J Clin Immunol (2013) 33:1027–1030 DOI 10.1007/s10875-013-9888-z
BRIEF COMMUNICATION
Antibodies to Deamidated Gliadin Peptides: An Accurate Predictor of Coeliac Disease in Infancy Sergio Amarri & Patrizia Alvisi & Roberto De Giorgio & Maria Carolina Gelli & Ronny Cicola & Francesco Tovoli & Romano Sassatelli & Giacomo Caio & Umberto Volta
Received: 4 January 2013 / Accepted: 18 March 2013 / Published online: 5 April 2013 # Springer Science+Business Media New York 2013
Abstract Immunoglobulin G antibodies against deamidated gliadin peptides are now known to have diagnostic accuracy comparable to tissue transglutaminase and endomysium autoantibodies in patients with coeliac disease. However, little is known about their predictive value in infants with a suspected gluten enteropathy. We tested whether deamidated gliadin immunoglobulin G antibodies are more reliable than traditional tests for coeliac disease screening in infancy. Sixty-five children under 2 years of age (42 with malabsorption, 23 controls) were tested for deamidated gliadin immunoglobulin G, tissue transglutaminase and endomysium immunoglobulin A, and gliadin immunoglobulins A and G . Thirty-seven of the 42 children with malabsorption had deamidated gliadin antibodies, associated with tissue transglutaminase and endomysial antibodies in 33, and with gliadin immunoglobulins A and G in 21 and 29, respectively. Intestinal biopsy was
S. Amarri Pediatric Unit, IRCCS - Arcispedale Santa Maria Nuova, Reggio Emilia, Italy P. Alvisi Pediatric Unit, Ospedale Maggiore, Bologna, Italy R. De Giorgio (*) : R. Cicola : F. Tovoli : G. Caio : U. Volta Department of Medical and Surgical Sciences/Digestive Diseases and Internal Medicine, Building #5, St. Orsola-Malpighi Hospital, Via Massarenti, 9, 40138 Bologna, Italy e-mail:
[email protected] M. C. Gelli Pathology Unit, IRCCS - Arcispedale Santa Maria Nuova, Reggio Emilia, Italy R. Sassatelli Digestive Endoscopy Unit, IRCCS - Arcispedale Santa Maria Nuova, Reggio Emilia, Italy
performed in 34 of the 37 children positive for deamidated gliadin antibodies. Thirty-two/34 showed villous atrophy consistent with coeliac disease, while the remaining two had a Marsh 1 and a normal mucosa, respectively. Only gliadin immunoglobulins A (4.3 %) and G (39.1 %) were found in controls. The sensitivity of deamidated gliadin, tissue transglutaminase and endomysial antibodies for coeliac disease was significantly higher than that of gliadin immunoglobulins G and A. High titre deamidated gliadin antibodies correlated with severe intestinal damage. Deamidated gliadin antibodies showed a higher diagnostic accuracy for coeliac disease than gliadin antibodies in infancy. High titre deamidated gliadin antibodies predict a severe gluten-dependent duodenal damage. Keywords Coeliac disease . diagnostic accuracy . gliadin peptides . intestinal malabsorption . serological diagnosis
Introduction Coeliac disease (CD) is an autoimmune small bowel disorder triggered by gluten in genetically susceptible individuals [1]. Although intestinal biopsy is still the diagnostic “gold standard”, the relevance of serology has recently increased [2]. Immunoglobulin A (IgA) antibodies against tissue transglutaminase (tTGA) and endomysium (EmA) are the best markers for CD. Deamidated gliadin peptide antibodies (DGP) have recently replaced the traditional antibodies against gliadin (AGA) [3–8]. The sensitivity of tTGA and EmA for CD is lower in infancy than in older children and adults [9, 10]. A higher sensitivity has been reported for AGA which, however, lack specificity [11]. In contrast, DGP may be more reliable than other tests to detect CD in infancy [12–15].
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J Clin Immunol (2013) 33:1027–1030
The present study was designed to verify whether DGP IgG perform better than other serological markers for CD diagnosis in infancy, and whether DGP titres correlate with the severity of intestinal damage.
Materials and Methods Patients Between November 2010 and January 2012 we have investigated two groups of infants under the age of 2 years: 1) group A, 42 non-consecutive children (27 females) with malabsorption characterized by chronic diarrhea, weight loss and failure to thrive [16]; 2) group B, 23 controls (13 females) with respiratory, neurological and/or infectious symptoms. The study protocol was approved by the Reggio Emilia Hospital Ethics Committee. Serum Antibody Tests All patients and controls underwent CD serology testing for DGP IgG, tTGA IgA and AGA IgG/IgA, detected by commercially available ELISAs (Eurospital, Trieste, Italy) and for EmA IgA, detected by indirect immunofluorescence (IFL) on human umbilical cord [15, 17]. Intestinal Biopsy Endoscopic intestinal biopsy was proposed to all antibody positive patients. Two biopsies from the bulb and two from the second duodenal portion were obtained and classified according to well-recognized criteria according
Fig. 1 Correlation between titres of IgG antibodies to deamidated gliadin peptides (DGP) and the severity of intestinal damage: a significant correlation was observed between high DGP titre and partial/ subtotal villous atrophy (lesion 3b-3c) (Mann–Whitney test, Z -2.466, P
