Subunit specificity of the acetylcholine receptor antibodies in double seropositive myasthenia gravis

Zouvelou, Vasiliki; Michail, Maria; Belimezi, Maria; Zisimopoulou, Paraskevi

doi:10.1002/mus.27177

Cited by 3 publications

(4 citation statements)

References 7 publications

(5 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, there was no difference in the patient's clinical profile when the anti-nAChR autoAbs titer increased, probably due to the presence of only anti-γ autoAbs ( Table 1 ). By these observations, we had previously reported a double positive MG patient (anti-nAChR and anti-MuSK autoAbs positive) who was presented with MuSK phenotype ( 25 ). This patient's clinical manifestation of the disease was not affected by the increase of the anti-nAChR autoAbs titer.…”

Section: Discussionmentioning

confidence: 81%

“…After immunoadsorption, we showed that in all sera from different time points, the patient had relatively small amounts of anti-α1 autoAbs and the vast majority of autoAbs were directed against the β1 and γ subunits. We concluded that the patient did not show any clinical deterioration, because the pathogenic anti-α1 autoAbs were always in low concentration, while the increase of the anti-nAChR autoAbs titer was attributed to the increase of only the less pathogenic anti-β1 and anti-γ autoAbs ( 25 ).…”

Section: Discussionmentioning

confidence: 92%

“…Each subunit consists of a ~210 amino acid extracellular domain (ECD), bearing the epitopes for potential pathogenic autoAbs ( 21 , 22 ). Although the α1 subunit hosts the main immunogenic region, patients with MG also harbor autoAbs against the non-α1 subunit-ECDs ( 22 – 25 ). AutoAbs against the α1 subunit of the nAChR are characterized as more pathogenic than those against the β1 subunit ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Analysis of nAChR Autoantibodies Against Extracellular Epitopes in MG Patients

et al. 2022

Self Cite

View full text Add to dashboard Cite

Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies targeting components of the postsynaptic membrane of the neuromuscular junction (NMJ), leading to neuromuscular transmission deficiency. In the vast majority of patients, these autoantibodies target the nicotinic acetylcholine receptor (nAChR), a heteropentameric ion channel anchored to the postsynaptic membrane of the NMJ. Autoantibodies in patients with MG may target all the subunits of the receptor at both their extracellular and intracellular regions. Here, we combine immunoadsorption with a cell-based assay to examine the specificity of the patients' autoantibodies against the extracellular part of the nAChR. Our results reveal that these autoantibodies can be divided into distinct groups, based on their target, with probably different impacts on disease severity. Although our findings are based on a small sample group of patients, they strongly support that additional analysis of the specificity of the autoantibodies of patients with MG could serve as a valuable tool for the clinicians' decision on the treatment strategy to be followed.

show abstract

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Analysis of nAChR Autoantibodies Against Extracellular Epitopes in MG Patients

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…The mechanisms by which AChR-Ab and MuSK-Ab cause pathologies in DSP-MG have not been deciphered. Analysis of subunit specificity of AChR-Ab in a DSP-MG patient revealed the presence of autoantibodies against β1 and γ subunits rather than the dominant α1 subunit, potentially explaining the resemblance between MuSK-MG and DSP-MG. 47 There lies as well the possibility that the pathological effects of MuSK-Ab could interfere with those of AChR-Ab or vice versa to some extent, and thus the phenotype of DSP-MG may still vary among patients.…”

Section: Discussionmentioning

confidence: 99%

Clinical Features and Prognostic Analysis of MuSK-Antibody-Positive Myasthenia Gravis versus Double-Seropositive Myasthenia Gravis: A Single-Center Study from Central South China

He,

Chen,

et al. 2024

NDT

View full text Add to dashboard Cite

Purpose To decipher the discrepancies between muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) and double-seropositive myasthenia gravis (DSP-MG), and to determine prognostic factors for minimal manifestation status (MMS) achievement in MG patients with MuSK autoantibodies (MuSK-Ab). Patients and Methods A total of 34 MG patients seropositive for MuSK-Ab were enrolled in this study. The demographic and clinical features were compared between MuSK-MG (n = 28) and DSP-MG (n = 6) patients, and factors affecting MMS induction in all patients with MuSK-Ab were identified using Cox regression analysis. Results Compared to MuSK-MG patients, those with DSP-MG had similar clinical characteristics, except that they had a lower frequency of bulbar muscle involvement at nadir (50% vs 92.9%; P = 0.029) and higher proportions of comorbidities with diabetes mellitus (33.3% vs 0%; P = 0.027) and thymic abnormalities (33.3% vs 0%; P = 0.027). Higher MG Activities of Daily Living (MG-ADL) scores (HR = 0.16, 95% CI: 0.037–0.7, P = 0.015) and axial muscle involvement at nadir (HR = 0.39, 95% CI: 0.16–0.94, P = 0.035) were negative prognostic factors for MMS achievement in patients with MuSK-Ab regardless of acetylcholine receptor antibody (AChR-Ab) positivity. Multivariable Cox regression analysis further established higher MG-ADL scores at the nadir (HR = 0.19, 95% CI: 0.04–0.94; P = 0.042) as an independent risk factor for MMS achievement. Conclusion DSP-MG was comparable to MuSK-MG and could be considered a single entity in our cohort. In all MG patients with MuSK-Ab, a higher MG-ADL score at nadir may herald a lower chance of MMS achievement, with no observed potential effect of AChR-Ab presence.

show abstract