Coeliac disease

Coeliac disease can present in different forms:

Classical form

Gastrointestinal symptoms such as chronic diarrhoea, abdominal pain, bloating, and malabsorption.

Non-classical form

Often without prominent gastrointestinal symptoms, manifestations may include iron deficiency anaemia, fatigue, osteoporosis, elevated liver enzymes, or neurological symptoms.

Silent form

No obvious symptoms despite typical immunological and histological findings.

In addition to intestinal manifestations, patients may develop extraintestinal features, including:

• Iron deficiency anemia
• Dermatitis herpetiformis
• Neurological symptoms (e.g. neuropathy, ataxia)
• Infertility or recurrent pregnancy loss
• Increased risk of other autoimmune diseases

Coeliac disease is one of the most common autoimmune disorders worldwide.

• The prevalence in Europe and North America is approximately 1% of the general population.
• Many affected individuals remain undiagnosed because symptoms may be mild, atypical, or absent.
• First-degree relatives of affected individuals have a substantially increased risk compared with the general population.
• Approximately 30–40% of Europeans carry HLA-DQ2 and/or HLA-DQ8, whereas only a minority will develop coeliac disease.

Coeliac disease is strongly linked to specific HLA class II molecules:

• HLA-DQ2 (approximately 90–95% of patients)
• HLA-DQ8 (most remaining cases)

These molecules are essential because they:

• Bind gluten-derived (gliadin) peptides
• Present them to CD4⁺ T cells
• Trigger the inflammatory immune response in the intestinal mucosa

The absence of both HLA-DQ2 and HLA-DQ8 makes celiac disease extremely unlikely, giving HLA testing an exceptionally high negative predictive value (>99%).

The diagnosis of coeliac disease is based on a combination of:

Serology

Examples include:

• Anti-tissue transglutaminase antibodies (tTG-IgA)
• Endomysial antibodies (EMA)

Histology

Duodenal biopsy demonstrating:

• Villous atrophy
• Increased intraepithelial lymphocytes
• Mucosal inflammation

In selected paediatric patients, diagnosis may be established without biopsy according to guideline-defined criteria.

Several disorders may mimic coeliac disease clinically, serologically, or histologically and should be considered when the diagnosis is uncertain:

• Non-coeliac gluten sensitivity
• Wheat allergy
• Irritable bowel syndrome (IBS)
• Inflammatory bowel disease (especially Crohn’s disease)
• Microscopic colitis
• Small intestinal bacterial overgrowth (SIBO)
• Lactose intolerance
• Giardiasis and other infectious enteropathies
• Autoimmune enteropathy
• Drug-induced enteropathy (e.g. olmesartan-associated enteropathy)

In patients with persistent symptoms despite a gluten-free diet, alternative diagnoses and other causes of malabsorption should be carefully evaluated.

Negative result (No HLA-DQ2 / DQ8 detected)

• Coeliac disease can be excluded with very high confidence.
• No further routine serological monitoring is usually required.

Positive result (HLA-DQ2 and/or DQ8 present)

• Indicates genetic susceptibility only.
• Does not confirm the disease.
• Approximately 30–40% of the general population carry these alleles without developing coeliac disease.

Therefore, HLA testing is particularly useful as a rule-out test and should not be used as a standalone diagnostic marker.

HLA typing helps to:

• Exclude coeliac disease reliably
• Avoid unnecessary follow-up testing
• Identify individuals who may benefit from long-term monitoring
• Support diagnostic decisions in complex or atypical cases

It represents an important complementary tool alongside serology and histology in a structured diagnostic workflow.

• Coeliac disease is a gluten-triggered autoimmune disorder with a strong HLA association.
• HLA-DQ2 and HLA-DQ8 account for nearly all genetic susceptibility to the disease.
• HLA typing has an exceptionally high negative predictive value.
• It is particularly useful for excluding the disease and guiding further diagnostic evaluation.

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