EIF2B Antibody

EIF2B Antibody: Definition and Research Applications

EIF2B antibodies are immunoreagents designed to detect specific subunits (α, β, γ, δ, ε) of the EIF2B complex. These antibodies are widely used in:

• Western Blot (WB): Detecting EIF2B subunits (~38–85 kDa depending on the subunit) in lysates from human, mouse, and rat tissues .

• Immunohistochemistry (IHC): Localizing EIF2B expression in paraffin-embedded tissues (e.g., mouse kidney) .

• Immunofluorescence (IF): Visualizing cytoplasmic EIF2B bodies in stress granules or disease models .

• Radioimmunoprecipitation (IP): Identifying autoantibodies against EIF2B in systemic sclerosis (SSc) sera .

Clinical Significance of Anti-EIF2B Antibodies

Anti-EIF2B autoantibodies are detected in ~2.5–7% of systemic sclerosis (SSc) patients and are strongly associated with:

• Interstitial Lung Disease (ILD): 100% of anti-EIF2B-positive SSc patients showed ILD in imaging studies .

• Diffuse Cutaneous SSc (dcSSc): 89% of anti-EIF2B-positive cases presented with dcSSc .

• Cytoplasmic Staining Pattern: Distinct from antinuclear antibodies (ANA), aiding in SSc diagnosis .

Table 2: Clinical Features of Anti-EIF2B-Positive SSc Patients

EIF2B in Neurological and Metabolic Disorders

Mutations in EIF2B1–5 genes cause vanishing white matter disease (VWM), a fatal leukoencephalopathy. Key findings include:

• Pathogenic Mechanisms: VWM mutations destabilize EIF2B decamers, impairing GTP-GDP exchange and triggering maladaptive integrated stress response (ISR) .

• Therapeutic Interventions: Small-molecule EIF2B activators (e.g., ISRIB, 2BAct) restore translation in VWM models by stabilizing EIF2B complexes .

Regulation of EIF2B Activity

EIF2B function is modulated by:

• Phosphorylation: Stress-activated kinases (e.g., PKR, PERK) phosphorylate EIF2α, converting EIF2 into a competitive EIF2B inhibitor .

• Post-Translational Modifications (PTMs): EIF2Bε undergoes phosphorylation (e.g., Ser-544 by GSK3β) and ubiquitination, altering its activity .

Table 3: Key PTMs of EIF2Bε

Research Tools and Future Directions

• Antibody Validation: Commercial EIF2B antibodies are validated for specificity using knockout lysates and immunodepletion assays .

• Emerging Therapies: Preclinical studies highlight EIF2B activators as promising candidates for VWM and ISR-related disorders .