A monocenter retrospective study of serological,histological and genetic characteristics of celiac disease in Northern Central Italy

Objective: To examine the seroprevalence, correlates and characteristics of Celiac disease (CD) in a population sample of a Northern Central Area of Italy, by a monocenter retrospective study. Methods: Between 2006 and 2010, serum samples of 9371 subjects (age range 6 months to 91 years) were screened for tissue transglutaminase IgA antibodies (IgA-tTG) by the Immunologia-Allergologia Unit of AUSL1 Massa-Carrara, an area with a population of approximately 150,000. Endomysial IgA antibodies (EMA), HLA typing and small-bowel biopsy were also performed when indicated. Results: Of the 9371 subjects, 269 (2.87%) had positive antibody tests. The population was divided into several age groups and the highest prevalence (5.63%) was found in the 6 months-3 years group. The prevalence of IgA-tTG positivity was double in females compared to males. All IgA-tTG positive patients that were genotyped carried HLA-DQ2 or DQ8, none was a5 positive only. In positive IgA-tTG sera, levels of IgA-tTG were significantly higher in EMA positive than in EMA negative sera (p in children and in adults. Ninety-five/269 IgA-tTG positive subjects underwent biopsy. IgA-tTG levels were different according to the histological degree of the lesion. When EMA were evaluated in IgA-tTG positive subjects the number of EMA negative sera was significantly higher in adults than in children. Conclusions: In summary, this study provides a monocenter retrospective analysis of serological, histological and genetic parameters of subjects with suspicion of CD in an area of Northern Central Italy from 2006 to 2010.

Tissue transglutaminase levels above 100 U/mL and celiac disease:A prospective study

AIM:To investigate whether a tissue-transglutaminase antibody(tTGA) level ≥ 100 U/mL is sufficient for the diagnosis of celiac disease(CD).METHODS:Children suspected of having CD were prospectively included in our study between March 2009 and September 2011.All patients with immune globulin A deficiency and all patients on a gluten-free diet were excluded from the study.Anti-endomysium antibodies(EMA) were detected by means of immunofluorescence using sections of distal monkey esophagus(EUROIMMUN,Luebeck,Germany).Serum anti-tTGA were measured by means of enzyme-linked immunosorbent assay using human recombinant tissue transglutaminase(ELiA Celikey IgA kit Phadia AB,Uppsala,Sweden).The histological slides were graded by a single experienced pathologist using the Marsh classification as modified by Oberhuber.Marsh Ⅱ and Ⅲ lesions were considered to be diagnostic for the disease.The positive predictive values(PPVs),negative predictive values(NPVs),sensitivity and specificity of EMA and tTGA along with their 95% CI(for the cut off values > 10 and ≥ 100 U/mL) were calculated using histology as the gold standard for CD.RESULTS:A total of 183 children were included in the study.A total of 70(38.3%) were male,while 113(61.7%) were female.The age range was between 1.0 and 17.6 years,and the mean age was 6.2 years.One hundred twenty(65.6%) patients had a small intestinal biopsy diagnostic for the disease;3 patients had a Marsh Ⅱ lesion,and 117 patients had a Marsh Ⅲ lesion.Of the patients without CD,only 4 patients had a MarshⅠlesion.Of the 183 patients,136 patients were positive for EMA,of whom 20 did not have CD,yielding a PPV for EMA of 85%(95% CI:78%-90%) and a corresponding specificity of 68%(95% CI:55%-79%).The NPV and specificity for EMA were 91%(95% CI:79%-97%) and 97%(95% CI:91%-99%),respectively.Increased levels of tTGA were found in 130 patients,although only 116 patients truly had histological evidence of the disease.The PPV for tTGA was 89%(95% CI:82%-94%),and the corresponding specificity was 78%(95% CI:65%-87%).The NPV and sensitivity were 92%(95% CI:81%-98%) and 97%(95% CI:91%-99%),respectively.A tTGA level ≥ 100 U/mL was found in 87(47.5%) patients,all of whom were also positive for EMA.In all these 87 patients,epithelial lesions confirming CD were found,giving a PPV of 100%(95%CI:95%-100%).The corresponding specificity for this cutoff value was also 100%(95% CI:93%-100%).Within this group,a total of 83 patients had symptoms,at least gastrointestinal and/or growth retardation.Three patients were asymptomatic but were screened because they belonged to a group at risk for CD(diabetes mellitus type 1 or positive family history).The fourth patient who lacked CD-symptoms was detected by coincidence during an endoscopy performed for gastro-intestinal bleeding.CONCLUSION:This study confirms based on prospective data that a small intestinal biopsy is not necessary for the diagnosis of CD in symptomatic patients with tTGA ≥ 100 U/mL.

不同人种乳糜泻患者临床特征的单中心临床分析

目的 总结乳糜泻的临床表现、血清学及病理学特点,并分析欧美及东亚地区乳糜泻患者的异同,探讨中国人群乳糜泻的诊治现状及存在的问题.方法 收集2005年1月至2015年7月北京和睦家医院确诊的来自不同国家的87例乳糜泻患者资料,总结其国籍、发病年龄、临床表现、血清学抗体、内镜下表现、病理结果及治疗随访情况,并对来自不同国家的患者进行对比研究.结果 87例患者中,欧美患者63例（欧美组）,中国和日本患者18例（东亚组）,中东患者6例（中东组）.（1）从年龄构成看,乳糜泻发病的高峰年龄为40 - 60岁.（2）乳糜泻患者中,有慢性腹泻及体重减轻典型表现的患者仅分别占20.7％（18/87）和9.2％（8/87）;一部分患者表现为非特异性症状,如腹痛腹胀[32.2％ （28/87）],甚至便秘[5.7％ （5/87）];13.8％（12/87）患者既往曾被诊断为肠易激综合征（IBS）.欧美组和东亚组患者腹痛腹胀、腹泻、便秘症状的发生率的差异无统计学意义（P值均＞0.05）;但东亚组患者体重减轻、生长发育迟缓、缺铁性贫血、疱疹样皮炎的发生率明显高于欧美组（P值均＜0.05）.（3）IgA型抗麦胶蛋白抗体（AGA）、抗肌内膜抗体（EMA）和抗组织型谷氨酰胺转氨酶抗体（tTGA）在乳糜泻患者中的检出率较高,分别为58.6％ （51/87）、44.8％（39/87）与36.8％（32/87）.（4）消化内镜检查显示,乳糜泻的病变主要位于小肠,从近端小肠至远端小肠病变严重程度逐渐减轻.东亚组患者十二指肠球部、降部的黏膜病变表现较欧美组更为明显,病理组织学显示小肠黏膜萎缩及淋巴细胞增多程度也较欧美组更为严重.（5）87例患者全部接受了去麸质饮食（GFD）治疗,其中81例进行了血清学抗体随诊,8例进行了内镜下小肠黏膜活检的随诊.47例患者于GFD治疗后6-9个月全部血清抗体转阴,34例在12 - 18个月随访时血清抗体全部转阴,且症状明显缓解;8例内镜随诊的患者经GFD治疗1年后,活检显示小肠绒毛萎缩、淋巴细胞浸润等表现较治疗前均有明显改善.结论 乳糜泻患者中具有典型临床表现者仅占一小部分.血清特异性抗体（AGA、EMA和tTGA）在乳糜泻患者中的检出率较高,可以作为筛查手段.GFD治疗对多数乳糜泻患者有效.包括我国在内的东亚患者与欧美患者相比,在临床表现、内镜和病理所见、GFD治疗的反应等方面存在一定差异.乳糜泻在我国可能并非罕见疾病,应该引起临床医生重视,减少漏诊。