High-avidity human serum antibodies recognizing linear epitopes of Borna disease virus proteins.

This study explores the specificity of antibodies that react with Borna disease virus (BDV), focussing particularly on those found in psychiatric patients. The researchers developed a testing method to identify antibodies acting against two main proteins of BDV. They found that the antibodies taken from these patients did indicate an infection with BDV or a similar agent; however, the reasons for the poor development of their affinity remains unclear.

Research Methods and Results

• The researchers created a peptide array-based screening test that was capable of identifying antibodies which combat linear epitopes of the two primary BDV proteins, the nucleoprotein (N) and the phosphoprotein (P).
• Initial tests were carried out using sera from BDV-infected mice and rats, and horses afflicted with Borna disease. These tests found the screening had high specificity and sensitivity. All sera from the infected animals recognized either N, P, or both. On the other hand, sera of non-infected animals showed no reactions on either peptide array.
• Investigation was carried out on several human sera that recognized BDV antigen via indirect immunofluorescence. They found that these contained antibodies that identified various linear epitopes in one or both BDV proteins.
• Notably, antibodies which were purified from human serum by matrix-immobilized peptides showed high-avidity, or high binding strength, to BDV antigens when examined by indirect fluorescent antibody (IFA) and Western blotting methods, which are techniques to detect specific proteins in a sample.

Conclusions

• Results from this research suggest that the antibodies found in psychiatric patients that react with BDV do indicate an active infection with BDV or a similar agent.
• This is significant because previous research has called the diagnostic value of these antibodies into question, suggesting the antibodies might be reacting to antigenically related microorganisms or self-antigens rather than to BDV itself.
• Despite these findings, the researchers were not able to explain why the affinity maturation of these BDV-specific antibodies in humans was poor. Affinity maturation refers to the improvement of antibody binding to its target antigen over time, crucial for an efficient immune response. The researchers indicate that further investigation into this area is necessary.