Expression of Envelope Protein Encoded by Endogenous Retrovirus K102 in Rheumatoid Arthritis Neutrophils

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Autoimmune diseases often involve autoantibodies against proteins from genomic retroelements.
• Epigenetic silencing may be insufficient to prevent immune tolerance breakdown for these proteins.
• Human endogenous retrovirus K (HERV-K) envelope (Env) protein is one such target.

Purpose of the Study:

• To investigate HERV-K expression in rheumatoid arthritis (RA) neutrophils.
• To identify which HERV-K loci produce Env recognized by patient autoantibodies.
• To determine if Env is present on the surface of RA neutrophils.

Main Methods:

• RNA sequencing of RA neutrophils to analyze HERV-K expression.
• Analysis of patient autoantibody recognition of endogenously expressed Env.
• Immunodetection of Env on the surface of immune cells using a monoclonal antibody.

Main Results:

• Only HERV-K102 and HERV-K108 loci showed intact open-reading frames for Env expression.
• HERV-K102 expression was specifically increased in RA neutrophils compared to controls.
• Patient autoantibodies and a monoclonal anti-Env antibody detected Env on RA neutrophils.

Conclusions:

• HERV-K102 is the primary locus responsible for producing Env detectable on RA neutrophil surfaces.
• Increased HERV-K102 expression in RA neutrophils contributes to autoantibody recognition.
• HERV-K108 expression may play a minor role in cell surface Env on neutrophils.