Two cases of coexisting neuromyelitis optica spectrum disorder (NMOSD) and myasthenia gravis (MG) suggest a possible etiopathogenetic link between the diseases, reports a study published in Multiple Sclerosis and Related Disorders.

Using next-generation sequencing (NGS), 2 mutant human leukocyte antigen (HLA) alleles were found in common between the 2 patients—HLA-DQA1*05:01:01 and HLA-DPB1*04:02:01.

“To summarize, although the exact pathogenesis, genetic mechanisms, and triggering factors underlying MG and [NMOSD] remain unknown, the coexistence suggests an aetiopathogenetic link between these two diseases,” the study’s authors said.


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Sequencing also revealed 2 HLA alleles commonly associated with MG, HLA-A*01:01:01 and HLA-DRB1*03:01, in the first patient. The second patient was found to have the HLA-C*07:01:01 allele, which has been characterized as a risk factor for MG, as well as HLA-DQB1*05:02:01 which has been previously observed in both MG and NMOSD patients.

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“As immunogenetics is likely to play an important role in the pathogenesis of autoantibody-associated autoimmune neurological diseases, HLA could help identify the possible association between the two diseases leading to a better management of patients, especially those with atypical presentations,” the authors suggested.

Both patients in the study were female and diagnosed with MG after experiencing symptoms including dysarthria and dysphagia and testing positive for acetylcholine receptor (AChR) antibodies. MG symptom resolution was experienced in both patients following thymectomy. Histology revealed no evidence of thymoma in either case.

Patient 1 later experienced cervical pain and weakness that transitioned to hemiplegia after a herpes zoster outbreak. NMOSD was diagnosed following imaging results and a positive antibody test to aquaporin-4 (AQ4). She was treated with 6 courses of plasma exchange and regained the ability to walk. Disease control is being maintained with rituximab.

The second patient experienced blurred vision and retrobulbar pain leading to a diagnosis of optic neuritis. She was also found to be positive for anti-AQ4 and has been treated with azathioprine for disease maintenance. 

Reference

Vakrakou A, Chatzistamatiou T, Koros C, et al. HLA-genotyping by next-generation-sequencing reveals shared and unique HLA alleles in two patients with coexisting neuromyelitis optica spectrum disorder and thymectomized myasthenia gravis: immunological implications for mutual aetiopathogenesis? Mult Scler Relat Disord. 2022;103858. doi:10.1016/j.msard.2022.103858