Autoantibodies to the proteasome in monosymptomatic optic neuritis may predict progression to multiple sclerosis

Abstract

Objective. Proteasome autoantibodies (PAB) have been found in multiple sclerosis (MS) patient sera and cerebrospinal fluid (CSF). Presence of PAB could thus be a possible diagnostic marker for MS. We investigated whether PAB serum status in acute monosymptomatic optic neuritis (ON) and MS differed significantly from that of healthy controls, and whether or not PAB status is predictive of later MS development in patients with ON. Material and methods. Sera from ON patients, MS patients and healthy donors were analysed retrospectively using ELISA. Subsequently, a small group of PAB‐positive samples were subjected to SDS‐PAGE, immunoblotting and 2‐D PAGE. Results. We found that 20 % (6/30) ON patients, 47 % (22/47) MS patients and 9 % (7/81) controls tested PAB positive using ELISA analysis. High PAB levels were found in 2 (4 %) MS patients, 1 (3 %) ON patient and 2 (3 %) controls. PAB positivity in ELISA was confirmed by immunoblotting. Separation of proteasome subunits by 2D PAGE followed by immunoblotting revealed no particular PAB subunit preference. Conclusions. A retrospective search in available patient files revealed that 6 of 6 (100.0 %) PAB‐positive ON patients developed MS over time. Eight of 24 (33 %) PAB‐negative ON patients developed MS over time and 47 % (14/30) of all ON patients developed MS. A series of patient CSF was analysed by ELISA to assess the possible correlation between PAB status of concurrent serum and CSF samples, but no correlation was found. However, the results from the six PAB‐positive ON patients could potentially be of prognostic value.

• Autoantibodies
• multiple sclerosis
• optic neuritis
• proteasome
• specificity
• two‐dimensional gel electrophoresis

Acknowledgements

Thanks to laboratory technicians Brian Hauschildt and Dorthe Tange Olsen at Statens Serum Institut for excellent technical work