Diagnostic accuracy of anti-gliadin antibodies in Non-Celiac Gluten Sensitivity (NCGS) patients
Introduction
Gluten is, by literature, a target of several diseases such as wheat allergy (WA), celiac disease (CD) and non-celiac gluten sensitivity (NCGS) [1], [2].
NCGS is a new clinical condition characterized by intestinal (diarrhea, abdominal pain, bloating and flatulence) and extra-intestinal symptoms (such as headache, lethargy, attention-deficit, hyperactivity disorder, recurrent oral ulceration), with an early onset after gluten ingestion, a rapid relief on a gluten free diet and an immediate relapse after the gluten challenge, related to immunological mechanisms still objects of several studies. The symptoms are not distinguishable from those of CD and WA [3], [4], [5], [6], [7].
NCGS epidemiological data are scarce: Sapone et al. [8] reported a 6% prevalence in a population of patients referred to Maryland Gastroenterology Clinics; these data could overestimate the real prevalence of the disease having been recorded in a referral center.
Biesiekierski et al. demonstrated, through a double blind study, that 30–40% of patients with inflammatory bowel disease diagnosed by Rome III criteria are NCGS patients [6].
A recent paper reported a possible prevalence of NCGS of 0.55% in the general population in the United States [9].
The diagnosis of NCGS is very difficult to date because of the lack of serological markers and specific clinical diagnostic criteria, so that NCGS diagnosis can be reached only by excluding CD and WA, and based on the direct association between gluten ingestion and symptoms onset [8], [10], [11], [12]. The optimal diagnostic algorithm necessary to define the patient with NCGS is still under debate [13].
Recent studies demonstrated that a large part of NCGS patients have HLA typing and antibodies related to CD, mainly antigliadin antibodies IgG [14], [15], [16], [17], [18], [19] (Table 1).
The aim of the study was to estimate AGA distribution and prevalence in NCGS population trying to identify a serological pattern to help the diagnosis and/or to mark the NCGS disease.
A cutoff for AGA IgA and AGA IgG on NCGS patients, and not on CD population, was set up for better discriminating NCGS patients.
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Patients
The study population included 59 patients attending the Referral Centre for Celiac Disease, Allergy and Clinical Immunology Unit, San Giovanni di Dio Hospital (Florence, Italy) between June 2011 and June 2012.
Of the 59 NCGS patients 40 were females (67.8%), with a female to male ratio of 2.1 to 1; the mean age was 45 ± 7.3. These patients experienced both intestinal and extraintestinal symptoms after gluten ingestion, including abdominal pain, bowel abnormalities (either diarrhea or
DBPCFC
Food challenge determines if an individual is in fact reactive to food. The double-blind, placebo-controlled food challenge (DBPCFC) is used for accurately diagnosing food allergies and for examining a wide variety of food related complaints. In this test, neither the physician nor the patient knows what the patient is being fed. For stopping an oral food challenge and declaring a challenge as positive or negative, symptoms should be objective and/or repetitive [31].
Data analysis
Data analysis was performed by the software STATGRAPHICS XVI (StatPoint Technologies, Warrenton, VA). Receiver operating characteristic (ROC) analysis was carried out using the software MedCalc 14.8.1 (MedCalc software bvba, Ostend, Belgium).
Distribution fitting
For each marker, data distribution was studied by standard skewness in order to verify the symmetry, then Gaussian distribution was verified by the Shapiro–Wilk W test. When Gaussian hypothesis was rejected we looked for the optimal distribution evaluating
Results
Distribution of AGA IgA and IgG were compared in CD, HI and NCGS patients in order to identify a potential serological marker that could be helpful for NCGS diagnosis. At the manufacturer's cutoff AGA IgG antibodies were detected in 6/59 (10.2%) of NCGS population, in 56/90 (62.2%) of CD, and in 2/70 (2.9%) of HI. AGA IgA antibodies were present in 4/59 (6.8%) of NCGS, with respect to the 63/90 (70%) of CD patients and 0/70 assayed in HI control group. Furthermore, in the NCGS group only 3
Discussion
NCGS has already been considered as a clinical entity after the increasing percentage of patients suffering from wheat sensitivity, complaining gastrointestinal and extraintestinal symptoms without meeting CD diagnostic criteria [33], [34], [35], [36], [37], [38]. Nowadays, since specific biomarkers for NCGS have not been identified yet, the diagnosis is mainly an exclusion diagnosis based on clinical and histological findings.
Recent literature data showed that the difference between AGA IgG
Conclusion
The correlation between AGA IgG and NCGS condition turned out to be slightly statistically significant. AGA IgG doesn't seem to be an adequately strong marker for its low statistically significance and for its lacking diagnostic accuracy; however it can partly help the NCGS diagnosis, integrated in the overall management of the patient.
Future researches are mandatory to identify reliable biomarkers for NCGS diagnosis and to better define the clinical and serological characteristics of NCGS
Conflicts of interest
S.Catani and S.Ugolini are employees of Eurospital (Trieste, Italy). The other authors declare that they have no conflict of interest.
Acknowledgments
We gratefully acknowledge the technical assistance of R. Bambi, G. Ciotta, F. Priami, F. Soldaini, C. Taddei, and M. Valentini. We would like to thank Eurospital (Trieste, Italy) for the assistance and the immunoassay kits gifted.
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