IYD Antibody
Description
Definition and Biological Role of IYD Antibody
The IYD antibody (H3 Ab) is a monoclonal antibody targeting iodotyrosine deiodinase (IYD), an enzyme responsible for scavenging iodide from monoiodotyrosine (MIT) and diiodotyrosine (DIT) during thyroid hormone synthesis . Unlike conventional antibodies that neutralize pathogens, H3 Ab uniquely acts as both an agonist and antagonist of IYD, enabling it to regulate thyroid hormone levels while inducing thermogenic cellular differentiation .
Key Functional Attributes:
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Antagonist action: Blocks IYD’s enzymatic activity, reducing thyroxine (T4) synthesis by 35–50% in murine models .
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Agonist action: Binds to IYD on stem cells, triggering differentiation into brown adipocyte-like cells and enhancing core body temperature by 1.2–1.5°C .
Mechanistic Insights from In Vivo Studies
Recent experiments in C57BL/6J mice revealed the antibody’s dual functionality:
| Parameter | H3 Ab Treatment | Control |
|---|---|---|
| Serum T4 levels | 3.2 ± 0.4 µg/dL | 6.1 ± 0.5 µg/dL |
| Body weight gain | 12% reduction | No significant change |
| Core body temperature | 37.9 ± 0.3°C | 36.7 ± 0.2°C |
Mechanism Breakdown:
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Thyroid gland: H3 Ab inhibits IYD’s iodide-recycling function, increasing MIT/DIT substrates and reducing T4 production (antagonist effect) .
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Stem cells: Binds to IYD-expressing stem cells, activating differentiation into brown adipocytes via undefined signaling pathways (agonist effect) .
Metabolic Disease Management
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Hypothyroidism: By reducing T4 synthesis, H3 Ab could serve as an adjunct therapy for hyperthyroidism or thyroid hormone resistance syndromes .
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Obesity: Brown adipocyte differentiation enhances thermogenesis, potentially increasing energy expenditure by 15–20% in preclinical models .
Limitations and Future Directions
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No significant impact on blood glucose levels was observed despite increased thermogenesis .
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The exact signaling mechanism linking IYD binding to adipocyte differentiation remains unresolved .
Comparative Analysis with Conventional Antibodies
While most antibodies neutralize antigens or recruit immune effectors , H3 Ab’s dual functionality is unprecedented:
Research Challenges and Validation
Product Specs
Target Background
- The rate-limiting processes that contribute to the ability of flavin to promote reductive dehalogenation in human IYD. PMID: 26151430
- A switch between one- and two-electron chemistry of iodotyrosine deiodinase is controlled by substrate. PMID: 25395621
- Iodotyrosine deiodinase defect identified via genome-wide approach. PMID: 22535972
- High activity of human saliva peroxidase with iodide as a substrate may play a crucial role in the bioavailability and metabolism of biologically active iodide. PMID: 21870604
- Mutations in DEHAL1 leads to hypothyroidism, goiter and mental retardation (Review) PMID: 20298747
- Molecular cloning and investigation of the localization and activity of DEHAL1 PMID: 15289438
- The cytoplasmic tail of DEHAL1 could play a role in the stability of the protein PMID: 16910871
- Diffuse cytoplasmic localization or downregulation of DEHAL1 expression in thyroid cancers suggests alteration or loss of DEHAL1 function during thyroid cell dedifferentiation. PMID: 17322488
- Homozygous mutations in DEHAL1 appear to cause human iodotyrosine deiodinase deficiency, leading to hereditary hypothyroidism and goiter PMID: 18434651
- This study describes a functional mutation within IYD, demonstrating the molecular basis of the iodine wasting form of congenital hypothyroidism PMID: 18765512
