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Biomedical subjects

Julio C Bai

Publications and source records attributed to Julio C Bai.

13 recordsLinked to original sources

Accuracy of testing for antibodies to synthetic gliadin-related peptides in celiac disease.

BACKGROUND & AIMS: Our aim was to explore the diagnostic value of a newly developed synthetic peptide antibody assay addressing specific synthetic gliadin-derived deamidated peptides (AGA II) for the diagnosis of celiac disease (CD). METHODS: We assayed serum samples obtained prospectively at diagnosis from a population of 92 consecutive adult patients with CD and 113 non-CD controls. Patients were reevaluated after 6 months (n = 56) and 1 year (n = 20) of treatment. All patients and controls underwent intestinal biopsy and a set of CD-related serology tests. A newly developed enzyme-linked immunosorbent assay (ELISA) for detecting IgA and IgG antibodies against synthetic deamidated gliadin epitopes was used. RESULTS: At diagnosis, sensitivity and specificity were 94.6% and 99.1% for AGA II IgA and 92.4% and 100% for AGA II IgG. Absolute values and the proportion of positive samples for both antibodies were significantly reduced at 6 months (P < .0000) and 1 year (P < .001) after initiation of a gluten-free diet. Compared with conventional AGA, the peptide antibodies had greater sensitivity, specificity, positive and negative predictive values, accuracy, and likelihood ratios. Compared with antitissue transglutaminase antibodies, AGA II had similar sensitivity but greater specificity and predictive values, better likelihood ratios, and an excellent agreement (kappa statistic = .92). CONCLUSIONS: This study assessed the value of an ELISA assay in detecting antibodies to gliadin-related peptides. This assay appears to be a reliable tool for diagnosing CD and suggests promising accuracy that may be very useful in clinical practice.

Adolescent↗

Celiac disease serology in dermatitis herpetiformis. Which is the best option for detecting gluten sensitivity?

BACKGROUND: Dermatitis herpetiformis (DH), a well-established gluten-sensitive skin disorder presenting variable degrees of enteropathy, constitutes a very useful model in order to assess the utility of the celiac disease (CD)-related serology in patients with mild intestinal damage. OBJECTIVE: Our aim was to explore comparatively the performance of a panel of CD-related serologic tests in patients with DH. METHODS: We assessed a series of 18 consecutive patients with skin biopsy proven DH presenting the overall spectrum of intestinal damage ranging from normal mucosa (n = 6) to total villous atrophy (TVA) (n = 6) through partial villous atrophy (PVA) (n = 6). Sera were obtained from all patients while consuming a gluten containing diet. Serologic tests were antiendomysial, anti-tissue transglutaminase and antigliadin antibodies, and newly developed tests detecting both antibody isotypes (IgA and IgG) against deamidated synthetic gliadin-derived peptides (a-GDP). RESULTS: Serologic tests had a variable behaviour depending on the degree of enteropathy. While the majority of tests detected patients with TVA, only 50% of those with normal histology had positive assays. Patients with PVA had discordant results. Classical CD-specific tests were positive in only some patients with mild damage while all of them were identifed by a single assay detecting both isotypes of a-GDR CONCLUSION: The detection of a-GDP antibodies was the most reliable tool in order to identify gluten sensitivity in DH patients presenting a wide range of intestinal damage. Further studies should explore if these findings can be extrapolated to patients with CD having mild enteropathy.

Adolescent↗

Bones in coeliac disease: diagnosis and treatment.

Coeliac disease predisposes to metabolic osteopathy. The entity of bone loss is higher in patients with malabsorption at diagnosis but it is also present in asymptomatic or poorly symptomatic patients, occurring in roughly half of them. Calcium malabsorption and the release of proinflammatory cytokines, activating osteoclasts, represent the main mechanisms responsible for bone derangement. In coeliacs, the presence of an increased fracture risk was recently questioned and its importance on clinical grounds was reconsidered, in view of the fact that gluten-free diet generally improves bone mass and, consequently, reduces fracture risk. However, gluten-free diet rarely normalizes bone mass and the co-administration of mineral active drugs may be useful in a subgroup of coeliacs.

Bone Density↗

[Activity index in Crohn's disease].

The gold standard to quantify Crohn's disease activity is still not defined and a world consensus to unify criteria is necessary. Criticism has been directed towards every existing indexes. We summarize some of the currently used criteria for the assessment of disease activity, point out the controversies and issues that will need further investigations, and discuss their usefulness based on our experience.

Biomarkers↗

Significance of smooth muscle/anti-actin autoantibodies in celiac disease.

BACKGROUND/AIM: Smooth muscle antibody (SMA) specific for the protein actin, a major component of the cytoskeleton of epithelial cells, is one of the most prevalent non-organ specific autoantibodies in the serum of celiac disease (CD) patients. Our aim was to explore the clinical relevance of the presence of IgA type anti-actin antibody (AAA) and SMA in a series of patients with CD. METHODS: We evaluated frozen serum samples collected at diagnosis from 92 adult patients with CD and 52 control individuals in whom CD was excluded. Patients were re-evaluated a median time of 5 yr after treatment. IgA type AAA was detected using a modified commercial ELISA assay and IgA SMA was detected using indirect immunofluorescence on primate esophagus substrate. RESULTS: At diagnosis, samples from CD patients had significantly higher AAA values than controls (p<0.00001). While all active CD patients had serum AAA values over the cut-off for healthy controls, we observed a very significant reduction of these antibodies after treatment (p>0.0001). AAA had a highly significant correlation with both, tissue, transglutaminase (r=0.62) and antigliadin (r=0.60, p<0.00001) antibodies as well as the severity of the intestinal injury (p<0.05). SMA was detected in sera of 35 consecutive CD patients. At diagnosis, SMA positive patients had significantly higher values of AAA (p<0.0002), increased number of autoimmune disorders (p<0.04), delayed menarche (p<0.04), lower hemoglobin levels (p<0.01), increased fecal a-I antitrypsin clearance (p<0.01) and more severe diarrhea (p<0.06). We also detected a trend to more severe complications at follow-up (p=0.059). CONCLUSIONS: Based on our findings we suggest that the presence of increased IgA AAA serum levels is a highly sensitive marker of the disturbed architecture of intestinal epithelial cells of CD patients with a potential relevance to diagnosis and follow-up. The presence of SMA seems to define a distinct subset of CD patients with a more severe clinical outcome.

Actins↗

Stratification of bone fracture risk in patients with celiac disease.

BACKGROUND AND AIMS: Our objective in this cross-sectional, case-control study was to gain insight into celiac osteopathy by examining a well-defined cohort of patients with a wide clinical spectrum of the disease. METHODS: We studied 148 unselected celiac patients and 296 (1:2) age- and sex-matched controls diagnosed with functional gastrointestinal disorders. Based on the clinical history, 53% were classically symptomatic, 36% had subclinical celiac disease, and 11% were silent, detected by screening. The fracture information was obtained through an in-person interview using a pre-designed questionnaire. RESULTS: Classically symptomatic patients had an increased number of fractures in the peripheral skeleton (47%) compared with age- and sex-matched controls (15%; odds ratio, 5.2; 95% confidence interval, 2.8-9.8). However, fractures in subclinical/silent celiac cases (20%) were no different from those in controls (14%; odds ratio, 1.7, 0.7-4.4). Compared with the subclinical/silent group, a significantly greater prevalence of fractures was detected in classically symptomatic patients (odds ratio, 3.6, 1.7-7.5). Compared with controls, celiac disease patients had significantly more fractures produced by mild trauma (P < 0.01), but there were no differences in the severity of trauma events that induced fractures. Mean bone density femoral neck z score was higher for subclinical/silent cases compared with classically symptomatic patients (P < 0.05). CONCLUSIONS: Celiac patients show a very wide variation in fracture risk, with increased risk in classically symptomatic patients. Diagnostic and therapeutic strategies to prevent bone loss and fracture should be preferentially used in the subgroup of patients with classic clinical disease.

Adolescent↗

Whipple's disease.

Whipple's disease is a rare multisystemic infectious disorder affecting predominantly middle-aged men. Clinical manifestations are very variable with a very long, insidious, prediagnostic course. Weight loss, chronic diarrhea, arthralgias, and low-grade fever are characteristic features in most patients. Although gastrointestinal compromise is very common, atypical clinical forms are being increasingly recognized. Although a bacterial cause was strongly suggested for many years, the infectious agent was elusive until recently. The bacillus that was classified as an actinomycete was named Tropheryma whipplei and has singular characteristics. It presents affinity for the periodic acid-Schiff stain, but it is negative for Ziehl-Neelsen staining and has a characteristic trilamellar cell wall. Its genetic material has been recently sequenced, and culture was finally performed on a human fibroblast cell line. Pathological specimens show macrophage infiltration with mostly intracellular invasion of live bacteria. Immunologic factors, such as a subtle defect of cellular immunity possibly specific for the Whipple's bacterium, are believed to play a role in pathogenesis. The diagnosis requires the histologic assessment of diseased tissue, showing the characteristic infiltration, as a first approach, and confirmatory tests such as electron microscopy and/or polymerase chain reaction. Antibiotic treatment is mandatory and leads to a rapid clinical improvement and remission in most patients. Although the rationale for treatment is largely empiric, current recommendations include a 2-week parenteral therapy (third generation cephalosporin) followed by a long-term therapy with trimethoprim-sulphamethoxazole. This approach has been shown to reduce the number of relapses and was effective for prevention and/or treatment of the neurologic compromise.

Anti-Bacterial Agents↗

Analysis of the structure and strength of bones in celiac disease patients.

OBJECTIVE: The aim of this study was to gain insight into the pathogenesis of bone mass loss and weakening affecting patients with celiac disease, according to the new concepts of bone structure/strength and muscle/bone interrelationships. METHODS: We studied serum variables and tomographic indicators of bone structure and strength and regional muscle masses in a series of patients at diagnosis and after 1 yr on a gluten-free diet and in gender- and age-matched controls. RESULTS: At diagnosis, serum levels of calcium and vitamin D were low, and indicators of parathyroid hormone activity and bone formation and resorption were increased. All these parameters were normalized by treatment. Peripheral quantitative CT scans of the distal radius revealed that cortical bone was generally more affected than trabecular bone. The cross-sectional area (CSA) and the volumetric mineral content and density of cortical bone (indicators of cortical tissue mass and mechanical quality), and moments of inertia (CSMI, indicator of the bone architectural design) were in the lower end of normal range in men, and below that in 50% of women. In men, the CSMI/CSA ratio (indicator of the architectural efficiency of distribution of the available cortical tissue) was lower than expected and remained unchanged after treatment. In women, the baseline ratio was normal, but both the ratio and the CSMI were low at diagnosis and normalized after treatment. Both baseline values and the treatment-induced changes of cortical and trabecular bone in the radius and the axis (L3) correlated inversely with serum parathyroid hormone levels. Baseline values or changes in the mineral content of the vertebral bone correlated with the CSA of psoas and spine-extensor muscles. Multiple regression analyses showed that metabolic and mechanical parameters were independent determinants of different aspects of the vertebral bone weakening. CONCLUSIONS: Our results show that bone weakening in celiac disease might result from both 1) a metabolic disturbances of bone remodeling affecting trabecular and cortical bone masses and the mechanical quality of the bone material, and 2) a reduction of muscle strength impairing the modeling-dependent optimization of bone architectural design and mass of cortical bone. Dietary treatment seems to correct almost exclusively the metabolically induced disturbances, which were predominant in women.

Adult↗

Bone-specific antibodies in sera from patients with celiac disease: characterization and implications in osteoporosis.

Osteopenia and osteoporosis are well-known complications detected in celiac disease patients with still obscure pathogenesis. In the present study we investigated the presence of circulating anti-bone autoantibodies in patients with celiac disease and explored their role in the associated bone disease. We evaluated serum samples from 33 patients at the time of diagnosis and from 20 of them after treatment. Sera from patients with inflammatory bowel disease (n = 9), nonceliac osteoporotic (n = 18), and healthy individuals (n = 10) were used as controls. The presence of IgA specific anti-bone antibodies was first investigated using indirect immunofluorescence on cryosections of fetal rat tibia (20-day pregnancy). Furthermore, samples were homogenized and total tissue extracts were subjected to Western blot analysis to confirm immunoreactivity. At diagnosis, sera from 51.5% (17/33) of celiac patients had antibodies that recognized antigenic structures in chondrocytes and the extracellular matrix along mature cartilage, bone interface, and perichondrium of fetal rat bone. Among controls, only two osteoporotic patients showed very low titles of anti-bone autoantibodies. The immunostaining was localized in areas where an active mineralization process occurred and was similar to the distribution of the native bone tissue transglutaminase. The frequency of patients with positive baseline titers of anti-bone antibodies diminished significantly after treatment (P = 0.048). Western blot assays confirmed the presence of autoantibodies in sera from patients with a positive immunofluorescence staining. Autoantibodies recognized a major protein band on tissue extracts with a molecular weight of 77-80 kDa, which could be displaced when sera were preadsorbed with human recombinant tissue transglutaminase. We provide original evidence that patients with celiac disease have IgA-type circulating autoantibodies against intra- and extracellular structures of fetal rat tibia. Our findings suggest that these antibodies recognize bone tissue transglutaminase as the autoantigen, and based on the localization of the immunoreactivity we speculate that they might have an active role in the pathophysiology of celiac disease-associated bone complications.

Adult↗

Azathioprine in refractory sprue: results from a prospective, open-label study.

OBJECTIVE: Refractory sprue is a rare and severe malabsorptive disorder that mimics celiac disease but is refractory to a gluten-free diet and is without initial evidence of overt lymphoma. Treatment is largely empiric and often ineffective, with steroids and immunosuppression being the mainstream therapeutic options. The aim of this study was to evaluate prospectively the effect of azathioprine on a group of patients diagnosed with refractory sprue. METHODS: We studied seven consecutive patients (five women and two men) with a well-defined diagnosis of refractory sprue and a lack of response to oral or parenteral steroids. At diagnosis, five patients had endoscopic evidence of ulcerative jejunitis, and five underwent exploratory laparotomy for exclusion of malignancies. The characteristic monoclonal TCRgamma gene rearrangement was shown in five of six patients studied. Patients were treated for a mean of 11 months (range 8-12 months), and clinical, biochemical, molecular, and histological parameters were reassessed at the end of the trial. The study was a prospective, open-label, non-placebo-controlled study using azathioprine (2 mg/kg/ day) plus oral prednisone (1 mg/kg/day). A gluten-free diet (n = 7) as well as enteral (n = 6) and parenteral nutrition (n = 5) were administered during the trial. RESULTS: After treatment, five patients had a complete clinical remission, and biochemical and nutritional parameters were significantly improved. Steroids were tapered after the onset of azathioprine, and no patient was on steroids at the end of the trial. Intestinal histology improved significantly in all cases (normal histology in three cases and minor infiltration in the lamina propria in two). Two patients did not respond to treatment at any time and died in months 10 and 9, of an irreversible ventricular fibrillation and sepsis, respectively. No overt lymphoma was demonstrated during the follow-up. CONCLUSIONS: The present study confirms earlier anecdotal reports on the efficacy of azathioprine in refractory sprue, with clear clinical and histological improvement shown in most patients. However, monoclonality persisted after treatment. We consider that a larger number of patients should be evaluated before a definitive recommendation is adopted for use of this drug in refractory sprue.

Adult↗

Value of a screening algorithm for celiac disease using tissue transglutaminase antibodies as first level in a population-based study.

OBJECTIVE: Serological screening for celiac disease (CD) can detect a large number of otherwise undiagnosed patients based on the sequential evaluation of serological tests and intestinal biopsy. The aim of this study was to compare the screening value for CD of two different protocols for the same community-based population. METHODS: We screened 1,000 consecutive subjects (497 women, age range 16-71 yr) attending a centralized laboratory for obligatory prenuptial blood tests. Serum samples obtained from all subjects were processed using two different protocols: I) a three-level classic screening consisting of the parallel use of IgG and IgA antigliadin antibodies as first level, followed by endomysial antibodies and total serum IgA for positive patients, and finally, intestinal biopsy of positive patients; and 2) a study screening protocol consisting of the parallel use of a commercial guinea pig antitissue transglutaminase antibody and total serum IgA as first line, endomysial antibodies (type IgA and/or IgG) for positive patients, and finally, intestinal biopsy. RESULTS: The classic screening protocol identified five subjects who were eligible for intestinal biopsy, which confirmed the presence of CD in all (prevalence 5.0 x 1,000, 95% CI = 1.6-11.6). Using the study algorithm, we detected seven new patients including the five patients detected by the first protocol (prevalence 7.0 x 1,000, 95% CI = 2.8-14.4). The two additional patients diagnosed using the proposed algorithm had positive IgG antigliadin antibodies and normal total serum IgA and were not detected by the classic protocol. Both patients were endomysial antibodies positive. The comparative analysis showed that the classic approach was more expensive (U.S. $4,687 per new patient detected) compared with the proposed study algorithm (U.S. $3,006). CONCLUSIONS: Our data showed that a new screening protocol using antitissue transglutaminase as first line followed by endomysial antibodies is a cost-effective screening and yielded more realistic figures of prevalence for CD in a community setting than the classic three-level sequential evaluation using antigliadin antibodies.

Adolescent↗