胞增殖;患者与正常人的aIgA1对足细胞增殖的影响没有不同。     

Dietary fish oil suppresses experimental immunoglobulin a nephropathy in mice

Dietary fish oil (FO) supplementation reportedly retards the progression of renal disease in patients with immunoglobulin (Ig)A nephropathy (IgAN), the most common glomerulonephritis worldwide. Using an experimental mouse model in which early immunopathological hallmarks of IgAN are induced by the mycotoxin vomitoxin (VT), the ameliorative effects of FO ingestion on this disease were evaluated in two studies. In Study 1, the capacity of VT to induce IgAN was evaluated in mice fed for 12 wk AIN-76A diets containing 50 g/kg corn oil (CO), 50 g/kg CO plus 9 mg/kg tert butylhydroquinone (TBHQ), or 5 g/kg CO plus 45 g/kg menhaden FO that contained 200 mg/kg TBHQ. Serum IgA, serum IgA immune complexes and kidney mesangial IgA deposition were greater in mice fed VT + CO compared with the CO control group, whereas all three variables were significantly attenuated in mice fed VT + FO. Although TBHQ also had attenuating effects, these were significantly less than those for the VT + FO group. In Study 2, the effects of feeding modified AIN 93G diets containing either 70 g/kg CO or 10 g/kg CO plus 60 g/kg FO for 20 wk on VT-induced IgAN were compared. Again, consumption of FO attenuated all three immunopathological variables. In addition, spleen cell cultures from the VT + FO group produced markedly less IgA than those cultures from mice fed VT + CO. Taken together, the results suggested that diets containing FO may impair early immunopathogenesis in VT-induced IgAN and that this was not totally dependent on the presence of the antioxidant TBHQ.     

血管内皮生长因子及其受体与IgA肾病

IgA肾病血管内皮生长因子及其受体(VEGF/VEGFR)在肾脏组织局部、血浆及尿液中的含量发生变化.VEGF/VEGFR通过改变内皮细胞的结构和功能、增加肾小球毛细血管通透性、诱导细胞外基质合成、血管生成障碍等机理参与IgA肾病的发生与进展.     

186例成人IgA肾病临床病理分析

目的研究成人IgA肾病(IgAN)的临床、病理特点及相关性. 方法将我科于1996年8月～2003年12月收治的原发性成人IgAN186例按照年龄分成2组,根据各年龄组的临床及其组织学特点进行临床与病理分型的分析. 结果 186例成人IgAN临床表现以无症状性尿检异常最常见,占122例(65.6%),其次是慢性肾炎和肾病综合征,分别占28例(15.1%)和25例(13.4%).老年组肾病综合征和急性肾功能衰竭的发生率高于青壮年组.病理类型以局灶节段硬化性肾小球肾炎最常见,占67例(36%),其次是系膜增生性肾小球肾炎、轻微病变肾小球肾炎,分别为47例(25.3%)和35例(18.8%). 结论成人IgAN的临床病理表现多样化并且有一定特点.临床表现以无症状性尿检异常最常见,病理类型以局灶节段性肾小球病变最常见.     

IgA肾病孕妇的临床资料分析

目的 分析浙江中医药大学附属温州中医院近10年IgA肾病孕妇的妊娠结局及其危险因素.方法 选取我院2006年6月至2016年8月收治的IgA肾病孕妇86例的临床资料,分析其妊娠结局的影响因素.结果 86例患者共妊娠90次,妊娠20 ～ 40周,平均(36.2±5.6)周.58例为足月产,9例为早产,23例于妊娠28周前终止妊娠,分别占64.44％、10.00％和25.56％.67例胎儿中62例活胎,体重1 038.9～5 896.3 g,平均体重为(3 012.5 ±253.9)g;低体重儿14例,极低体重儿6例,分别占22.58％和9.67％.妊娠成功组年龄、平均动脉压、血肌酐、妊娠前24h尿蛋白量显著低于失败组(t值分别为2.332、2.257、2.259、2.225,均P＜0.05),血红蛋白显著高于失败组(t=2.302,P＜0.05),Lee氏分级显著低于失败组(x2=5.661,P＜0.05).两组病程、血清白蛋白、总胆固醇无显著性差异(t值分别为1.025、0.562、0.785,均P＞0.05),且肾小球球性硬化、肾小球节段性硬化发生率均无显著性差异(x2值分别为1.535、0.981,均P＞0.05).Logistic回归分析结果显示,年龄、妊娠前肾性高血压、Lee氏分级、血红蛋白和妊娠前24h尿蛋白量是IgA肾病孕妇妊娠结局的独立影响因素(OR值分别为3.038、3.927、3.358、2.038,均P ＜0.05),年龄越大,Lee氏分级越高,妊娠前24h尿蛋白量高,低血红蛋白,伴有妊娠前肾性高血压的IgA肾病孕妇更易出现不良妊娠结局,胎儿预后亦差.结论 IgA肾病可能导致妊娠结局不良,其中妊娠前肾病的临床表现与妊娠结局存在紧密关系,应积极控制妊娠前上述症状,从而改善妊娠结局.     

Prospective study of clinical and histological safety of pure and uncontaminated Canadian oats in the management of celiac disease

Background: Pure oats are safe for most patients with celiac disease, but concerns regarding contamination by other grains limit their consumption. The Canadian Celiac Association recently released guidelines governing the production of pure oats. The objective was to test the safety of a product manufactured under these guidelines. Methods: Fifteen adults with established, biopsy‐confirmed celiac disease of ≥1 year duration were challenged with 350 g/wk of pure oats for 12 weeks. Symptom scores, weight, hemoglobin, ferritin, albumin, and tissue transglutaminase (tTG) were assessed at weeks 0, 6, and 12. Duodenal biopsies were obtained before and after oat challenge and assessed based on the modified Marsh–Oberhuber score. Compliance with a gluten‐free diet was monitored with random food diaries. Results: Fifteen patients completed the study and were analyzed in intention‐to‐treat and per‐protocol analyses. There were no significant changes in symptom scores, weight, hemoglobin, ferritin, or albumin during oat consumption. The tTG remained negative in all patients, and the histology scores did not significantly change during oat challenge. The only relapse occurred in a patient who became noncompliant with her gluten‐free diet. Conclusion: The findings support the safety of pure, uncontaminated oats manufactured under Canadian Celiac Association guidelines for patients with celiac disease.     

小儿IgA肾病临床病理分析

目的:探讨小儿IgA肾病(IgAN)临床病理特点。方法:对我院1984～2005年6月经皮肾活检病理检查确诊的小儿原发性IgA肾病的临床病理资料进行回顾性分析。结果:小儿IgAN临床以单纯血尿最常见(36.8%),其次是血尿伴蛋白尿(31.6%);临床表现及病理改变以肾病综合征最重,其次是血尿伴蛋白尿,易合并肾功能不全和高血压;肾病综合征的免疫复合物沉积以IgA+IgG+IgM型多见,单纯血尿、血尿伴蛋白尿以IgA+IgG型免疫复合物沉积为主。结论:小儿IgAN的临床及病理分级与治疗及其预后有关,只有通过肾活检病理检查才能更好地认识小儿IgAN,制定正确的治疗方案,客观的评估预后。     

53例IgA肾病临床相关研究

目的：分析血清IgA对IgA肾病（IgAN）发生发展的影响,探讨影响kAN预后的病理和临床因素。方法：分析53例IgAN患者血清IgA以及Katafuchi积分、24小时尿蛋白、年龄及高血压等对IgAN发生发展及预后的影响。结果：①IgAN组血清IgA明显高于非IgAN组及对照组,病理损害较重的Ⅳ-V级组血清IgA明显高于病理损害较轻的I-Ⅲ级组;②与病理损害较轻的I-Ⅲ级组相比,病理损害较重的Ⅳ-V级组Katafuchi积分、24小时尿蛋白、年龄及高血压均明显增高。结论：IgAN是一种免疫复合物性肾小球肾炎,血清IgA的升高对IgAN的诊断及判断病情严重程度有一定的意义。Katafuchi积分能较满意地判断IgAN的病情严重程度。年龄、高血压、持续性蛋白尿是IgAN进展的危险因素．     

IgA肾病中关于细胞凋亡的研究进展

IgA肾病(IgAN)是全球范围内最常见的原发性肾小球疾病之一,近年来在儿童中的患病率明显升高,部分患儿最终发展为终末期肾病(ESRD),对儿童的生活质量及生命造成了严重威胁;由于其发病机理尚不明确,以及临床表现的多样性和预后的差异性,在临床上尚无疗效确切公认的治疗方法,药物治疗是常用的治疗手段.细胞凋亡是细胞生命活动中的基本现象,是近年生命科学研究的热点.该文对IgAN中有关细胞凋亡的研究进展进行综述,指出对细胞凋亡的干预可能是一种对IgAN新的治疗靶点.     

Demonstration of antibodies against gliadin using an immunofluorescence method in childhood celiac disease

IgA and IgG type antibodies against gliadin were demonstrated in 396 serum samples of 350 patients with immunofluorescence method. The procedure was used in cases of clinically suspected celiac disease and for the control of the diet of patients with diagnosed celiac disease. The sensitivity of the patient material was 83% in the case of antibodies against IgA and 85% with antibodies against IgG. The specificity value with IgA antibodies was 96% and 91% with IgG antibodies. The authors consider the immunofluorescence technique suitable for the demonstration of immune complexes developed against gliadin and circulating in blood. On this basis the method is recommended both for the screening test of patients with suspected celiac disease and for the control of patients on gluten-free diet.