Multiple antibody detection in ‘seronegative’ myasthenia gravis patients

Hong, Yu; Zisimopoulou, Paraskevi; Τράκας, Νικόλαος; Karagiorgou, Katerina; Stergiou, Christos; Skeie, Geir; Hao, Hongjun; Gao, Xiang; Owe, Jone Furulund; Zhang, X.; Yue, Yao-Xian; Romi, Fredrik; Wang, Q.; Li, H.-F.; Gilhus, Nils Erik; Tzartos, Socrates J.

doi:10.1111/ene.13300

Cited by 63 publications

(61 citation statements)

References 20 publications

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“…Their autoantibodies were simply not detectable by the commercially available and commonly used radioimmunoassay . Accordingly, it is anticipated that seronegative MG will continue to yield to the influence of higher sensitivity assays and to the discovery of new autoantigen targets …”

Section: B‐cell Products: Immunoglobulins That Drive Mg Pathologymentioning

confidence: 99%

B cells in the pathophysiology of myasthenia gravis

et al. 2017

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Myasthenia gravis (MG) is an archetypal autoimmune disease. The pathology is characterized by autoantibodies to the acetylcholine receptor (AChR) in most patients or to muscle-specific tyrosine kinase (MuSK) in others and to a growing number of other postsynaptic proteins in smaller subsets. A decrease in the number of functional AChRs or functional interruption of the AChR within the muscle end plate of the neuromuscular junction is caused by pathogenic autoantibodies. Although the molecular immunology underpinning the pathology is well understood, much remains to be learned about the cellular immunology contributing to the production of autoantibodies. This Review documents research concerning the immunopathology of MG, bringing together evidence principally from human studies with an emphasis on the role of adaptive immunity and B cells in particular. Proposed mechanisms for autoimmunity, which take into account that different types of MG may incorporate divergent immunopathology, are offered. Muscle Nerve 57: 172-184, 2018.

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Section: B‐cell Products: Immunoglobulins That Drive Mg Pathologymentioning

confidence: 99%

B cells in the pathophysiology of myasthenia gravis

et al. 2017

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“…In 20% of the cases it is seronegative, characterized by the negativity of the anti-RACH and anti-MUSK Ac of the techniques of routine detection [5]. We did not find any association with seronegative myasthenia and Biermer's disease in the literature.…”

Section: Discussionmentioning

confidence: 55%

“…This negativity would be due to an imperfect sensitivity of the usual techniques of antibodies against-AChR and MuSK tests and/or the controlled presence of antibodies aimed at unidentified antigenic targets [5].…”

Section: Discussionmentioning

confidence: 99%

Seronegative Myasthenia Gravis and a Biermer’s Anemia: A Rare Association

Djiba¹,

Kane²,

Ndao³

et al. 2017

OJIM

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We report a rare association of seronegative myasthenia gravis and a Biermer's anemia (or pernicious anemia). A Senegalese patient of 31 years has been followed for a vitamin B12 deficiency anemia, 12 months before his hospitalization in our department. She has been admitted for an intense and invalidating fatigability in spite of the correction of anemia, associated to a right ptosis. This clinical picture has electively been improved to the prostigmine test. The electromyography had revealed a compatible decrement with a diagnosis of myasthenia. The positivity of the antibodies anti gastric parietal cells and the twice negativity of the antibody against acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) had permitted to deduct a diagnosis of seronegative myasthenia and Biermer's anemia. The evolution was favorable under substitutive B12 vitamin therapy associated to corticotherapy and azathioprine. We insist on the research and the early treatment of a myasthenia, in a context of Biermer's anemia, before suggestive clinical signs in spite of the negativity of the anti-Rach antibodies and anti-Musk.

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“…6,48,49 Autoantibodies are directed against mostly the muscle type of the acetylcholine receptor, and those against MUSK bind often to conformational epitopes of the protein. Their clinical course and outcome were not different from those with antibodies, though statistical tests of significance were not applied due to the small number.…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies in acquired myasthenia gravis: Clinical phenotype and immunological correlation

et al. 2019

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Background: Data on antibody profile in myasthenia gravis (MG) from India are limited. Objectives: To investigate antibody profile in patients with MG and their clinical correlates. Patients and Methods: Patients of MG (n = 85, M:F::1.1:1, mean age: 39.29 ± 17.3 years, mean symptom duration: 72.94 ± 91.8 months) were evaluated for clinical features, MG foundation of America (MGFA) score, response to treatment, and outcome at last follow-up. Antibodies to acetylcholine receptor (AChR), muscle-specific kinase (MUSK), titin and ryanodine receptor (RYR) were analysed using ELISA.Results: Based on the regional distribution of weakness, the cohort could be categorized as: generalized: 60, ocular: 16 and oculo-bulbar: 9. Sixty patients were followed up for a mean duration of 26.74 ± 13.8 months. Outcome at last follow-up was as follows: remission-22, no remission-33 and dead-5. AChR and MUSK antibodies were detected in 58 and 8 patients, respectively. Frequency of generalized MG, worse MGFA score during the disease course and thymomatous histology significantly correlated with presence of AChR-antibodies, though outcome at last followup was comparable between AChR-antibody positive and negative groups. Patients with MUSK antibodies had oculo-bulbar or generalized MG and frequent respiratory crisis, but majority improved or remitted with treatment. Titin antibodies were detected in 31.8% and RYR antibodies in 32.9%. Their presence did not correlate with age at onset of MG, severity or presence of thymoma. Conclusion: This report highlights the spectrum of antibodies in MG in an Indian cohort. AChR-antibody positivity correlated with clinical severity. Outcome was good in majority of MUSK antibody-positive MG. The role of other antibodies, complementary vs epiphenomenon, remains open. K E Y W O R D S acetylcholine receptor, muscle-specific kinase, myasthenia gravis, ryanodine receptor, titin | 429 NAGAPPA et Al.

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Multiple antibody detection in ‘seronegative’ myasthenia gravis patients

Abstract: Detection of multiple muscle antibodies by more sensitive assays provides additional information in diagnosing and subgrouping of MG and may guide MG treatment.

Cited by 63 publications

References 20 publications

B cells in the pathophysiology of myasthenia gravis

B cells in the pathophysiology of myasthenia gravis

Seronegative Myasthenia Gravis and a Biermer’s Anemia: A Rare Association

Autoantibodies in acquired myasthenia gravis: Clinical phenotype and immunological correlation

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