Case reportDouble-seropositive myasthenia gravis with acetylcholine receptor and low-density lipoprotein receptor-related protein 4 antibodies associated with invasive thymoma

•We report two patients with AChR/LRP4-MG with invasive thymoma.•LRP4 antibodies can be detected in patients with thymoma-associated MG.•LRP4 antibodies may have a role as an exacerbating factor in double-seropositive MG.•Coexistence of LRP4 antibodies may be associated with predominant bulbar symptoms.

We describe two cases of myasthenia gravis (MG) with double seropositivity for acetylcholine receptor (AChR) and low-density lipoprotein receptor-related protein 4 (LRP4) antibodies (AChR/LRP4-MG) with invasive thymoma. Both cases showed myasthenic weakness, which was restricted to the ocular muscles for >5 months from onset, and then unprovoked severe clinical deterioration supervened with predominant bulbar symptoms. The patients responded adequately to therapeutic intervention. Serum AChR antibody levels at post-intervention were markedly decreased, whereas LRP4 antibodies were almost unchanged in case 1 and slightly decreased in case 2. Although our results suggest that patients with AChR/LRP4-MG are likely to present with more severe symptoms than those with LRP4-MG, none of the previously reported cases had thymomas. Coexistence of autoantibodies may reflect breakdown of self-tolerance caused by invasive thymomas. The main cause affecting symptoms of MG in our cases was probably AChR antibodies, and anti-LRP4 antibodies might have been an exacerbating factor.