Novel autoantibodies against the proteasome subunit PSMA7 in amyotrophic lateral sclerosis

To identify autoantibodies using sera from ALS patients and elucidate their roles in disease pathology.

An immunological screening was performed with a phage expression library SEREX method using sera from 3 ALS patients to identify ALS-related autoantibodies. Levels of antibodies identified by SEREX were measured in 33 ALS patients and 30 normal controls (NCs) by AlphaLISA using recombinant non-full-length proteins. The results were then validated by ELISA using full-length proteins in 71 ALS patients, 30 NCs and 34 disease controls (DCs). The relationship between the titres and clinical profiles of ALS patients were examined.

Four autoantibodies identified by SEREX were proteasome subunit alpha type 7 (PSMA7), vimentin, hydroxymethylbilane synthase and TBC1 domain family member 2 (TBC1D2). AlphaLISA revealed that only the anti-PSMA7 and anti-TBC1D2 levels were significantly different between the ALS and NCs groups. ELISA showed that only the levels of antibody against PSMA7, involved in protein degradation by the ubiquitin-proteasome pathway (UPP), were higher in the ALS group than both the NC (P < .01) and DC (P = .034) groups. Anti-PSMA7 levels tended to be negatively correlated with the logarithm of disease duration (P = .052) and were significantly positively correlated with the logarithm of creatine kinase levels (P = .011). The anti-PSMA7 antibody levels were different between patients with and without dysphagia (P < .01).

Serum anti-PSMA7 antibody might be a disease-promoting factor in early-stage ALS and might be a biomarker of ALS. Anti-PSMA7 autoantibody might contribute to the pathogenesis of ALS, possibly via its role in the UPP.