PMID- 23981538
OWN - NLM
STAT- MEDLINE
DCOM- 20150529
LR  - 20220331
IS  - 1741-7015 (Electronic)
IS  - 1741-7015 (Linking)
VI  - 11
DP  - 2013 Aug 28
TI  - A novel serogenetic approach determines the community prevalence of celiac 
      disease and informs improved diagnostic pathways.
PG  - 188
LID - 10.1186/1741-7015-11-188 [doi]
AB  - BACKGROUND: Changing perspectives on the natural history of celiac disease (CD), 
      new serology and genetic tests, and amended histological criteria for diagnosis 
      cast doubt on past prevalence estimates for CD. We set out to establish a more 
      accurate prevalence estimate for CD using a novel serogenetic approach. METHODS: 
      The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with 
      'biopsy-confirmed' CD, and in two age-stratified, randomly selected community 
      cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific 
      serology. RESULTS: Only five 'biopsy-confirmed' patients with CD did not possess 
      the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were 
      misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in 
      the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated 
      gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of 
      the community women and 6.9% and 6.9%, respectively, of the community men, but in 
      the screen-positive group, only 71% and 75%, respectively, of women and 65% and 
      63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was 
      possible for 41% of seropositive women and 50% of seropositive men, and led to 
      biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative 
      risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG 
      screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 
      1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts 
      indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and 
      further serology, could have reduced unnecessary gastroscopies due to 
      false-positive serology by at least 40% and by over 70%, respectively. 
      CONCLUSIONS: Screening with TG2 IgA serology and requiring biopsy confirmation 
      caused the community prevalence of CD to be substantially underestimated. Testing 
      for HLA-DQ genes and confirmatory serology could reduce the numbers of 
      unnecessary gastroscopies.
FAU - Anderson, Robert P
AU  - Anderson RP
FAU - Henry, Margaret J
AU  - Henry MJ
FAU - Taylor, Roberta
AU  - Taylor R
FAU - Duncan, Emma L
AU  - Duncan EL
FAU - Danoy, Patrick
AU  - Danoy P
FAU - Costa, Marylia J
AU  - Costa MJ
FAU - Addison, Kathryn
AU  - Addison K
FAU - Tye-Din, Jason A
AU  - Tye-Din JA
FAU - Kotowicz, Mark A
AU  - Kotowicz MA
FAU - Knight, Ross E
AU  - Knight RE
FAU - Pollock, Wendy
AU  - Pollock W
FAU - Nicholson, Geoffrey C
AU  - Nicholson GC
FAU - Toh, Ban-Hock
AU  - Toh BH
FAU - Brown, Matthew A
AU  - Brown MA
FAU - Pasco, Julie A
AU  - Pasco JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130828
PL  - England
TA  - BMC Med
JT  - BMC medicine
JID - 101190723
RN  - 0 (HLA-DQ Antigens)
RN  - EC 2.3.2.13 (Protein Glutamine gamma Glutamyltransferase 2)
RN  - EC 2.3.2.13 (Transglutaminases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Australia/epidemiology
MH  - Biopsy/methods
MH  - *Celiac Disease/diagnosis/epidemiology/genetics/immunology
MH  - Diagnostic Errors/*prevention & control
MH  - Female
MH  - *GTP-Binding Proteins/analysis/immunology
MH  - Genetic Testing/methods
MH  - HLA-DQ Antigens/*genetics
MH  - Humans
MH  - Intestines/*pathology
MH  - Male
MH  - Mass Screening/methods
MH  - Middle Aged
MH  - Predictive Value of Tests
MH  - Prevalence
MH  - Protein Glutamine gamma Glutamyltransferase 2
MH  - Serologic Tests/methods
MH  - *Transglutaminases/analysis/immunology
PMC - PMC3765645
EDAT- 2013/08/29 06:00
MHDA- 2015/05/30 06:00
PMCR- 2013/08/28
CRDT- 2013/08/29 06:00
PHST- 2013/05/08 00:00 [received]
PHST- 2013/08/02 00:00 [accepted]
PHST- 2013/08/29 06:00 [entrez]
PHST- 2013/08/29 06:00 [pubmed]
PHST- 2015/05/30 06:00 [medline]
PHST- 2013/08/28 00:00 [pmc-release]
AID - 1741-7015-11-188 [pii]
AID - 10.1186/1741-7015-11-188 [doi]
PST - epublish
SO  - BMC Med. 2013 Aug 28;11:188. doi: 10.1186/1741-7015-11-188.