TNFRSF1A Antibody
Description
Definition and Structure
TNFRSF1A Antibody specifically targets the TNFRSF1A receptor (also known as TNFR1 or CD120a), a transmembrane protein that binds TNF-α. Structurally, these antibodies are designed to recognize extracellular or intracellular domains of TNFRSF1A, facilitating:
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Detection: Flow cytometry, Western blot, and immunohistochemistry .
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Neutralization: Blocking TNF-α-induced cytotoxicity by competing for receptor binding .
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Functional studies: Investigating signaling pathways like NF-κB activation or apoptosis .
Mechanisms of Action
TNFRSF1A antibodies exhibit dose-dependent inhibitory effects on TNF-α activity:
Table 1: Neutralization Efficacy of TNFRSF1A Antibodies
Key Findings:
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Clone MAB225 demonstrates high potency, neutralizing TNF-α at nanogram-level concentrations .
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Antibodies like MAB625 require higher doses but effectively suppress TNF-α-mediated inflammation in macrophage studies .
Cancer Biology
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Renal Cell Carcinoma (RCC): TNFRSF1A knockdown via siRNA reduces proliferation (by 40–60%), migration, and invasion in 786-O cells, validating its pro-tumor role .
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Glioma: High TNFRSF1A expression correlates with poor prognosis. Silencing inhibits U251/U87 cell proliferation and migration by 50–70% .
Immune Dysregulation
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TRAPS (TNF Receptor-Associated Periodic Syndrome): Mutations like p.C125Y impair receptor shedding, leading to unregulated inflammation. Antibodies help quantify surface TNFRSF1A levels in CD14+ monocytes .
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Neuropsychiatric Disorders: Elevated serum TNFRSF1A levels are linked to schizophrenia and bipolar disorder, with antibodies used to measure biomarker concentrations .
Table 2: Clinical Correlations of TNFRSF1A Dysregulation
Therapeutic Potential:
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Neutralizing antibodies (e.g., MAB225) are being explored to disrupt TNF-α signaling in cancers and autoimmune diseases .
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In TRAPS, antibody-based assays aid in identifying defective receptor trafficking .
Technical Considerations
Product Specs
Target Background
TNFRSF1A (Tumor Necrosis Factor Receptor Superfamily, Member 1A) is a receptor for TNFSF2 (TNF-α) and homotrimeric TNFSF1 (lymphotoxin-α). Upon activation, the adapter molecule FADD recruits caspase-8, forming a death-inducing signaling complex (DISC). This complex activates caspase-8, initiating a caspase cascade that mediates apoptosis. TNFRSF1A also contributes to non-cytocidal TNF effects, including the induction of an antiviral state and activation of acid sphingomyelinase.
Numerous studies have investigated the association between TNFRSF1A polymorphisms and various diseases. Key findings include:
- Cardiovascular and All-Cause Mortality: Elevated TNFRSF1A levels are linked to increased risk of cardiovascular and all-cause mortality in hemodialysis patients (PMID: 28256549).
- Essential Hypertension: The +36G TNFR1 genetic marker is implicated in the development of essential hypertension in individuals with metabolic syndrome (PMID: 30289218).
- TRAPS (Tumor Necrosis Factor Receptor-Associated Periodic Syndrome): De novo mutations in TNFRSF1A can trigger TRAPS or TRAPS-like symptoms (PMID: 27793577).
- Rheumatoid Arthritis (RA): Studies have yielded conflicting results regarding the association of TNFR1 -609G/T polymorphisms with RA susceptibility (PMID: 29404828).
- Schizophrenia: Specific TNFRSF1A polymorphisms may influence the severity of schizophrenia symptoms in men, potentially contributing to the risk of violent behavior (PMID: 29317797).
- Radiotherapy-Induced Oral Mucositis: Polymorphisms in the TNFRSF1A promoter region are associated with radiotherapy-induced oral mucositis in head and neck cancer patients (PMID: 28401452).
- Autoimmune Thyroid Diseases: While most TNFRSF1A SNPs showed no association with autoimmune thyroid diseases in a Chinese Han population, rs4149570 demonstrated a weak association with Hashimoto's thyroiditis (PMID: 29401539).
- Ankylosing Spondylitis (AS): TNFRSF1A polymorphisms are associated with AS susceptibility, severity, and response to etanercept treatment (PMID: 30075559).
- MOAP-1 Regulation: RACK1 interacts with MOAP-1, influencing its function and highlighting the complexity of MOAP-1 regulation (PMID: 29470995).
- IgA Nephropathy: Serum TNFR1 levels did not significantly decrease after tonsillectomy with steroid pulse therapy in patients with IgA nephropathy (PMID: 28389814).
- Response to Anti-TNFα Therapy: The TNFRSF1A c.625+10 G allele was associated with a delayed response to anti-TNFα therapy (PMID: 29579081).
- Kidney Function: TNFR1 is longitudinally associated with kidney function decline (PMID: 28601698).
- Multiple Sclerosis (MS): Heterozygous mutations in TNFRSF1A were found in a significant proportion of childhood MS patients (PMID: 28927886).
- Additional Studies: Numerous other studies explore the role of TNFRSF1A in diverse conditions including various cancers, inflammatory diseases, and responses to different therapies (See PMIDs: 28116820, 28096440, 27990755, 28667032, 28384542, 28199753, 28115640, 28503569, 27068267, 29148404, 28134085, 28765050, 27791020, 28126963, 28427379, 29212072, 28238825, 27003829, 28830973, 27362805, 28159803, 26598380, 28688764, 27684048, 27332769, 27528091, 28489742, 27062399, 26993379, 28363009, 28367848, 27834853, 26854079, 28150360, 28222663, 27040725, 26289850).
Q&A
How to select and validate TNFRSF1A antibodies for receptor localization studies in mutation models?
Validate antibodies using orthogonal methods:
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Epitope specificity: Use transfected cells expressing wild-type vs. mutant TNFRSF1A (e.g., T79M, G87V) to confirm antibody recognition of conformational epitopes. Flow cytometry with antibodies targeting extracellular domains (e.g., BioLegend 113005) reveals reduced surface expression in TRAPS mutants despite preserved intracellular levels .
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Cross-validation: Pair immunoblotting (Cell Signaling 13377 for intracellular domains) with ELISA for soluble TNFR1 to distinguish membrane-bound vs. shed receptors .
What experimental controls resolve discrepancies in TNFR1 molecular weight across studies?
Unexpected bands (e.g., ~90-100 kDa vs. predicted 55 kDa) arise from:
How to design CRISPR-edited models for studying TNFRSF1A antibody specificity?
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Introduce TNFRSF1A knockout in HEK293 or primary macrophages via dual sgRNA targeting exons 2-3.
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Validate using:
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For mutation studies (e.g., TRAPS variants), use homology-directed repair with ssODN templates to model heterozygous states .
Why do some TNFRSF1A antibodies fail to detect receptors in TRAPS mutants despite normal mRNA levels?
TRAPS mutations (e.g., T79M, G87V) cause:
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Intracellular retention: 62% reduction in surface TNFR1 by flow cytometry vs. 140% increase in whole-cell lysates
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Epitope masking: Conformational changes in extracellular domains reduce antibody binding (test with multiple clones: R&D AF-425-PB vs. BioLegend 113005)
How to integrate TNFRSF1A antibody data with multi-omics datasets?
What methodologies resolve conflicting reports on TNFR1 pro-inflammatory vs. anti-inflammatory roles?
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Conditional knockout models: Myeloid-specific Tnfrsf1a deletion reduces LPS-induced IL-6 by 74% (p=0.003) vs. endothelial deletion showing no effect
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Ligand bias analysis: Compare TNFα vs. lymphotoxin-α signaling using phospho-antibody panels (IkBα S32, JNK T183/Y185)
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Structural modeling: Molecular dynamics simulations predict T79M mutation increases receptor rigidity (ΔRMSF = 1.8Å)
How to optimize TNFRSF1A antibody-based assays for rare mutation detection?
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Digital droplet PCR: Detect mutant allele frequencies <0.1% in PBMCs using probes for T79M (FAM) vs. wild-type (HEX)
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Single-cell cytometry: Combine surface staining (PE-TNFR1) with intracellular SNV detection (PrimeFlow RNA)
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Microfluidic western blotting: Resolve mutant vs. wild-type receptors by charge shift (ΔpI = 0.03 for T90I)
What emerging techniques address TNFRSF1A antibody limitations in autoimmune research?
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Nanobody-based biosensors: Real-time TNFR1 clustering monitored by TIRF microscopy (t1/2 = 4.7 ± 0.3 min)
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Proximity labeling: TurboID-fused antibodies map receptor interactomes (126 novel partners identified)
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Cryo-EM with Fab fragments: 3.8Å structure reveals mutation-induced conformational changes in the CRD2 domain
