Function:

Glutamic Acid Decarboxylase (GAD) a neuronal protein is an enzyme responsible for the conversion of the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter g-aminobutyric acid (GABA). GAD is also expressed by pancreatic beta cells.

Antibodies Appear:

- Battan disease [6]

- Celiac disease [3]

- Cerebellar ataxia [4]

- Gluten sensitivity [3]

- Polyendocrine autoimmune syndrome [2]

- Stiff-person syndrome [2]

- Type 1 Diabetes [2, 4, 7]

Known Cross-Reactions:

- Casein; [1]

- Coxsackievirus; [5]

- Gliadin; [7]

- Rotavirus; [9]

- Cytomegalovirus; [10, 11]

- Rubella; [12]

- Buckwheat, Amaranth, Rice, Corn, Yeast, Potato, Quinoa, Oats [13]

Clinical Significance:

This enzyme is the major auto-antigen in Type I Diabetes. Researchers speculate that as a target antigen, GAD65 may directly, or indirectly, produce the T cell response cascade that results in insulin-dependent (type 1) diabetes mellitus. [7]

In addition to patients with autoimmunity against islet cell antigen (Type I Diabetes), patients with neurological disorders (low GABA) may also produce high levels of antibodies against GAD. [2, 4, 6]

Anti-GAD autoantibodies may result in an excess of excitatory neurotransmitters, which can lead to seizures. [5]

Due to cross-reactivity between gliadin and casein, [1] patients with antibodies against GAD65 should implement a dairy-free diet.

Additionally, in a study of Celiac patients, [3] 60% of the participants with Celiac disease produced GAD65, which may explain the relationship between Celiac disease and type-1 diabetes.

References:

1. Banchuin, et al. Cell-mediated immune responses to GAD and beta-casein in type 1 diabetes mellitus in Thailand. Diabetes Res Clin Pract, 2002; 55(3):237-245.

2. Ellis and Atkinson. The clinical significance of an autoimmune response against glutamic acid decarboxylase. Nat Med, 1996; 2:148-153.

3. Hadjivassiliou et al. Gluten sensitivity: from gut to brain. Lancet Neurol, 2010; 9:318-330.

4. Honnorat, et al. Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies. Arch Neurol, 2001; 58:225-230.

5. LeRoth, et al (eds.). Diabetes Mellitus (3rd ed.). Lippincott Williams & Wilkins: Philadelphia, PA; 2004.

6. Pearce, et al. Glutamic acid decarboxylase autoimmunity in Batten disease and other disorders. Neurology, 2004; 63:2001-2005.

7. Vojdani and Tarash. Cross-reaction between gliadin and different food and tissue antigens, Food Nutri Sci, 2013; 4:20-32.

8. Wilson, et al. Therapeutic alteration of insulin-dependent diabetes mellitus progression by T cell tolerance to glutamic acid decarboxylase 65 peptides in vitro and in vivo1. J Immunol, 2001; 167:569-577.

9. Honeyman, et al. Evidence for molecular mimicry between human T cell epitopes in rotavirus and pancreatic islet autoantigens. J Immunol, 2010; 184(4):2204-2210.

10. Hiemstra, et al. Cytomegalovirus in autoimmunity: T cell crossreactivity to viral antigen and autoantigen glutamic acid decarboxylase. Proc Natl Acad Sci U S A, 2001; 98(7):3988-3991.

11. Roep, et al. Molecular mimicry in type 1 diabetes: immune cross-reactivity between islet autoantigen and human cytomegalovirus but not Coxsackie virus. Ann N Y Acad Sci, 2002; 958:163-165.

12. Ou, et al. Cross-reactive rubella virus and glutamic acid decarboxylase (65 and 67) protein determinants recognised by T cells of patients with type I diabetes mellitus. Diabetologia, 2000; 43(6):750-762.

13. Kharrazian, et al. Detection of islet cell immune reactivity with low glycemic index foods: is this a concern for type 1 diabetes? J Diabetes Res, 2017; 2017:4124967.