Improving sensitivity of autoantibody testing for myasthenia gravis using cell-based assays: an evaluation of strategies that may be used in clinical practice.

INTRODUCTION

Testing for acetylcholine receptor and muscle-specific kinase antibodies (anti-AChR and anti-MuSK) is of central diagnostic importance in myasthenia gravis (MG), yet practical evaluations of strategies to improve sensitivity using cell-based assays (CBAs) are lacking. We evaluated strategies to improve sensitivity of autoantibody testing for MG using CBAs at our center, including repeat fixed CBA at routine 1:10 dilution, send-out live CBA, and fixed CBA at lower 1:5 dilution.

METHODS

Quality improvement/quality assurance (QI/QA) evaluation of all patients at London Health Sciences Centre/St. Joseph's Health Care London (LHSC/SJHC) who underwent anti-AChR/MuSK fixed CBA testing from January 2023-January 2026.

RESULTS

During the 3-year evaluation period, 973 patients underwent anti-AChR/MuSK fixed CBA at routine 1:10 dilution. Of these, 127 (13.1%) exhibited autoantibody positivity, 3 (0.3%) were indeterminable, and 843 (86.6%) were negative. Testing of 78 patients represented repeat testing after initially negative anti-AChR/MuSK fixed CBA, of whom 4 (5%) were positive. Thirteen patients with negative/indeterminable anti-AChR/MuSK fixed CBA underwent send-out live CBA, of whom 4 (31%) were positive. Of all 131 anti-AChR/MuSK-positive patients identified, 123 (94%) had positivity on initial fixed CBA, 4 (3%) on repeat fixed CBA, and 4 (3%) on send-out live CBA. Among 8 samples with negativity by fixed CBA at 1:10 dilution from patients with subsequent autoantibody positivity, 4 (50%) exhibited positivity at 1:5 dilution.

CONCLUSION

Repeat fixed CBA at routine 1:10 dilution, send-out live CBA, and fixed CBA at lower 1:5 dilution are all strategies that may improve sensitivity of autoantibody testing for MG at our center.