Development of differential diagnostic marker using peptide microarray in central nervous system demyelinating disease in Korea: pilot study

Abstract

Background: Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are representative diseases of central nervous system (CNS) demyelinating disorders. The detection of aquaporin 4 antibody (AQP4 Ab) has made it easier to differentiate from MS, however it still remains difficult to differentiate with seronegative NMOSD, which accounts for about 20 %.

Objective: We aimed to distinguish AQP Ab-positive and -negative NMOSD, and MS by peptide antibody reactivity of sera.

Methods: We set up customized microarray with 5,126 peptides that included human and viral antigens. We tested sera from 7 patients with seropositive NMOSD (n=2), seronegative NMOSD (n=1), MS (n=2), and healthy control group (n=2).

Results: We observed predominantly strong antibody responses with high signal to noise ratios; some common responses were found for adjacent peptides in cytomegalovirus (CMV) envelope glycoprotein B and Epstein-Barr virus nuclear antigen 1 (EBV -EBNA1) in all screened groups. Several sequences of EBV-EBNA1 showed highly reactivation in seropositive NMOSD, however, it was not observed in MS nor seronegative NMOSD. In NMOSD group, GFAP reactivation was observed. Additionally, other viral antigens including herpes simplex virus, varicella zoster virus were not distinguishable strong responses in screened patients.

Conclusion: We performed pilot study to distinguish the NMOSD and MS using peptide microarray. Several peptide antibody reactivations such as EBV-EBNA1, GFAP seem to be promising as differential diagnostic markers in CNS demyelinating diseases. We need to further evaluation to confirm these findings in larger study.