title: Detection of celiac disease and lymphocytic enteropathy by parallel serology and histopathology in a population-based study.
abstract: OBJECTIVE
  Although serologic analysis is used in diagnosis of celiac disease, histopathology is considered most reliable. We performed a prospective study to determine the clinical, pathologic, and serologic spectrum of celiac disease in a general population (Kalixanda study).
  
  
  METHODS
  A random sample of an adult general population (n = 1000) was analyzed by upper endoscopy, duodenal biopsy, and serologic analysis of tissue transglutaminase (tTg) levels; endomysial antibody (EMA) levels were analyzed in samples that were tTg+. The cut off values for diagnosis of celiac disease were villous atrophy with 40 intraepithelial lymphocytes (IELs)/100 enterocytes (ECs).
  
  
  RESULTS
  Samples from 33 subjects were tTg+, and 16 were EMA+. Histologic analysis identified 7 of 1000 subjects (0.7%) with celiac disease; all were tTg+, and 6 of 7 were EMA+. Another 26 subjects were tTg+ (7/26 EMA+). This was addressed by a second quantitative pathology study (nested case control design) using a threshold of 25 IELS/100 ECs. In this analysis, all 13 samples that were tTg+ and EMA+ had > or =25 IELs/100 ECs. In total, 16 subjects (1.6%) had serologic and histologic evidence of gluten-sensitive enteropathy. IELs were quantified in duodenal biopsy samples from seronegative individuals (n = 500); 19 (3.8%) had >25 IELs and lymphocytic duodenosis.
  
  
  CONCLUSIONS
  Measurement of > or =25 IELs/100 ECs correlated with serologic indicators of celiac disease; a higher IEL threshold could miss 50% of cases. Quantification of tTg is a sensitive test for celiac disease; diagnosis can be confirmed by observation of > or =25 IELs/100ECs in duodenal biopsy specimens. Lymphocytic enteropathy (celiac disease and lymphocytic duodenosis) is common in the population (5.4%).
authors.affiliation: Department of Histopathology, Faculty of Medicine, St. Mary's Campus, Imperial College London, London, United Kingdom. mm.walker@imperial.ac.uk
authors.forename: Marjorie M
authors.initials: MM
authors.lastname: Walker
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Murray
authors.forename: Jukka
authors.initials: J
authors.lastname: Ronkainen
authors.forename: Pertti
authors.initials: P
authors.lastname: Aro
authors.forename: Tom
authors.initials: T
authors.lastname: Storskrubb
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amato
authors.forename: Brian
authors.initials: B
authors.lastname: Lahr
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Talley
authors.forename: Lars
authors.initials: L
authors.lastname: Agreus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002446:Celiac Disease / Q000175:diagnosis* / Q000473:pathology; D004386:Duodenum / Q000473:pathology; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012698:Serologic Tests
chemical_list: D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen
references.citation: Am J Gastroenterol. 2007 Jul;102(7):1454-60
references.pmid: 17355413
references.citation: Gut. 1995 Oct;37(4):519-23
references.pmid: 7489939
references.citation: Acta Paediatr Suppl. 1996 May;412:29-35
references.pmid: 8783752
references.citation: Am J Gastroenterol. 1994 Jun;89(6):843-6
references.pmid: 7864924
references.citation: Am J Gastroenterol. 1999 Apr;94(4):888-94
references.pmid: 10201452
references.citation: Best Pract Res Clin Gastroenterol. 2005 Jun;19(3):341-50
references.pmid: 15925840
references.citation: Clin Gastroenterol Hepatol. 2003 Jan;1(1):19-27
references.pmid: 15017513
references.citation: Scand J Gastroenterol. 2005 May;40(5):564-72
references.pmid: 16036509
references.citation: Pathologe. 2001 Jan;22(1):72-81
references.pmid: 11225448
references.citation: Gut. 2003 Jul;52(7):960-5
references.pmid: 12801951
references.citation: Scand J Prim Health Care. 2000 Jun;18(2):105-10
references.pmid: 10944065
references.citation: J Clin Pathol. 2002 May;55(5):393-4
references.pmid: 11986350
references.citation: J Clin Pathol. 2002 Jun;55(6):424-8
references.pmid: 12037023
references.citation: Immunogenetics. 2009 Apr;61(4):247-56
references.pmid: 19255754
references.citation: J Clin Gastroenterol. 2008 May-Jun;42(5):460-5
references.pmid: 18344893
references.citation: Am J Gastroenterol. 2003 Sep;98(9):2027-33
references.pmid: 14499783
references.citation: Aliment Pharmacol Ther. 2007 Nov 1;26(9):1217-25
references.pmid: 17944736
references.citation: Helicobacter. 2006 Aug;11(4):224-30
references.pmid: 16882324
references.citation: Arch Intern Med. 2003 Feb 10;163(3):286-92
references.pmid: 12578508
references.citation: Gastroenterology. 2009 Jul;137(1):88-93
references.pmid: 19362553
references.citation: Gut. 1991 Nov;32(11):1412-4
references.pmid: 1836446
references.citation: JAMA. 2005 May 18;293(19):2343-51
references.pmid: 15900004
references.citation: Eur J Pediatr. 1982 Oct;139(2):101-5
references.pmid: 6759132
references.citation: Mod Pathol. 2005 Aug;18(8):1134-44
references.pmid: 15803187
references.citation: Scand J Gastroenterol. 1998 Sep;33(9):944-9
references.pmid: 9759950
references.citation: Gastroenterology. 1992 Jan;102(1):330-54
references.pmid: 1727768
references.citation: Eur J Gastroenterol Hepatol. 1999 Oct;11(10):1185-94
references.pmid: 10524652
references.citation: Acta Gastroenterol Belg. 2005 Oct-Dec;68(4):419-23
references.pmid: 16432993
references.citation: Scand J Gastroenterol. 1997 Jan;32(1):48-51
references.pmid: 9018766
references.citation: Scand J Gastroenterol. 2004 Dec;39(12):1280-8
references.pmid: 15743007
references.citation: Neth J Med. 1998 Jul;53(1):15-9
references.pmid: 9718937
references.citation: Arch Pathol Lab Med. 2006 Jul;130(7):1020-5
references.pmid: 16831028
references.citation: Scand J Gastroenterol. 2004 Dec;39(12):1201-8
references.pmid: 15742996
references.citation: Gastroenterology. 2009 Mar;136(3):816-23
references.pmid: 19111551
references.citation: Q J Med. 1981 Autumn;50(200):435-49
references.pmid: 7342169
references.citation: Eur J Gastroenterol Hepatol. 2000 Mar;12(3):345-9
references.pmid: 10750656
references.citation: J Clin Pathol. 2005 Jun;58(6):573-4
references.pmid: 15917404
references.citation: Dig Dis Sci. 2004 Apr;49(4):546-50
references.pmid: 15185855
references.citation: Arch Dis Child. 1987 May;62(5):465-8
references.pmid: 3606178
references.citation: Scand J Gastroenterol. 2004 Feb;39(2):138-44
references.pmid: 15000275
references.citation: J Pediatr Gastroenterol Nutr. 1988 Jul-Aug;7(4):532-6
references.pmid: 3397844
references.citation: Gut. 1979 Jun;20(6):509-12
references.pmid: 572802
references.citation: J Pediatr Gastroenterol Nutr. 1988 Jul-Aug;7(4):537-43
references.pmid: 3294370
references.citation: J Clin Pathol. 2006 Oct;59(10):1008-16
references.pmid: 17021129
references.citation: Am J Gastroenterol. 2009 Jan;104(1):142-8
references.pmid: 19098862
references.citation: PLoS One. 2008 May 28;3(5):e2270
references.pmid: 18509540
references.citation: N Engl J Med. 2007 Oct 25;357(17):1731-43
references.pmid: 17960014
references.citation: Am J Clin Pathol. 2001 Jul;116(1):63-71
references.pmid: 11447753
references.citation: N Engl J Med. 2003 Jun 19;348(25):2517-24
references.pmid: 12815137
references.citation: Dig Liver Dis. 2008 Oct;40(10):809-13
references.pmid: 18467196
references.citation: J Pediatr. 1993 Aug;123(2):262-4
references.pmid: 8345423
references.citation: J Pediatr Gastroenterol Nutr. 1987 Sep-Oct;6(5):707-9
references.pmid: 3694364
references.citation: Am J Surg Pathol. 1996 Oct;20(10):1161-81
references.pmid: 8827022
references.citation: Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G217-25
references.pmid: 18006603
references.citation: J Pediatr Gastroenterol Nutr. 1995 Jul;21(1):64-8
references.pmid: 8576817
references.citation: Gut. 1986 Dec;27(12):1464-70
references.pmid: 3804022
references.citation: J Clin Pathol. 1987 Oct;40(10):1228-30
references.pmid: 3680547
references.citation: Clin Diagn Lab Immunol. 2000 Jul;7(4):584-7
references.pmid: 10882656
references.citation: Gastroenterology. 2005 Apr;128(4 Suppl 1):S57-67
references.pmid: 15825128
references.citation: Ann Med. 2008;40(3):223-31
references.pmid: 18382888
references.citation: Clin Gastroenterol Hepatol. 2008 Apr;6(4):426-32; quiz 370
references.pmid: 18304884