The human leukocyte antigen DQ B1*02 is more frequent in patients with tissuetransglutaminase antibody levels ≥100 U/mL
A Mubarak1, E Spierings2, VM. Wolters1, RHJ Houwen1
Departments of Paediatric Gastroenterology (1) and Immunology (2), University Medical Center Utrecht,
The Netherlands
Patients with tissue-transglutaminase antibody (tTGA) levels ≥100 U/mL virtually always have
celiac disease (CD), whereas the disease can be histologically rejected in a significant number of
patients with lower tTGA levels. The aim of the current study was to evaluate whether CD
patients with tTGA ≥100 U/mL show a different genetic risk profile with regards to the disease
associated human leukocyte antigen (HLA) types than patients with tTGA <100 U/mL.
The study included all paediatric patients with biopsy confirmed CD (Marsh III) in whom HLA
typing was done between 2009 and 2011. HLA typing was performed using sequence-specific
oligonucleotide Primed PCR (PCR-SSO) typing. In all patients tTGA was measured by means of
ELISA using human recombinant tissue-transglutaminase as antigen. The distribution of HLA-DQ
2.5 (DQA1*05:01-DQB1*02:01), DQ 2.2 (DQA1*02:01, DQB1*02:02) and DQ 8 (DQA1*03:01DQB1*03:02) in patients with tTGA ≥100 U/mL and patients with lower levels of tTGA was
compared. P-values <0.05 were considered statistically significant.
Results: A total of 95 celiac children were included in the study of whom 68 patients had tTGA
≥100 U/mL. A total of 27 patients had tTGA levels <100 U/mL of whom in only 2 children the
antibody levels were <10 U/mL (negative).
Compared to the low tTGA group, in the tTGA ≥100 U/mL group a higher percentage of the
patients were homozygous for HLA-DQ 2.5 (23.5% versus 11.1%), although this difference was
not statistically significant. Similarly, more CD children in the high tTGA group (27.9%) were HLADQ 2.5/2.2 heterozygous as compared to the children with lower tTGA (14.8%), although again
this was not statistically significant. By contrast, when looking specifically at homozygosity for
HLA-DQ B1*02, the prevalence of patients carrying 2 copies of this molecule turned out to be
significantly (P-value 0.044) higher in the tTGA ≥100 U/mL group (48.5%) compared to the low
tTGA group (25.9%). Finally, no differences in prevalence were found for HLA-DQ 8 homozygosity
or heterozygosity for HLA-DQ8 in combination with either HLA-DQ 2.5 or DQ 2.2.
In Conclusion, patients with tTGA ≥100 U/mL have a different HLA risk profile compared to CD
patients with lower tTGA levels, as almost 50% of the high tTGA group carry 2 copies of the HLADQ B1*02 molecule while only around a quarter of the patients in the low tTGA group carries 2
copies. Pathofysiologically, increased abundance of the highly gluten affinitive HLA-DQ B1*02
molecule may be responsible for the enhanced antibody response.