Autoantibodies Against Unmodified and Citrullinated Human Endogenous Retrovirus K Envelope Protein in Patients With...

Area of Science:

• Immunology
• Retroviruses
• Rheumatic Diseases

Background:

• Autoantibodies against human endogenous retrovirus K (HERV-K) have been observed in rheumatoid arthritis (RA).
• The specific relevance and targets of these autoantibodies, particularly citrullinated epitopes, remain unclear.
• HERV-K proteins are potential targets in autoimmune responses.

Purpose of the Study:

• To investigate the reactivity of autoantibodies against HERV-K envelope (Env) protein, specifically citrullinated forms.
• To determine the association of anti-HERV-K autoantibodies with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA).
• To explore the correlation of these autoantibodies with clinical and laboratory markers of disease activity and pathogenesis.

Main Methods:

• Immunoblotting and ELISA assays were used to detect antibody reactivity.
• HERV-K Env protein was tested in both unmodified and citrullinated forms (using PAD4).
• Sera/plasma from RA patients, JIA patients, and healthy controls were analyzed.

Main Results:

• Patients with RA and JIA showed elevated autoantibodies against HERV-K Env.
• Anti-HERV-K antibody levels correlated with smoking and myeloperoxidase-DNA complexes.
• A subset of RA patients displayed autoantibodies reactive to citrullinated HERV-K Env, correlating with seropositivity and erosive disease.

Conclusions:

• Immunity against HERV-K is increased in RA and JIA.
• Pathogenic protein citrullination in RA may be linked to anti-HERV-K immune responses.
• HERV-K Env citrullination represents a potential autoantigen in RA pathogenesis.