HLA-DQ2 Heterozygosity in Symptomatic Adults from Balochistan: A Case Series Supporting Coeliac Disease Diagnosis

Abstract

Background: Coeliac disease (CD) is an immune-mediated enteropathy triggered by gluten ingestion in genetically susceptible individuals. The presence of HLA-DQ2 and/or HLA-DQ8 haplotypes is a major genetic predisposing factor, with HLA-DQ2.5 showing the strongest association. In Pakistan, particularly in resource-limited regions such as Balochistan, CD remains underdiagnosed due to limited access to genetic testing and awareness of its clinical spectrum.

Objective: This case series aims to describe the clinical and genetic findings of three adult patients from Balochistan presenting with symptoms suggestive of coeliac disease, confirmed by the presence of HLA-DQ2 heterozygosity through whole blood genotyping.

Methods: Whole blood samples were collected from three symptomatic adults with chronic gastrointestinal complaints and malabsorptive features. HLA-DQA1 and HLA-DQB1 alleles were analyzed using standard genotyping techniques to determine the presence of HLA-DQ2 and HLA-DQ8 haplotypes. The allelic combinations were assessed to identify high-risk variants, particularly the DQ2.5 heterodimer.

Results: All three patients demonstrated heterozygous HLA-DQ2 haplotypes. One individual was identified as carrying the high-risk DQ2.5 combination (DQA105 and DQB102 alleles). Clinical features—including chronic diarrhea, weight loss, anemia, and fatigue—were consistent with coeliac disease in all cases. Symptomatic improvement was noted following the initiation of a gluten-free diet, further supporting the diagnosis.

Conclusion: This case series provides molecular evidence of HLA-DQ2 heterozygosity among symptomatic adults in Balochistan and reinforces the diagnostic relevance of HLA genotyping in suspected coeliac disease. Expanding access to genetic testing and increasing clinical awareness can enhance early detection and management of CD in underserved populations. Early identification of genetically at-risk individuals may significantly improve patient outcomes through timely dietary interventions and prevention of long-term complications.