Abstract
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. Activation of the complement pathway in autoimmune diseases can lead to a secondary complement deficiency resulting in reduced complement activity, due to consumption, during episodes of disease activity. It is not clear whether complement activity in MG patients associates with measurements of disease activity or the titer of circulating pathogenic AChR autoantibodies. To explore such associations, as a means to identify a candidate biomarker, we measured complement activity in AChR MG samples (N = 51) using a CH50 hemolysis assay, then tested associations between these values and both clinical status and AChR autoantibody titer. The majority of the study subjects (88.2%) had complement activity within the range defined by healthy controls, while six patients (11.8%) showed reduced activity. No significant association between complement activity and disease status or AChR autoantibody titer was observed.
Highlights
The most common subtype of autoimmune myasthenia gravis (MG) is characterized by pathogenic autoantibodies targeting the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction [1]
The majority of Acetylcholine receptor (AChR) MG samples (88.2%) had complement activity within the range defined by the healthy controls (HC) (Fig 1A)
We first compared the complement activity between immunotherapy naïve and nonimmunotherapy naïve samples and found no significant difference between these two groups (Fig 1B)
Summary
The most common subtype of autoimmune myasthenia gravis (MG) is characterized by pathogenic autoantibodies targeting the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction [1]. These autoantibodies directly contribute to disease pathology primarily, though not exclusively, through activation of complement. The three different complement activation pathways, namely the classical, alternative and lectin pathway, differ in their initial steps, but all converge at the C3 activation step [5]. The classical pathway is activated when C1q binds to antibody– antigen complexes [6], the alternative pathway is the result of spontaneous hydrolysis of C3 which can lead to rapid complement activation on foreign cell surfaces [7] and the lectin
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