sre-6 Antibody
Description
Overview of Siglec-6 Antibody
Siglec-6 (Sialic acid-binding immunoglobulin-type lectin 6) is a transmembrane receptor expressed on mast cells and placental trophoblasts. Agonistic antibodies targeting Siglec-6 inhibit MC activation by promoting receptor internalization and downstream inhibitory signaling .
Mechanism of Action
Siglec-6 antibodies exert therapeutic effects through:
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Receptor Internalization: Antibody engagement induces rapid Siglec-6 internalization, reducing surface receptor availability .
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Inhibitory Signaling: Agonistic binding activates intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs), suppressing MC degranulation and cytokine release .
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Epitope-Dependent Activity: Functional outcomes vary based on antibody binding regions (Table 1) .
Table 1: Functional Properties of Siglec-6 Antibodies by Epitope Region
Critical Observations:
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Potency Correlation: Antibodies targeting membrane-proximal regions showed 10-fold higher inhibition (IC₅₀ 0.1 nM) compared to distal binders .
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Species Specificity: Humanized variants maintained cross-reactivity with primate Siglec-6 but not murine homologs .
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Safety Profile: No off-target binding observed in transcriptomic screens of human tissues .
Therapeutic Applications
Siglec-6 antibodies are under investigation for:
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Chronic Urticaria: Suppressed histamine release in ex vivo MC models .
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Asthma: Reduced airway hyperresponsiveness in preclinical murine studies .
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Anaphylaxis: Phase I trials demonstrated dose-dependent inhibition of IgE-mediated reactions .
Comparative Advantages Over Existing Therapies
| Parameter | Siglec-6 Antibody | Omalizumab (Anti-IgE) | Corticosteroids |
|---|---|---|---|
| Target Specificity | High (MC-selective) | Moderate | Low |
| Onset of Action | <1 hour | 2–4 weeks | 6–12 hours |
| Adverse Effects | Minimal | Anaphylaxis risk | Systemic toxicity |
Developmental Status
As of March 2025, one anti-Siglec-6 antibody (designation undisclosed) has entered Phase II trials for chronic spontaneous urticaria, with preliminary data showing:
Product Specs
Constituents: 50% Glycerol, 0.01M Phosphate Buffered Saline (PBS), pH 7.4
Target Background
KEGG: cel:CELE_F28H7.9
UniGene: Cel.26638
Q&A
FAQs for IL-6 Antibody Research
Advanced Research Questions
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How can researchers resolve contradictions in IL-6-dependent autoantibody production data?
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What strategies improve IL-6 antibody engineering for dual specificity (neutralization and detection)?
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Computational design: Use covariation analysis and Rosetta-based stability predictions to engineer single-chain variable fragments (scFvs) with high affinity (e.g., melting temperature improved from 51°C to 82°C) .
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Functional validation: Test neutralizing capacity via STAT3 phosphorylation assays and compare to clinical benchmarks like Siltuximab .
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Data Tables
Table 1: Key IL-6 Antibody Pairs for Assay Development
| Capture Antibody | Detection Antibody | Application | Sensitivity | Source |
|---|---|---|---|---|
| Mouse Anti-Human MAB9540 | Biotinylated MAB2063 | ELISA | <10 pg/mL | |
| IL-6 fusion protein | 21865-1-AP (Rabbit IgG) | WB, IHC, IP | 20 kDa band |
Table 2: Common Pitfalls in IL-6 Antibody Research
Methodological Recommendations
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For mechanistic studies: Combine IL-6 blockade (e.g., HZ-0408b ) with transcriptomic profiling to dissect pro-inflammatory vs. anti-inflammatory roles in arthritis or lupus .
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For reproducibility: Follow standardized characterization protocols (e.g., Nature’s antibody validation guidelines ) to address the “antibody crisis” affecting 50% of commercial reagents .
