Yes, nuclear proteins can play a significant role in the pathogenesis of allergic diseases through multiple mechanisms. Here’s a concise overview of their effects:
### **1. As Damage-Associated Molecular Patterns (DAMPs)**
- **Extracellular nuclear proteins (e.g., HMGB1, histones)** released during cell stress or death activate immune responses via **TLRs (e.g., TLR4, TLR9)** and **RAGE**, promoting inflammation in asthma, atopic dermatitis, and allergic rhinitis.
- **Neutrophil extracellular traps (NETs)**, containing DNA and histones, exacerbate allergic inflammation by enhancing Th2 responses.
### **2. Regulation of Th2 Immunity**
- **Transcription factors (STAT6, GATA3, NF-κB)** drive Th2 differentiation and IgE production.
- **Epigenetic modifications** (e.g., histone acetylation/methylation) regulate expression of allergy-related genes (IL-4, IL-5, IL-13).
### **3. Autoallergy & Autoantibodies**
- **Anti-nuclear antibodies (ANAs)** in some chronic urticaria or eczema patients suggest autoimmune involvement.
- **Molecular mimicry** between viral/bacterial nuclear proteins and self-antigens may trigger cross-reactive IgE.
### **4. Therapeutic Implications**
- **HMGB1 inhibitors** (e.g., glycyrrhizin) and **JAK-STAT inhibitors** are being explored for allergic diseases.
- **HDAC inhibitors** modulate allergic inflammation in preclinical models.
### **Conclusion**
Nuclear proteins contribute to allergy pathogenesis via **immune activation, epigenetic regulation, and autoimmunity**, making them potential biomarkers or therapeutic targets. Further clinical studies are needed to validate their roles.
