Serological and experimental studies in different forms of myasthenia gravis

• Published in: Annals of the New York Academy of Sciences 2018-02, Vol.1413 (1), p.143-153
• Main Authors: Vincent, Angela, Huda, Saif, Cao, Michelangelo, Cetin, Hakan, Koneczny, Inga, Rodriguez‐Cruz, Pedro, Jacobson, Leslie, Viegas, Stuart, Jacob, Saiju, Woodhall, Mark, Nagaishi, Akiko, Maniaol, Angelina, Damato, Valentina, Leite, M. Isabel, Cossins, Judith, Webster, Richard, Palace, Jacqueline, Beeson, David
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors; active and passive immunization; Agrin; Agrin - immunology; Antibodies; Autoantibodies; Autoantibodies - immunology; Biomarkers; clustered acetylcholine receptor; Connectin; Historical account; Humans; Immunoglobulin G; Immunoglobulin G - immunology; Immunoglobulins; In vivo methods and tests; Kv1.4 Potassium Channel - immunology; LDL-Receptor Related Proteins - immunology; low‐density lipoprotein receptor–related protein 4; Muscles; muscle‐specific kinase; MUSK protein; Myasthenia; Myasthenia gravis; Myasthenia Gravis - classification; Myasthenia Gravis - immunology; Neuromuscular junctions; Patients; Receptor density; Receptor Protein-Tyrosine Kinases - immunology; Receptors, Cholinergic - immunology; Subgroups; Thymoma; Thymus
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/nyas.13592

Antibodies to the acetylcholine receptor (AChR) have been recognized for over 40 years and have been important in the diagnosis of myasthenia gravis (MG), and its recognition in patients of different ages and thymic pathologies. The 10–20% of patients who do not have AChR antibodies are now known to comprise different subgroups, the most commonly reported of which is patients with antibodies to muscle‐specific kinase (MuSK). The use of cell‐based assays has extended the repertoire of antibody tests to clustered AChRs, low‐density lipoprotein receptor–related protein 4, and agrin. Autoantibodies against intracellular targets, namely cortactin, titin, and ryanodine receptor (the latter two being associated with the presence of thymoma), may also be helpful as biomarkers in some patients. IgG4 MuSK antibodies are clearly pathogenic, but the coexisting IgG1, IgG2, and IgG3 antibodies, collectively, have effects that question the dominance of IgG4 as the sole pathologic factor in MuSK MG. After a brief historical review, we define the different subgroups and summarize the antibody characteristics. Experiments to demonstrate the in vitro and in vivo pathogenic roles of MuSK antibodies are discussed.