Erica Fiorini

Serological tests in gluten sensitivity (nonceliac gluten intolerance).

Goals: To characterize the serological pattern of gluten sensitivity (GS) and to compare it with that found in celiac disease. Background: GS has recently been identified as a new clinical entity included in the spectrum of gluten-related disorders, but it is still lacking of diagnostic markers. Study: Sera from 78 patients with GS and 80 patients with celiac disease were retrospectively assessed for immunoglobulin (Ig)G/IgA antigliadin antibodies (AGA), IgG deamidated gliadin peptide antibodies (DGP-AGA), IgA tissue transglutaminase antibodies (tTGA), and IgA endomysial antibodies (EmA). Results: IgG AGA were positive in 56.4% of GS patients and in 81.2% of celiac patients, with high antibody titers in both groups. IgA AGA were detected in 7.7% of GS patients and in 75% of celiac patients, showing lower enzyme-linked immunosorbent assay activities in GS than those found in celiac disease. Only 1 of the 78 patients with GS was positive for IgG DGP-AGA (detected in 88.7% of patients with celiac disease). IgA tTGA and IgA EmA were negative in all GS patients, whereas their positivity in celiac patients was 98.7% and 95%, respectively. Patients with GS displayed a variegated clinical picture with intestinal and extraintestinal symptoms (abdominal pain, bloating, diarrhea, constipation, foggy mind, tiredness, eczema/skin rash, headache, joint/muscle pain, numbness of legs/arms, depression, and anemia) together with normal or mildly abnormal small intestinal mucosa. Conclusions: The serological pattern of GS is characterized by IgG AGA positivity in more than half of cases associated to IgA AGA in a few patients, but without EmA, tTGA, and DGP-AGA, which are the specific markers of celiac disease.

Plasma Citrulline Concentration: A Reliable Marker of Small Bowel Absorptive Capacity Independent of Intestinal Inflammation

OBJECTIVES:Postabsorptive plasma citrulline concentration has been proposed as a reliable marker of small bowel absorptive capacity in short bowel patients. The aim of this study was to address the potentially confounding impact of intestinal inflammation.METHODS:Fifty-five patients were selected according to diagnosis, small bowel length, and degree of bowel inflammation. (a) Crohns disease (CD) with massive small bowel resection leaving ≤50 cm (N = 6), (b) CD with 50–150 cm remaining (N = 9), (c) CD with no resection but active inflammation (high C-reactive protein [CRP] and Crohns Disease Activity Index [CDAI] >220) (N = 7), (d) CD without resection or active inflammation (normal CRP and CDAI <150) (N = 9), (e) mesenteric infarction (MI) with resection leaving ≤50 cm (N = 6), (f) MI leaving 50–150 cm (N = 6), (g) active celiac disease (N = 6), (h) healthy volunteers (N = 6). Postabsorptive fasting plasma citrulline was measured using reverse-phase, high performance liquid chromatography. Absorptive capacity and permeability were also measured after oral sugar-mix ingestion (5 g lactulose, 1 g L-rhamnose, 0.5 g D-xylose).RESULTS:The plasma citrulline strongly correlated with small bowel length (P < 0.0001) and xylose absorption (P < 0.001). No correlation was found with CDAI, permeability, CRP, albumin, sedimentation rate, white cell count, or platelet count. Citrulline was significantly higher (P < 0.0004) in CD and MI patients with a remnant small bowel length of 50–150 cm (mean 21.0 μmol/L) than in those with length ≤50 cm (mean 9.2 μmol/L).CONCLUSIONS:Plasma citrulline concentration is a simple and reliable surrogate for small bowel absorptive capacity and is not influenced by intestinal inflammation.

Deamidated gliadin peptide antibodies as a routine test for celiac disease: a prospective analysis.

Goals This study was designed to establish whether deamidated gliadin peptide antibodies (DGP-AGA) could improve the serologic workup for celiac disease (CD). Background The best serologic approach for CD screening is currently based on the combined detection of tissue transglutaminase (tTGA), endomysial (EmA), and gliadin antibodies (AGA). Study One hundred forty-four consecutive patients with gastrointestinal and extraintestinal signs suggestive for CD were investigated using serologic tests, that is, IgG and IgA DGP-AGA, IgA tTGA, IgA EmA, and duodenal biopsy. Results Forty-eight out of 144 patients (33%) had CD with different severity of villous atrophy. IgA tTGA showed 93.7% sensitivity compared with 91.6% for IgA EmA, 84.3% for IgA DGP-AGA, and 82.3% for IgG DGP-AGA. Of the 3 cases negative for IgA tTGA, IgA EmA, and IgA DGP-AGA, 2 had total IgA deficiency, although both were positive for IgG DGP-AGA. IgG DGP-AGA showed a very high specificity for CD (98.9%), not only superior to IgA DGP-AGA (79.8%), but also to IgA tTGA (96.6%) and very close to IgA EmA (100%). Conclusions Our prospective study shows that the combined search for IgA tTGA and IgG DGP-AGA provides the best diagnostic accuracy for CD, allowing the identification of all CD cases---except one---with a very high specificity. The serologic workup for CD screening could be significantly improved by the routine introduction of IgG DGP-AGA together with IgA tTGA, thus reducing the number of tests and with an obvious advantage in terms of cost-efficacy.

Prevalence of Celiac Disease in Children With Type 1 Diabetes Mellitus Increased in the Mid-1990s: An 18-year Longitudinal Study Based on Anti-endomysial Antibodies

Between 1987 and 2004, 331 consecutive children, all newly diagnosed with type 1 diabetes mellitus in our pediatric clinic, underwent repeated serological screening for celiac disease (CD) by means of anti-endomysial antibodies, measured prospectively between 1994 and 2004, and retrospectively, using frozen banked serum, between 1987 and 1993. There were 22 cases (6.6%) of biopsy-proven CD among the 331 diabetic children. The prevalence of CD was significantly (P = 0.015) higher after 1994 (10.6%) than before 1994 (3.3%). The rapid change in the risk of CD among Italian diabetic children that occurred in the mid-1990s could be related to changes in environmental factors, namely, eating habits and viral infections.

Old and new serological tests for celiac disease screening

Evaluation of: Lewis NR, Scott BB. Meta-analysis: deamidated gliadin peptide (DGP) antibody and tissue transglutaminase (tTG) antibody compared as screening test for celiac disease. Aliment. Pharmacol. Ther. 31(1), 73–81 (2010). In celiac disease (CD), deamidation of gliadin peptides, induced by tissue transglutaminase (tTG), generates novel antigenic epitopes evoking a specific immune response. Serological tests based on the detection of antibodies to deamidated gliadin peptides (DGP) have been developed with very promising results in terms of sensitivity and specificity for CD screening. In the present study, a meta-analysis of studies published from 1998 to 2008 was designed to compare the performance of DGP antibodies with that of tTG antibodies, the validated and routinely employed test for CD screening. The authors have limited their analysis to IgA class antibodies underlining that most of the considered studies had methodological imperfections, especially ascertainment bias. The results of this meta-analysis indicated that the pooled sensitivities for DGP and tTG antibodies were 87.8% (95% CI: 85.6–89.9) and 93% (95% CI: 91.2–94.5), respectively, and the pooled specificities were 94.1% (95%CI: 92.5–95.5) and 96.5% (95% CI: 95.2–97.5), respectively. In summary, although both tests represent a very good tool for identifying celiac patients, tTG antibodies display a higher predictive value than DGP antibodies, and must still be considered the best serological test for CD screening.

Sensorineural hearing loss and celiac disease: A coincidental finding

BACKGROUND Celiac disease (CD) can be associated with a variety of extraintestinal manifestations, including neurological diseases. A new neurological correlation has been found between CD and sensorineural hearing loss (SNHL). OBJECTIVE To verify the association between SNHL and CD, and to establish whether the neurological hearing impairment in CD is related to nonorgan-specific and antineuronal antibodies, as well as the presence of autoimmune disorders. METHODS A sample of 59 consecutive biopsy- and serologically proven CD patients were studied. Among CD patients, 11 were newly diagnosed and 48 were on a gluten-free diet. Hearing function was assessed by audiometric analysis in all CD patients as well as in 59 age- and sex-matched controls. Patients were tested for a panel of immune markers including nonorgan-specific autoantibodies and antineuronal antibodies. RESULTS SNHL was detected in five CD patients (8.5%) and in two controls (3.4%). In one patient, the SNHL was bilateral, whereas the remaining four had a monolateral impairment. The prevalence of SNHL was not significantly different between CD patients and controls. At least one of the antibodies tested for was positive in two of the five CD patients with SNHL and in 12 of the 54 CD patients without SNHL. Antineuronal antibodies to central nervous system antigens were consistently negative in the five CD patients with SNHL. Only one of the five CD patients with SNHL had Hashimoto thyroiditis. CONCLUSIONS SNHL and CD occur coincidentally. Hearing function should be assessed only in CD patients with clinical signs of hearing deficiency.