New screening tests enrich anti-transglutaminase results and support a highly sensitive two-test based strategy for celiac disease diagnosis

BackgroundThe identification of specific serological algorithms allowing the diagnosis of celiac disease (CD) is a new challenge for both the clinic and the laboratory. We compared the diagnostic accuracy of three new tests proposed for CD screening with that of the well established IgA tTG, and ascertained whether any combination of these tools might enhance accuracy in diagnosing CD.MethodsIn sera from 329 CD and 374 control children, the following were assayed: IgA tTG; IgA/IgG, which identify tTG-gliadin complexes (Aeskulisa Celi Check and CeliCheck IgGA); IgA/IgG, which identify deamidated gliadin peptides and tTG (QUANTA Lite^TM h-tTG/DGP Screen).ResultsWhen specificity was set at 100%, the most sensitive index of CD was IgA tTG (75.7%, cut-off = 100 U), followed by QUANTA Lite^TM h-tTG/DGP Screen (65.3%, cut-off 145 U), Aeskulisa Celi Check (62.6%, cut-off 909 U/mL) and CeliCheck IgGA (59.6%, cut-off 977 U/mL). Three algorithms were obtained by combining IgA tTG with each of the new tests. The algorithm obtained by measuring IgA tTG and QUANTA Lite^TM h-tTG/DGP Screen allowed the correct identification of CD in 78.7% of cases (negative predictive value = 97.3%).ConclusionsThe two-test based strategy could be used for the cost effective diagnosis of CD.     

Prevalence of occult celiac disease in patients with iron-deficiency anemia: a prospective study

BACKGROUND: Occult celiac disease has been reported in 0 to 6% of adults presenting with iron-deficiency anemia. Most prior studies have been retrospective or screened only a selected population of patients with small bowel biopsies. To more accurately define the true prevalence of this disorder in patients presenting with iron-deficiency anemia (with or without stool hemoccult positivity), we initiated this prospective study. METHODS: Esophagogastroduodenoscopy with small bowel biopsies and colonoscopy were performed in all iron-deficiency anemia patients (including those with hemoccult-positive stools) referred to the gastroenterology service during a 2-year period (1998-2000). Inclusion criteria included iron-deficiency anemia as defined by a serum ferritin < 25 ng/ml and anemia with hemoglobin < 12 g/dl. Patients were excluded for documented prior erosive, ulcerative, or malignant disease of the gastrointestinal tract, previous gastrointestinal surgery, overt gastrointestinal bleeding within the past 3 months, or inability to access the duodenum for biopsy. All patients underwent upper endoscopy with more than two biopsies of the distal duodenum and colonoscopy. A serum immunoglobulin A antiendomysial antibody test was to be performed in those patients with a positive small bowel biopsy to confirm the diagnosis of celiac disease. RESULTS: One hundred five of 139 consecutive patients with iron-deficiency anemia met the inclusion criteria and were enrolled in the study. Fifty-seven men (mean age, 51.6 yr) and 48 women (mean age, 54.1 yr) constituted the study population. The demographics of this study population included 36 blacks, 38 Hispanics, and 22 whites. Nine patients were of mixed or unknown ethnic background. Forty-three and eight-tenths percent of the men and 37.5% of women had hemoccult-positive stools, accounting for a total of 40.9% of the study patients. Upper endoscopic findings included gastritis in 22.8%, gastric ulcers in 9.5%, duodenitis in 8.5%, esophagitis in 7.6%, Barrett's ulcer in 2.8%, duodenal ulcer in 2.8%, gastric polyp in 2.8%, and celiac disease in 2.8%. Colonoscopic findings included colon polyps in 21.9%, diverticula in 10.4%, and hemorrhoids in 16.1%. Multiple findings were found in 32.3% of patients, and there were no findings in 28.5% of patients. CONCLUSION: The prevalence of occult celiac disease in this prospective study of patients presenting with iron-deficiency anemia was 2.8%. A significant number of other gastrointestinal lesions amenable to therapy were also found on upper and lower endoscopy in these patients. Given the treatable nature of celiac disease, it should be screened for in patients with unexplained iron-deficiency anemia with or without hemoccult-positive stools.     

Anti-transglutaminase antibody assay of the culture medium of intestinal biopsy specimens can improve the accuracy of celiac disease diagnosis

BACKGROUND: We measured anti-transglutaminase (anti-tTG) antibody in the culture medium of intestinal biopsy specimens from patients with suspected celiac disease (CD) and evaluated the relationship between antibody production and severity of intestinal mucosal damage. METHODS: We performed diagnostic testing for CD on 273 consecutive patients. In addition to routine histologic evaluation of duodenal biopsy specimens, we assayed anti-tTG antibodies in serum and in the culture medium of duodenal biopsy specimens. RESULTS: CD was diagnosed in 191 of the 273 patients. Sensitivity and specificity of the serum anti-endomysium (EmA) and anti-tTG assays were 83% and 85% and 99% and 95%, respectively, and both had 88% diagnostic accuracy. EmA and anti-tTG assayed in the culture medium had 98% sensitivity, 100% specificity, and 98% diagnostic accuracy (vs serum assays; P <0.0001). Twenty-nine CD patient specimens (16%) were negative for serum anti-tTG and EmA; for 24 of these patients, anti-tTG assay of the culture medium was positive. The CD patients whose biopsy specimens were positive for serum antibodies showed the following intestinal histologies: total villous atrophy, 35%; severe villous atrophy, 25%; mild atrophy, 25%; villi with no atrophy but with increased intraepithelial lymphocytes, 15%. None of the CD patients whose specimens were negative for serum antibodies showed total or severe villous atrophy; 77% had mild villous atrophy, and 23% had no villous atrophy but had increased intraepithelial lymphocyte counts. Mild villous atrophy was also seen in specimens from approximately 15% of patients without CD. CONCLUSION: Anti-tTG assay of the culture medium of biopsy specimens can improve the accuracy of CD diagnosis in patients negative for serum antibodies.     

自身免疫抗体检查对乳糜泻诊断的价值和意义

目的评价自身免疫性抗体对乳糜泻诊断的价值和意义。方法对2005年起．来我院就诊的长期慢性腹胀腹泻、具有乳糜泻症状的147例病人进行7种自身免疫性抗体检测：抗麦胶蛋白IgA和IgG抗体、抗肌内膜IgA和IgG抗体、抗网硬蛋白IgG和IgA抗体、抗组织转谷氨酰胺酶IgA抗体。结果有一项抗体阳性38例,二或三项抗体阳性14例。抗麦胶蛋白IgA和IgG抗体、抗肌内膜IgA抗体阳性率分别为53．6％、6413％、32．1％,网硬蛋白IgG及IgA抗体阳性率为0。在部分抗体检查结果阳性并进行小肠黏膜活检的10名患者中,检测到不同程度的黏膜绒毛萎缩变化。结论麦胶蛋白IgA和IgG抗体、肌内膜IgA抗体用于乳糜泻检测有较高的阳性率。     

自身免疫抗体检查对乳糜泻诊断的价值和意义

目的 评价自身免疫性抗体对乳糜泻诊断的价值和意义.方法 对2005年起,来我院就诊的长期慢性腹胀腹泻、具有乳糜泻症状的147例病人进行7种自身免疫性抗体检测:抗麦胶蛋白IgA和IgG抗体、抗肌内膜IgA和IgG抗体、抗网硬蛋白IgG和IgA抗体、抗组织转谷氨酰胺酶IgA抗体.结果 有一项抗体阳性38例,二或三项抗体阳性14例.抗麦胶蛋白IgA和IgG抗体,抗肌内膜IgA抗体阳性率分别为53.6%、64.3%、32.1%,网硬蛋自IgG及IgA抗体阳性率为0.在部分抗体检查结果 阳性并进行小肠黏膜活检的10名患者中,检测到不同程度的黏膜绒毛萎缩变化.结论 麦胶蛋白IgA和IgC抗体、肌内膜IgA抗体用于乳糜泻检测有较高的阳性率.     

Comparison of different salivary and fecal antibodies for the diagnosis of celiac disease

To investigate the detectability and expressiveness of salivary and fecal anti-gliadin (AGA), anti-endomysium (EMA) and anti-tissue-transglutaminase (ATA) antibodies, 127 salivary and 160 fecal samples of healthy volunteers and salivary and fecal samples of 17 patients with histologically proven and 9 patients with suggested celiac disease were investigated in this study. With all salivary parameters and fecal IgA AGA, IgM AGA, IgA EMA and IgG EMA, healthy volunteers and patients showed partially overlapping results. The most promising results in our study with higher concentrations in patients with celiac disease were obtained by fecal scIgA AGA and a combined determination of fecal IgA AGA, IgG AGA and IgM AGA. Further investigations should be performed with fecal IgA EMA and scIgA ATA based on human recombinant tissue-transglutaminase. One patient with histologically proven celiac disease had normal serological but high fecal scIgA AGA and scIgA ATA values. This patient emphasizes the importance of fecal antibody determination for the diagnosis of celiac disease, at least in patients with suggested celiac disease and negative serum antibodies.     

Commentary: advances in the laboratory diagnosis of celiac disease

Anti-endomysial autoantibodies are very useful in the diagnosis and monitoring of celiac disease (gluten-sensitive enteropathy) due to their high sensitivity and specificity for that disorder. The recent discovery that the autoantigen responsible for the endomysial pattern is tissue transglutaminase (tTG) has led to the commercial development of automated enzyme immunoassays for quantitation of that autoantibody. These assays are standardized to provide highly accurate and comparable testing between laboratories for anti-tTG autoantibodies. Celiac disease is a common genetic disease in populations of Europe and the United States. It has a spectrum of expression ranging from silent or mild to severe, with resulting malabsorption that produces multiple-organ system effects due to malnutrition. Many cases miss the diagnosis because the symptoms are not classic or the clinical syndrome is not severe. Because the treatment of celiac disease (avoidance of wheat products) is so effective and inexpensive and because celiac disease is so common in selective populations, a highly reliable test for its detection such as anti-tTG should find wide application in clinical practice.     

Capsule endoscopy in celiac disease: diagnosis and management

Celiac disease occurs in about 1% of the population. Although diarrhea is the classical presentation, the diagnosis of celiac disease is frequently not considered as part of the differential diagnosis of a variety of different symptoms. It is,therefore, imperative that physicians who perform capsule endoscopy, and those who review the images, are aware of the variety of mucosa appearances inpatients who have celiac disease. In addition, studies are needed to determine the role of capsule endoscopy in the diagnosis and management of celiac disease.     

Uselessness of anti-actin antibody in celiac disease screening

BACKGROUND: Serum anti-actin IgA antibodies (AAA) were identified in patients with celiac disease (CD), and a close correlation emerged between the presence of AAA and mucosa damage, but test for AAA found in celiacs have a wide range of sensitivity and specificity values. AIM: To compare 1) the sensitivity and specificity of untreated, calcium-chelated and heated sera from 102 celiacs, 52 sick patients and 103 healthy controls in the determination of AAA, and 2) the reliability of AAA with anti-transglutaminase antibodies (anti-tTG) in diagnosing celiac disease and in predicting intestinal damage. The intestinal derived AAA was isolated by using the phage-display library technique. RESULTS: Treated sera was significantly more sensitive than untreated (p=0.0001), and showed a significant correlation between AAA and the three degrees (3a, 3b, 3c) of intestinal damage (p=0.01). Sensitivity and specificity values of anti-tTG assay were higher than the AAA assay, and anti-tTG serum-concentration was only significantly correlated with more severe (3b and 3c) intestinal damage degrees. AAA isolated by phage display showed similar results of serum AAA in immunofluorescence assay. CONCLUSIONS: Notwithstanding correlation between AAA and celiac disease, AAA assay, also after treatments, has little to offer in screening for CD compared to the well-established anti-transglutaminase assay.     

Against the grain: an overview of celiac disease

PURPOSE: To review the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of celiac disease (CD). DATA SOURCES: Review of literature using Pub Med and Access Medicine. The following search terms were used: celiac disease, malabsorption syndromes, diarrhea, and gluten-free diet (GFD). There was no limitation placed on publication year. Only articles written in English were included. CONCLUSIONS: CD is a chronic systemic autoimmune disorder triggered in genetically susceptible individuals by the ingestion of gluten proteins (wheat, barley, and rye). CD often presents atypically, and diagnosis delays are common. Currently, the only effective treatment for CD is strict adherence to a GFD. This is a difficult diet to comprehend and follow. Adherence to a GFD requires ongoing education and support from a multidisciplinary healthcare team, support groups, family, and friends. IMPLICATIONS FOR PRACTICE: Once considered a rare disease of childhood, CD is now recognized as a common disorder that can occur at any age. Clinicians need to be cognizant of risk factors, clinical manifestations, conditions, and complications associated with CD in order to make a timely diagnosis, ameliorate symptoms, and minimize disease complications.     

Guidelines for the diagnosis and treatment of celiac disease in children

Jennifer, age 2 years, is being seen for her regular 2-year well child visit. You note her weight is only at the 5% and has been dropping percentiles over the past year When you ask her mother about Jennifer's diet, she reports Jennifer is a "picky eater" and often complains of a "stomach ache." Her mother reports her stomach looks "bloated. " Steven, age 7 years, is brought into the clinic because of recurrent abdominal pain with occasional constipation or diarrhea. Steven's mother had been told in the past that he probably had "irritable bowel syndrome" but changes in his diet, occasional use of a laxative, and relaxation techniques have not improved his symptoms. Rebecca, age 12 years, is brought into your clinic because her mother has recently learned that two first cousins have been diagnosed with celiac disease. She is wondering if Rebecca should be screened for this condition since she has heard it runs in families.     

Role of anti-transglutaminase (anti-tTG), anti-gliadin, and anti-endomysium serum antibodies in diagnosing celiac disease: a comparison of four different commercial kits for anti-tTG determination

The aims of this study were: (1) to compare the diagnostic efficacy for celiac disease (CD) diagnosis of serum determination of anti-gliadin (AG) (IgA and IgG) and anti-endomysium (AE) with that of anti-transglutaminase (AtTG); and (2) to compare the accuracy of four different assays to measure AtTG. We studied 72 children: the histological diagnosis of CD was made in 38 cases and excluded in the remaining 34 children. In fasting sera we measured AE, AG-IgA and IgG, and AtTG, the latter with four different commercial kits (Eurospital, Medipan, Inova, Arnika). Moreover AtTG was measured in a group of 58 CD children after a gluten-free diet. AE was positive in all but 1 case of CD patients (sensitivity = 97%); false positive results were found in 1/34 controls (specificity = 97%). When a specificity of 95% was fixed, the sensitivities were 97% for AE, 83% for AG-IgA, and 63% for AG-IgG; the sensitivities of anti-tTG were 90, 84, 84, and 75% when measured with Eurospital, Medipan, Inova, and Arnika kits respectively. The new AtTG seems to be accurate enough to be proposed as a noninvasive diagnostic tool for CD diagnosis; the 4 kits analyzed showed similar diagnostic efficacy.     

Endoscopic and histological findings in the duodenum of adults with celiac disease before and after changing to a gluten-free diet: a 2-year prospective study

BACKGROUND AND STUDY AIMS: Published follow-up data on small-intestinal recovery in patients with celiac disease are scarce and contradictory. This is especially the case for adult patients, who often show incomplete histological recovery after starting a gluten-free diet (GFD). We conducted a 2-year prospective study to evaluate the effectiveness of a GFD in improving the endoscopic and histological duodenal findings in adults with celiac disease. PATIENTS AND METHODS: We studied 42 consecutive adults with newly diagnosed celiac disease (13 men, 29 women; mean age 32.7 years, range 15 - 72 years). All the patients underwent esophagogastroduodenoscopy and small-bowel biopsy. We devised our own grading system for the endoscopic appearance of the duodenum, which ranged from "normal" appearance to "mild", "moderate", or "severe" alterations. Small-bowel biopsies were obtained from the second part of the duodenum (and from the duodenal bulb when it had a micronodular appearance). The histopathological appearances were described according to modified Marsh criteria. RESULTS: A normal endoscopic appearance in the duodenum was found in 5/42 patients (11.9 %) at entry and in 32/42 patients (76.2 %) after 2 years on a GFD. Subdividing the patients according to age, patients aged from 15 years to 60 years showed significant improvement within 12 months ( P < 0.0001 for patients aged from 15 years to 45 years; P < 0.003 for patients in the 46 years to 60 years group), whereas the improvement in endoscopic findings in patients older than 60 years was not statistically significant, even 24 months after starting the GFD. "Normal" histology was reported in none of the patients at entry, but in 25 patients (59.5 %) after 24 months on a GFD, but this parameter did not show a significant improvement until the patients had been on the GFD for 12 months ( P < 0.0001). Only the younger patients (5 - 30 years) showed significant improvement of histology within 12 months ( P < 0.034); older patients (>30 years) showed histological improvement but this was not statistically significant, even after 24 months on a GFD. CONCLUSIONS: This study shows for the first time that endoscopic recovery is faster than histological recovery in adults with celiac disease who go on a GFD. Moreover, older patients showed incomplete endoscopic and histological recovery even 24 months after starting a GFD. We therefore advise, as a minimum recommendation, that follow-up biopsies should be taken 1 - 2 years after starting a GFD in adults with celiac disease.     

Antibodies against synthetic deamidated gliadin peptides as predictors of celiac disease: prospective assessment in an adult population with a high pretest probability of disease

BACKGROUND: Noninvasive serologic tests have shown high diagnostic accuracy for celiac disease (CD) in selected populations. Our aim was to determine prospectively the performance of CD-related serology in individuals undergoing intestinal biopsy because of clinical suspicion of small-bowel disorders. METHODS: We enrolled 141 unselected consecutive adult patients attending a small-bowel disease clinic. Patients underwent endoscopy and biopsy; serum samples were obtained at that time for measurements of anti-tissue transglutaminase (a-tTG), IgA and IgG anti-deamidated gliadin-related peptide (a-DGP), and IgA antiactin antibodies (AAAs). Characterization of patients was based on histological criteria (Marsh type II lesion or greater). RESULTS: The prevalence of CD was 42.5%. Sensitivity, specificity, and positive and negative predictive values were >90% for most assays. Diagnostic accuracy based on ROC curve analysis was similar for all assays [area under the curve (95% CI): 0.996 (0.967-0.998) for a-tTG, 0.995 (0.964-0.998) for IgA a-DGP, 0.989 (0.954-0.999) for IgG a-DGP, 0.996 (0.966-0.998) for blended conjugated of IgA + IgG a-DGP in a single assay, and 0.967 (0.922-0.990) for AAA]. The combinations of 2 tests, IgG a-DGP plus IgA a-tTG or the single blended conjugate detecting IgA + IgG a-DGP plus IgA a-tTG had 100% positive and negative predictive values if concentrations of both tests in either combination were above or below the cutoff. CONCLUSIONS: In a population with high pretest probability, the newly developed a-DGP tests have diagnostic accuracy that is at least equivalent to that of established assays.     

Coeliac disease screening in children: assessment of a novel anti-gliadin antibody assay

Coeliac disease (CD) screening has progressed rapidly with tissue transglutaminase (TTG), the screening tool of choice. However, TTG may be unreliable in young children and advances in CD etiology understanding have seen improvements in anti-gliadin (AGA) assay technology. The aim of this study was to investigate the utility of an updated and refined AGA (Neogliadin) assay for CD screening in children with gastrointestinal symptoms. Children attending the Sydney Children's Hospital, Randwick, with gastrointestinal symptoms had sera collected and assayed by Neogliadin and commercial TTG assays in addition to the usual clinical work-up. One hundred and fifteen children were recruited in which 32 were diagnosed with CD. AGA-IgA screening by Neogliadin showed improved sensitivity (83%) and specificity (91%) but did not eclipse the sensitivity (93%) and specificity (90%) of TTG-IgA screening. In the children diagnosed with CD, 7 were identified as younger than 5 years of age with 4/7 AGA-IgA positive, 5/7 AGA-IgG positive, and 6/7 TTG-IgA positive. The updated Neogliadin IgA assay does not improve on the accuracy achieved by TTG screening. TTG appears to be a suitable screening tool for children younger than 5 years of age although this preliminary finding requires confirmation.     

Bronchoscopy and tuberculostearic acid assay in the diagnosis of sputum smear-negative pulmonary tuberculosis: a prospective study with the addition of transbronchial biopsy.

A prospective study of the efficacy of bronchoscopy and tuberculostearic acid assay in the diagnosis of sputum smear-negative pulmonary tuberculosis (TB) was carried out in 39 patients with symptoms and radiographic changes suggestive of active pulmonary TB. The diagnosis of TB was confirmed in 15 patients, probable TB was diagnosed in eight and 16 patients did not have TB. An early diagnosis of TB was made by bronchoscopy in six patients (40 per cent). Culture of sputum obtained before bronchoscopy was positive in nine patients (60 per cent) while combined with bronchoscopy specimens, a positive mycobacterial culture was obtained in 12 patients (80 per cent). Mycobacteria were cultured from transbronchial biopsy specimens from five patients (33 per cent) but none of these was exclusively positive. Histological examination of transbronchial biopsy tissue was diagnostic of TB in four patients and it was the exclusive means of early diagnosis in two. Transbronchial biopsy also provided an alternative diagnosis in four other patients. Tuberculostearic acid assay had a sensitivity of 0.40 in bronchial aspirate, 0.80 in bronchoalveolar lavage fluid, and 0.27 in transbronchial biopsy specimens: the combined result was 0.87. In nine patients with pulmonary TB in whom an early diagnosis could not be made, the tuberculostearic acid assay was positive in seven (78 per cent). We conclude that bronchoscopy with bronchoalveolar lavage and transbronchial biopsy is helpful in providing early diagnosis and positive culture results. Assay of tuberculostearic acid in bronchoalveolar lavage fluid is a useful adjunct to early diagnosis. However, mycobacterial culture and assay of tuberculostearic acid in transbronchial biopsy specimens have little diagnostic value.     

ELISA 与胶体金免疫层析法检测血清抗 CCP 抗体在 RA 诊断中的比较

目的：比较胶体金免疫层析法和酶联免疫吸附试验（ELISA ）检测血清抗环瓜氨酸肽（CCP）抗体结果差异性。方法采用胶体金免疫层析法和 ELISA 法同步检测110例 RA 患者和110例健康体检者的抗 CCP 抗体。结果2种方法经配对χ2检验,差异有统计学意义（χ2＝174．354,P＜0．01）;K ap pa值评价（K ＝0．890,P ＜0．01）显示2种检测方法具有高度一致性。 ELISA 法灵敏度和特异度分别为83．64％和92．73％,均优于胶体金免疫层析法。结论2种方法检测血清抗 CCP 抗体存在差异,ELISA 法的灵敏度和特异度均较高,优于胶体金免疫层析法。