Complement activity in myasthenia gravis is independent of autoantibody titer and disease severity

Acetylcholine receptor (AChR) autoantibodies, found in patients with autoimmune myasthenia gravis (MG), can directly contribute to disease pathology through activation of the classical complement pathway. Accordingly, complement inhibitors are used as a therapeutic strategy, but the response can be heterogeneous even though AChR autoantibodies are present. The mechanisms underlying the variable response are not defined. Yet there is a need for further understanding so that responses can be better predicted. There is a broad spectrum of circulating complement activity levels activity among MG patients. It is not clear whether this activity associates with disease burden or the circulating levels of autoantibodies. We measured complement activity and investigated these associations in MG patients as a means to explore candidate biomarkers. Most study subjects had complement activity within the range defined by healthy controls and no association between this activity and disease burden or AChR autoantibody titer was observed. Assays measuring the complement activating properties of AChR autoantibodies are needed to identifying patients expected to respond to complement inhibitor-based treatments.