autoantibodies celiac
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The immune system filing suit against its own proteins — autoantibodies are both a driver of tissue damage and the primary evidence used for diagnosis.
An autoantibody is an antibody directed against one of the body's own proteins. Their presence indicates the immune system has crossed the line from responding to a foreign threat (gluten) into attacking self-tissue. In celiac disease, the formation of autoantibodies is a direct consequence of tTG transamidating gliadin to itself, creating novel targets the immune system then attacks.
The Key Autoantibody: Anti-tTG IgA
Anti-tissue transglutaminase IgA (TTG IgA) — the central autoantibody in celiac:
- Produced when B cells respond to tTG–gliadin complexes formed by transamidation
- Detected in blood by the TTG IgA test
- Rises with active gluten consumption and falls on a gluten-free-diet
- Severity of villous-atrophy correlates with antibody levels
- Also deposits in the gut wall and other tissues, contributing directly to damage
Other Autoantibodies
| Autoantibody | Target | Clinical Use |
|---|---|---|
| Endomysial antibody (EMA IgA) | Connective tissue around smooth muscle (contains tTG) | Confirmatory test; ~100% specific but less sensitive |
| DGP IgG | Deamidated gliadin peptide | Used when IgA deficiency makes TTG IgA unreliable |
| TTG IgG | tTG | Backup when IgA-deficient; less accurate |
| AGA (antigliadin IgA/IgG) | Gliadin itself | Deprecated; superseded by more accurate tests |
| ARA (antireticulin) | Reticulin | Deprecated |
Why Autoantibodies Cause Extraintestinal Disease
tissue-transglutaminase is expressed in many tissues outside the gut: liver, bone, brain, heart, and skin. Anti-tTG antibodies circulate in the bloodstream and can deposit wherever tTG is expressed:
- Liver → celiac hepatitis (elevated transaminases)
- Bone → bone metabolism disruption
- Skin → dermatitis-herpetiformis (IgA deposits in skin)
- Brain/nerves → peripheral neuropathy, gluten-ataxia
This systemic reach is why celiac is considered an autoimmune disease, not just a food intolerance.
IgA Deficiency: A Diagnostic Trap
IgA deficiency is ~13× more common in celiac patients. If a patient has IgA deficiency, all IgA-based autoantibody tests (TTG IgA, EMA IgA) will be falsely negative — this is the most common source of missed diagnoses in celiac serology workups.
Related Concepts
tissue-transglutaminase | ttg-iga-test | iga-and-iga-deficiency | deamidation | dermatitis-herpetiformis | celiac-hepatitis | osteoporosis-celiac