GAD5 Antibody

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Description

Definition and Biological Role

GAD65 antibodies are autoantibodies directed against glutamic acid decarboxylase 65 (GAD65), an enzyme critical for synthesizing gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system. These antibodies disrupt GABA production, leading to neuronal hyperexcitability and associated neurological or endocrine disorders .

Clinical Syndromes Associated with GAD65 Antibodies

GAD65 antibodies are implicated in both neurological and autoimmune endocrine disorders:

ConditionKey FeaturesAntibody Titer RangeSources
Stiff-person syndrome (SPS)Progressive rigidity, spasms, hyperreflexia≥20 nmol/L (RIA) or >10,000 IU/mL (ELISA)
Cerebellar ataxiaGait imbalance, dysmetria, nystagmusHigh serum/CSF titers
Limbic encephalitisMemory deficits, seizures, psychiatric symptomsVariable, often elevated
Type 1 diabetes mellitusAutoimmune destruction of pancreatic β-cells<20 nmol/L (RIA) or <2,000 IU/mL (ELISA)
EpilepsyFocal impaired awareness seizures, status epilepticusTiters >50 U/mL (ELISA)

Key Assays:

  • Radioimmunoassay (RIA):

    • Threshold for neurological disorders: ≥20 nmol/L .

    • Distinguishes SPS (93% positivity) from diabetes .

  • ELISA:

    • High specificity for neurological disease at >10,000 IU/mL .

    • Low titers (5–2,000 IU/mL) correlate with diabetes or nonspecific autoimmunity .

Cerebrospinal Fluid (CSF) Analysis:

  • Intrathecal antibody synthesis supports neurological diagnoses .

  • CSF titers >5 U/mL indicate CNS involvement .

Pathogenic Mechanisms

  • GABAergic Dysfunction:
    Antibodies inhibit GAD65, reducing GABA synthesis and causing unchecked neuronal excitation .

  • T-cell Involvement:

    • Type 2 helper T cells (IL-4, IL-6) dominate in SPS, suppressing cytotoxic responses .

    • CD4+ T cells drive encephalomyelitis in animal models .

  • Epitope Specificity:
    Neurological disorders target linear N-terminal GAD65 epitopes, while diabetes antibodies bind conformational C-terminal domains .

Immunotherapy Responses:

TherapyEfficacy in SPSEfficacy in Epilepsy/EncephalitisSources
Intravenous immunoglobulin (IVIg)70–80% improvementPartial response (43%)
RituximabLimited benefitNo significant effect
CorticosteroidsModerate responseTransient titer reduction

Symptomatic Management:

  • GABA-enhancing drugs (e.g., benzodiazepines) provide partial relief .

Research Gaps and Future Directions

  • Titer-Disease Correlation: No linear relationship between antibody levels and clinical severity .

  • Pathogenicity Debate: Uncertain if antibodies directly cause disease or are secondary markers .

  • Therapeutic Targets: Need for controlled trials on B-cell depletion and cytokine modulation .

Product Specs

Buffer
Preservative: 0.03% ProClin 300. Constituents: 50% Glycerol, 0.01M Phosphate Buffered Saline (PBS), pH 7.4.
Form
Liquid
Lead Time
14-16 week lead time (made-to-order)
Synonyms
GAD5 antibody; At3g17760 antibody; MIG5.6 antibody; Glutamate decarboxylase 5 antibody; GAD 5 antibody; EC 4.1.1.15 antibody
Target Names
GAD5
Uniprot No.

Target Background

Function
This antibody targets glutamate decarboxylase 5 (GAD5), an enzyme that catalyzes the production of gamma-aminobutyric acid (GABA). Its calmodulin binding is calcium-dependent, suggesting a potential mechanism for calcium-regulated control of GABA biosynthesis, either directly or indirectly.
Database Links

KEGG: ath:AT3G17760

STRING: 3702.AT3G17760.1

UniGene: At.38660

Protein Families
Group II decarboxylase family
Tissue Specificity
Expressed in flowers.

Q&A

Given the context of "GAD5 Antibody" and focusing on academic research scenarios, here is a collection of FAQs tailored to meet the requirements:

Answer:

When designing experiments to study GAD5 antibodies, researchers should consider the following steps:

  • Selection of Study Population: Include both patients with autoimmune diseases (e.g., type 1 diabetes) and healthy controls to compare antibody prevalence and titers.

  • Antibody Detection Methods: Use sensitive assays like ELISA or proximity ligation assays to detect GAD5 antibodies in serum or cerebrospinal fluid.

  • Data Analysis: Perform statistical analysis to correlate antibody presence with disease progression or clinical outcomes.

Answer:

To resolve data contradictions, researchers should:

Answer:

Advanced research questions might include:

  • Mechanism of Action: Investigate how GAD5 antibodies interact with their target antigens and influence immune cell function.

  • Epitope Mapping: Identify specific epitopes recognized by GAD5 antibodies to understand their pathogenic potential.

  • Therapeutic Targeting: Explore whether neutralizing GAD5 antibodies could be a therapeutic strategy for autoimmune diseases.

Answer:

GAD5 antibodies can aid in:

  • Diagnosis: Serve as markers for early detection of autoimmune diseases, helping differentiate between conditions like type 1 and type 2 diabetes.

  • Treatment Monitoring: Monitor disease progression and response to therapies by tracking changes in antibody titers.

  • Therapeutic Strategies: Investigate immunotherapies aimed at reducing antibody production or blocking their effects.

Answer:

When developing assays for GAD5 antibodies, consider:

  • Sensitivity and Specificity: Optimize assays for high sensitivity and specificity to accurately detect antibodies in various samples.

  • Standardization: Standardize protocols across different laboratories to ensure comparable results.

  • Quality Control: Implement rigorous quality control measures to minimize false positives or negatives.

Answer:

The presence of GAD5 antibodies in non-diabetic individuals may indicate:

  • Subclinical Autoimmunity: Potential for future autoimmune disease development.

  • False Positives: Weak or transient antibody presence might not be clinically significant.

  • Population Studies: Conduct large-scale epidemiological studies to understand the prevalence and implications of these antibodies in healthy populations.

Example Data Table: GAD5 Antibody Prevalence in Different Populations

PopulationGAD5 Antibody Prevalence (%)
Type 1 Diabetes Patients70-80%
Type 2 Diabetes Patients5-10%
Non-Diabetic Individuals0.7-4.8%
Autoimmune Disease Patients (e.g., SLE)Variable, depending on disease

This table illustrates the varying prevalence of GAD5 antibodies across different populations, highlighting their potential as diagnostic markers.

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