تقييم الأنماط الجينية HLA-DQ2 / DQ8 في المرضى الذين يعانون من مرض حساسية القمح وارتباطها بالأجسام المضادة للأنسجة ترانسكلوتامنيز والأجسام المضادة للكليادين

Evaluation of HLA-DQ2 and DQ8 haplotypes in patients with Celiac Disease Correlation with Circulating Anti-Tissue Transglutaminase and Anti- Gliadin Antibodies

Abstract

The diagnosis of celiac disease (CD) remains one of the major challenges encountered with understanding the disease epidemiology, pathophysiology, management and development of therapeutic interventions. The atypical nature of majority of its symptoms coupled with late presentation of symptoms in early onset of disease among children and individuals with subclinical CD has been identified as the major culprits. While histological analysis of duodenal biopsy has been shown to have in capabilities of effectively diagnosing CD during early onset of disease in children due to absence of duodenal lesions, serological measurements of CD associated autoantibodies are useless in cases of seronegative patients with duodenal lesions or those with subclinical CD.
Genetic testing for the detection of HLADQ2 and HLA-DQ8 in patients suspected to have CD is gaining acceptance as a more effective method of CD diagnosis. The present study aimed to analyze the effectiveness of HLA-DQ genotyping of CD patients in predicting outcome of histologic and serological evaluations. The study recruited 90 patients clinically diagnosed as having CD and assessed their biodemographical characteristics of CD patients, their distribution with respect to histological analysis of duodenal biopsy, serological analysis of CD autoantibodies as well as presence of HLA-DQ2 and HLA-DQ8 haplotypes and their prediction of histological and serological profile of the patients. The results obtained indicated a female predominance of CD.
Genetic testing revealed that majority of the patients (77.8%) were HLA-DQ2 homozygotes while histologic analysis showed that 49 out of 90 patients had Marsh III grading of duodenal lesion with 25 patients having Marsh II. Seropositivity to anti-tissue glutaminase (tTG) IgA antibody was 41.1% with 63% of patients positive for anti-gliadin IgG antibody. Age-associated high antibody titer levels were observed in patients aged 33 – 39 years (390.04±67.21 U/mL) and 26 -32 years (352.62±50.12 U/mL) for anti-tTG IgA while 26-32 years (257.40±49.73 U/mL), 40 -47 years (220.04±24.35 U/mL) and then 33 – 39 years (214.55±32.40 U/mL) for anti-gliadin IgG. The prevalence of patients with HLA-DQ2 and HLA-DQ8 genotype was 100% as the predominant HLA-DQ2 predicted Marsh II outcome by 100%, Marsh III by 75%, anti-tTG IgA by 67.8%, anti-tTG IgG by 77.8%, anti-gliadin IgA by 82.9% and anti-gliadin IgG by 86%. These findings reinforce the assertion of the effectiveness of HLA-DQ genotyping CD diagnosis and recommends that genetic testing should be utilized on patients suspected to have CD since negative or positive results would rule out CD or prevent mal-diagnosis in patients with subclinical CD respectively.