Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma.
OBJECTIVE
Celiac disease (CD) is a common gluten-sensitive enteropathy associated with human leukocyte antigen (HLA)-DQ2 and HLA-DQ8. The aim of this study was to determine if a particular HLA-DQ subtype predisposes to complications such as refractory CD with (RCD II) or without aberrant T cells (RCD I), and enteropathy-associated T-cell lymphomas (EATL).


METHODS
Molecular HLA-DQ typing was performed on 43 RCD I, 43 RCD II, and 30 EATL patients, and compared with age-matched groups of 121 patients with histologically defined uncomplicated CD and 183 healthy controls. All individuals were Dutch Caucasians and were at least 21 years of age.


RESULTS
HLA-DQ2 was present in 79% of RCD I, 97.7% of RCD II, and 96.6% of EATL patients. The differences were significant when compared with 28.9% in controls but not with 91.7% in uncomplicated CD. Homozygosity for HLA-DQ2 was observed in 25.5% of RCD I, 44.1% of RCD II, and 53.3% of EATL patients vs 20.7% of uncomplicated CD patients and 2.1% of controls. HLA-DQ8 was present in 10.7% of CD, 16.2% of RCD I, 9.3% of RCD II, and 6.6% of EATL patients vs 20.2% of controls.


CONCLUSIONS
Homozygosity for HLA-DQ2 is associated with RCD II and EATL. Early identification of HLA-DQ2 homozygous CD patients may help to recognize CD patients at risk for developing these severe complications.
Al-Toma
Abdulbaqi
A
Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.
Goerres
Marije S
MS
Meijer
Jos W R
JW
Peña
A Salvador
AS
Crusius
J Bart A
JB
Mulder
Chris J J
CJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
D015703:Antigens, CD; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D011948:Receptors, Antigen, T-Cell