Individual myasthenia gravis autoantibody clones can efficiently mediate multiple mechanisms of pathology

Pham, Minh C.; Masi, Gianvito; Patzina, Rosa; Obaid, Abeer H.; Oxendine, Seneca R.; Oh, Sangwook; Payne, Aimee S.; Nowak, Richard J.; O’Connor, Kevin C.

doi:10.1007/s00401-023-02603-y

Cited by 10 publications

References 75 publications

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Visualization and characterization of complement activation in acetylcholine receptor antibody seropositive myasthenia gravis

Huang,

Sandholm,

Persson

et al. 2024

Muscle and Nerve

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Introduction/AimsThere are no blood biomarkers to monitor treatment effects in myasthenia gravis (MG) or studies visualizing the acetylcholine receptor (AChR) antibody‐induced membrane attack complex (MAC) at the human muscle membrane. This study aimed to compare levels of complement activation products and native complement components in MG patients and healthy controls (HCs) and to model the AChR antibody‐mediated attacks in human muscle cells.MethodsWe assessed the complement components and activation product levels with enzyme‐linked immunosorbent assay and magnetic bead‐based sandwich assays in plasma and sera of 23 MG patients and matched HCs. Receiver operator characteristic (ROC) curve analysis evaluated the diagnostic accuracy. Complement levels were correlated with the myasthenia gravis composite (MGC) scores. AChR+ MG modeling in human muscle cells used sera from nine MG patients and three HCs.ResultsMG patients had significantly higher plasma levels of C3a (p < .0001), C5 (p = .0003), and soluble C5b‐9 (sC5b‐9; p < .0001) than HCs. The ROC curve analysis showed a clear separation between MG patients and HCs for plasma C3a (AUC = 0.9720; p < .0001) and sC5b‐9 (AUC = 0.8917, p < .0001). MG patients had higher levels of plasma complement Factor I (FI; p = .0002) and lower properdin levels (p < .0001). The MGC had moderate correlations with plasma Factor B (FB), FI, and Factor H. AChR+ MG patient sera triggered the deposition of MAC and reduced AChRs.DiscussionWe suggest validating plasma C3a and sC5b‐9 as blood biomarkers for complement activation in MG. Further, the in vitro study allowed visualization of MAC deposition after applying AChR+ MG sera on human muscle cells.

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