Therapy-induced antibodies to interferon-alpha 2a recognise its receptor-binding site

Area of Science:

• Immunology
• Virology
• Biochemistry

Background:

• Chronic hepatitis B and C are significant global health concerns.
• Recombinant human interferon-alpha 2 (rIFN-alpha 2) is used in treating these viral infections.
• The development of anti-IFN antibodies can impact treatment efficacy.

Purpose of the Study:

• To investigate the antibody response in patients treated with rIFN-alpha 2.
• To characterize the epitopes recognized by therapy-induced antibodies against rIFN-alpha 2.
• To determine if these antibodies interfere with rIFN-alpha 2 binding to cells.

Main Methods:

• Serum samples from 58 patients with chronic hepatitis B or C, treated with rIFN-alpha 2, were analyzed.
• Competitive radioimmunoassay (RIA) was used with monoclonal antibodies (MoAbs) to map antibody epitopes.
• The effect of patient antibodies on rIFN-alpha 2 binding to human cells was assessed.

Main Results:

• Antibodies to rIFN-alpha 2 were detected in 14 out of 58 patients (12 low-titre, 2 high-titre).
• High-titre antibodies recognized epitopes in the amino-terminal region of rIFN-alpha 2.
• These antibodies specifically targeted the receptor-binding domain (amino acids 30-53) of rIFN-alpha 2.
• Patient-derived anti-IFN antibodies inhibited the binding of rIFN-alpha 2 to human cells.

Conclusions:

• Therapy-induced antibodies in patients with chronic hepatitis B or C target the receptor-binding domain of rIFN-alpha 2.
• These antibodies can neutralize interferon activity by blocking cell binding.
• Understanding these antibody responses is important for optimizing interferon-based therapies.