Thymomas express epitopes shared by the ryanodine receptor

doi:10.1016/0165-5728(95)00106-C

Journal of Neuroimmunology

Volume 62, Issue 1, October 1995, Pages 79-83

https://doi.org/10.1016/0165-5728(95)00106-C Get rights and content

Abstract

Myasthenia gravis (MG) patients with thymoma have antibodies against ryanodine receptor (RyR) of skeletal and heart muscle. In this study, thymomas were examined for reactivity with a panel of polyclonal rabbit antibodies against various short peptides of RyR. An antibody against peptide C2 in the transmembrane region of RyR stained thymoma epithelial cells in crγδsections of 17/23 thymomas, and detected a 40-kDa peptide in Western blotting of a thymoma membrane fraction. The other RyR antibodies did not react with thymoma tissue. The anti-C2 RyR antibody did not react with normal thymus, tonsil or carcinoma of colon. The results strongly indicate that epithelial thymoma cells express an epitope shared by the transmembrane region of skeletal and cardiac muscle RyR.

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In non-thymic cancers, paraneoplastic autoimmune diseases typically emerge from immune processes directed to autoantigens that are common to the cancer and the target organ (Dalmau et al., 1992). By contrast, thymomas do not express bona fide complete AChR, titin, and RYR proteins (Marx et al., 1992; Mygland et al., 1995; Siara et al., 1991) but rather proteins with cross-reacting AChR, titin, and RYR epitopes (Marx et al., 1996; Mygland et al., 1995; Romi et al., 2002; Schultz et al., 1999). In this study, we confirm the TAMG-associated overexpression of the mid-size neurofilament gene, NEF, which harbors sequences coding for AChR and titin epitopes (Marx et al., 1996; Schultz et al., 1999).
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Thymoma MG accounts for around 10–15% of all MG cases [6,7]. The immune response against an epitope expressed on thymoma cells spills over to neuromuscular junction components sharing the same epitope [8••,15]. In thymoma MG, epitopes are shared between the thymoma and muscle proteins.
Myasthenia gravis (MG) is an autoimmune antibody-mediated disease characterized by muscle weakness and fatigability. It is believed that the initial steps triggering humoral immunity in MG take place inside thymic tissue and thymoma. The immune response against one or several epitopes expressed on thymic tissue cells spills over to neuromuscular junction components sharing the same epitope causing humoral autoimmunity and antibody production. The main cause of MG is acetylcholine receptor antibodies. However, many other neuromuscular junction membrane protein targets, intracellular and extracellular proteins are suggested to participate in MG pathophysiology. MG should be divided into subgroups based on clinical presentation and immunology. This includes onset age, clinical characteristics, thymic pathology and antibody profile. The immunological profile of these subgroups is determined by the antibodies present.
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Research paperThymomas express epitopes shared by the ryanodine receptor

Abstract

J. Neuroimmunol.

J. Neuroimmunol.

J. Biol. Chem.

Neuron

J. Biol. Chem.

J. Neuroimmunol.

Clin. Chim. Acta

J. Biol. Chem.

Curr. Opin. Immunol.

Patients with myasthenia gravis and thymoma have in their sera IgG autoantibodies against titin

Clin. Exp. Immunol.

The pathology of the thymus gland in myasthenia gravis

Ann. N.Y. Acad. Sci.

Thymomatous epithelial cells and skeletal muscle share a common epitope defined by a monoclonal antibody

Am. J. Pathol.

Research paper
Thymomas express epitopes shared by the ryanodine receptor