Anti-transglutaminase 2 antibodies are most specific for which disease?

• A. Celiac disease
• B. Systemic lupus erythematosus
• C. Rheumatoid arthritis
• D. Multiple sclerosis

Answer: (A)

Anti-transglutaminase 2 antibodies are most strongly associated with celiac disease. Tissue transglutaminase 2 is the autoantigen targeted in the disease, and the immune response to gluten drives the production of these antibodies. Their presence in serum correlates with the characteristic intestinal damage seen in celiac disease and they tend to disappear when a gluten-free diet is followed. This makes the antibody highly specific for celiac disease compared with other autoimmune conditions like systemic lupus erythematosus, rheumatoid arthritis, or multiple sclerosis, where this antibody is not typically found. In screening, a positive IgA anti-tTG test strongly supports a celiac diagnosis (with biopsy often used to confirm), and alternatives exist if IgA deficiency is present.