Paraneoplastic myasthenia gravis: Detection of anti-MGT30 (titin) antibodies predicts thymic epithelial tumor

Abstract

It has been suggested that antibodies against non-acetylcholine receptor proteins of striated muscle are markers of the presence of a thymic epithelial tumor in patients with myasthenia gravis (MG). These antibodies may be measured using an immunofluorescence assay against striated muscle (anti-STR) or an ELISA with a recombinant 30-kd titin fragment (anti-MGT30). To directly compare anti-STR with anti-MGT30, we examined the sera of 276 consecutive patients with known or suspected MG. Definite diagnoses and thymic histology, if available, were correlated with the antibody assays. Of the 276 patients, 164 had MG. Thymic histology was obtained in 44 patients: 18 had lymphofollicular hyperplasia, 13 thymic epithelial tumors, 8 atrophy, and 5 were normal. When compared with anti-STR, anti-MGT30 showed a sensitivity of 69% (STR 77%), specificity of 100% (STR 56%, p = 0.026), negative predictive value of 82% (STR 77%), and positive predictive value of 100% (STR 56%, p = 0.003) for the identification of a thymic epithelial tumor versus thymic hyperplasia. We conclude that the anti-MGT30 ELISA is better than the anti-STR immunofluorescence assay for the diagnosis of paraneoplastic MG.

Skeletal muscle titin: physiology and pathophysiology

“…The titin antibody assay is clinically useful, since 95% of thymoma MG patients have antibodies reacting with the titin MIR epitope. When combining the titin antibody assay with CT scanning of the thymus, the titin antibodies have a near 100% specificity of detecting a thymoma [52]. The presence of titin antibodies also shows some correlation with MG severity [53], and titin antibody-positive MG patients benefit less from thymectomy than MG patients without titin antibodies.…”

Anti-titin antibodies are not associated with a specific thymoma histology

“…Furthermore, in a series of 276 patients, we could confirm the clinical usefulness of measuring anti-titin antibodies for predicting the presence of a thymic epithelial tumour in patients with myasthenia gravis that was significantly better than the conventional antistriational antibody test. 2 This has been confirmed independently, at least for patients under the age of 60.…”

“…A total of 28 myasthenia gravis patients with pairs of thymoma histology and serum were analysed, 13 from the 1997 study, 2 an additional nine from the University of Barcelona (II), five from the Case Western University Cleveland (HK), and one additional patient from the University of Tübingen (NS). No thymoma patients without myasthenia gravis were analysed.…”

“…[1][2][3] If consistent with radiology, thymectomy is performed also to exclude the presence of an infiltrating thymic carcinoma. As our data now show, titin antibodies are not correlated with thymoma histology and therefore do not add to the presurgical information on the tumour.…”

Thymectomy in Nonthymoma Early-Onset Myasthenia gravis in Correlation with Disease Severity and Muscle Autoantibodies

“…While the concentration of AChR antibodies is highest in early-onset MG [7], the occurrence of titin and RyR antibodies is highest in late-onset MG [23, 33, 34]and is accompanied by a more severe disease in late-onset MG [22, 23, 35, 36]. Histologically, thymic hyperplasia is seen in thymuses from early-onset MG patients, while thymuses from late-onset MG patients are atrophic [28, 37, 38, 39].…”