Brief Article
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World J Gastroenterol. Nov 7, 2013; 19(41): 7114-7120
Published online Nov 7, 2013. doi: 10.3748/wjg.v19.i41.7114
Children with celiac disease and high tTGA are genetically and phenotypically different
Amani Mubarak, Eric Spierings, Victorien M Wolters, Henny G Otten, Fiebo JW ten Kate, Roderick HJ Houwen
Amani Mubarak, Victorien M Wolters, Roderick HJ Houwen, Department of Pediatric Gastroenterology, University Medical Center Utrecht, Wilhelmina Children’s Hospital, 3508 AB Utrecht, The Netherlands
Eric Spierings, Henny G Otten, Department of Immunology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
Fiebo JW ten Kate, Department of Pathology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
Author contributions: Mubarak A designed research, performed research, analyzed data and wrote the paper; Spierings E and Otten HG contributed new reagents or analytic tools; Wolters VM and ten Kate FJW performed research; Houwen RHJ designed and supervised research, supervised the writing of the paper.
Correspondence to: Amani Mubarak, MD, Department of Pediatric Gastroenterology, University Medical Center Utrecht, Wilhelmina Children’s Hospital, PO BOX 85090, 3508 AB Utrecht, The Netherlands. a.mubarak@umcutrecht.nl
Telephone: +31-88-7555555 Fax: +31-88-7555347
Received: January 21, 2013
Revised: June 18, 2013
Accepted: July 4, 2013
Published online: November 7, 2013
Processing time: 299 Days and 11.3 Hours
Abstract

AIM: To investigate whether celiac disease (CD) patients with tissue-transglutaminase antibody (tTGA) ≥ 100 U/mL are different from patients with lower tTGA levels.

METHODS: Biopsy-proven (Marsh III) pediatric CD patients (n = 116) were prospectively included between March 2009 and October 2012. The biopsies were evaluated by a single pathologist who was blinded to all of the patients’ clinical data. The patients were distributed into 2 groups according to their tTGA level, which was measured using enzyme-linked immunoassay: tTGA ≥ 100 U/mL and tTGA < 100 U/mL. The patients’characteristics, symptoms, human leukocyte antigen (HLA) genotype and degree of histological involvement were compared between the 2 groups.

RESULTS: A total of 34 (29.3%) children had tTGA values < 100 U/mL and 82 (70.7%) tTGA levels of ≥ 100 U/mL. Patients with high tTGA levels had lower average body weight-for-height standard deviation scores (SDS) than did patients with tTGA < 100 U/mL (-0.20 ± 1.19 SDS vs 0.23 ± 1.03 SDS, P = 0.025). In the low tTGA group, gastrointestinal symptoms were more common (97.1% vs 75.6%, P = 0.006). More specifically, abdominal pain (76.5% vs 51.2%; P = 0.012) and nausea (17.6% vs 3.7%, P = 0.018) were more frequent among patients with low tTGA. In contrast, patients with solely extraintestinal manifestations were only present in the high tTGA group (18.3%, P = 0.005). These patients more commonly presented with aphthous stomatitis (15.9% vs 0.0%, P = 0.010) and anemia (32.9% vs 11.8%, P = 0.019). In addition, when evaluating the number of CD-associated HLA-DQ heterodimers (HLA-DQ2.5, HLA-DQ2.2 and HLA-DQ8), patients with low tTGA levels more commonly had only 1 disease-associated heterodimer (61.8% vs 31.7%, P = 0.005), while patients with high tTGA more commonly had multiple heterodimers. Finally, patients with tTGA ≥ 100 U/mL more often had a Marsh IIIc lesion (73.2% vs 20.6%, P < 0.001) while in patients with low tTGA patchy lesions were more common (42.4% vs 6.8%, P < 0.001).

CONCLUSION: Patients with tTGA ≥ 100 U/mL show several signs of more advanced disease. They also carry a larger number of CD associated HLA-DQ heterodimers.

Keywords: Celiac disease; Serology; Anti-tissue transglutaminase antibodies; Human leukocyte antigen; Phenotype

Core tip: We prospectively investigated the differences between celiac disease (CD) (Marsh III) patients with tissue-transglutaminase antibody (tTGA) levels ≥ 100 U/mL and patients with lower tTGA levels. We found that patients with high tTGA more often carried multiple CD-associated heterodimers compared with patients with tTGA < 100 U/mL. In addition, high-tTGA patients have more advanced mucosal lesions that are also less patchy. Phenotypically, high-tTGA patients have a lower body weight and more often present with extraintestinal symptoms compared with patients with lower levels of tTGA, who more often have intestinal symptoms. These results provide further evidence that patients with tTGA ≥ 100 U/mL are truly a distinct group with more advanced disease.