Antibodies against the main immunogenic region of the acetylcholine receptor correlate with disease severity in myasthenia gravis
- Tomoko Masuda1,
- Masakatsu Motomura1,
- Kimiaki Utsugisawa2,
- Yuriko Nagane2,
- Ruka Nakata1,
- Masahiro Tokuda1,
- Taku Fukuda1,
- Toshiro Yoshimura3,
- Mitsuhiro Tsujihata4,
- Atsushi Kawakami1
- 1Department of Clinical Neuroscience and Neurology, Graduate School of Biomedical Sciences, Nagasaki University, Japan
- 2Department of Neurology, Hanamaki General Hospital, Japan
- 3Nagasaki University School of Health Science, Japan
- 4Department of Neurology, Nagasaki Kita Hospital, Japan
- Correspondence to Dr M Motomura, Department of Clinical Neuroscience and Neurology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan;
Contributors TM designed and conducted the antibody experiments, and wrote the paper. KU and YN diagnosed the patients, conducted the statistical processing and wrote the paper. RN, MT, TF and TY diagnosed the patients and conducted the antibody experiments. MT and AK conceived the study and designed the experiments. MM conceived the study, designed the experiments and wrote the paper.
- Received 22 March 2012
- Revised 1 June 2012
- Accepted 2 June 2012
- Published Online First 4 July 2012
Objective We developed an assay that detects autoantibodies against the main immunogenic region (MIR) located at the extracellular end of the nicotinic acetylcholine receptor (AChR) α subunit, and investigated its clinical relevance in myasthenia gravis (MG).
Methods In this retrospective cohort study, we measured MIR antibody (Ab) titres in sera obtained before treatment and analysed their associations with clinical parameters in 102 MG patients from two neurological centres. MIR Ab titres were determined using a modified competition immunoprecipitation assay in the presence or absence of monoclonal antibody 35.
Results 11 of 23 (47.8%) ocular type and 66 of 72 (91.7%) generalised type MG patients were positive for the presence of MIR Abs, defined as a titre >16.8% (3 SDs above the mean for 70 healthy controls). A significantly higher MIR Ab titre (p<0.001) was shown in generalised type (47.9±19.2%) rather than in ocular type MG patients (16.4±8.4%). Bivariate regression analysis using both titre levels of MIR Ab and routine AChR binding Ab as variables revealed MIR Abs to be an exclusive indicator positively associated with disease severity (Myasthenia Gravis Foundation of America classification, p<0.0001; Quantitative MG score, p=0.008), the presence of bulbar symptoms (p<0.0001) and thymoma (p=0.016), and negatively associated with ocular MG (p<0.0001).
Conclusions MIR Ab titre levels show much better correlations with factors related to disease severity compared with AChR binding Ab titres. The MIR Ab assay may be useful for predicting MG symptom severity, especially for discriminating between ocular and generalised types of MG.
TM and MM contributed equally to this work.
Funding This work was supported in part by the Health and Labour Sciences Research Grant on Intractable Diseases (Neuroimmunological Diseases) from the Ministry of Health, Labour and Welfare, Japan.
Competing interests None.
Ethics approval The ethics committees from Nagasaki University and Hanamaki General Hospital approved the study.
Provenance and peer review Not commissioned; externally peer reviewed.