Abstract
HLA genotyping of DQ2 and DQ8 alleles has been eliminated from the diagnostic algorithm for Celiac Disease (CD) diagnosis in the currently published guidelines by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) in 2020. Our study, initiated prior to the publication of 2020 guidelines, evaluated the utility of HLA DQ2 and DQ8 genotyping in the cohort of 537 children with CD and their 1420 first degree relatives (FDRs). We attempted to evaluate its applicability in low middle-income countries like India. Prevalence of CD was observed at 18.52% and 15.68% based on serological and histopathological diagnosis in FDRs. HLA DQA1*0501 and DQB1*0201 alleles were the most frequent alleles observed in index cases (84.4% versus 86.4%), biopsy proven FDRs (77.9% vs 72.15) and serology negative FDRs (67.7% vs 58.3%) (p<0.001). A strong association of DQA1*0501 and DQA1*0301 alleles was observed with high serology positivity (p<0.05). The majority of the subjects in our cohort had histopathologic scores of 3c (54.80%), 3b (22.13%), 3a (22%) and grade 2 (1.05%) (p<0.001). HLA DQB1*0201 was observed as 100% in cases with Marsh grade 2, 72.5% in grade 3a, 82.7% in grade 3b and 85.6% in grade 3c (p=0.017) mucosal lesions. HLA DQA1*0501 and DQB1*0201 alleles of the DQ2 genotype also predicted the severity of intestinal mucosal damage assessed by Marsh grading when used in conjunction with anti tTG-IgA serology. When performed In-house using Polymerase Chain Reaction-Sequence Specific Primers (PCR-SSP) approach, the assay was economical and is still relevant in screening at-risk FDRs for an early diagnosis where In-house diagnostics are already in place.