Insights into the classification of myasthenia gravis.

Masakatsu Motomura,Kazuo Fujihara,Shigeaki Suzuki,Yuriko Nagane,Akio Suzumura,Kimiaki Utsugisawa,Hiroyuki Murai,Takuhiro Yamaguchi,Tomihiro Imai,Masashi Aoki,Yasushi Suzuki,Tetsuya Akaishi

doi:10.1371/journal.pone.0106757

Abstract

Background and PurposeMyasthenia gravis (MG) is often categorized into thymoma-associated MG, early-onset MG with onset age <50 years, and late-onset MG with onset age ≥50 years. However, the boundary age of 50 years old between early- and late-onset MG remains controversial, and each category contains further subtypes. We attempted to classify MG from a statistical perspective.MethodsWe analyzed 640 consecutive MG patients using two-step cluster analysis with clinical variables and discrimination analysis, using onset age as a variable.ResultsTwo-step cluster analyses categorized MG patients into the following five subtypes: ocular MG; MG with thymic hyperplasia (THMG); generalized anti-acetylcholine receptor antibody (AChR-Ab)-negative MG; thymoma-associated MG; and generalized AChR-Ab-positive (SP) MG without thymic abnormalities. Among these 5 subtypes, THMG showed a distribution of onset age skewed toward a younger age (p<0.01), whereas ocular MG and SPMG without thymic abnormalities showed onset age skewed toward an older age (p<0.001 and p<0.0001, respectively). The other 2 subtypes showed normal distributions. THMG appeared as the main component of early-onset MG, and ocular MG and SPMG without thymic abnormalities as the main components of late-onset MG. Discrimination analyses between THMG and ocular MG and/or SPMG without thymic abnormalities demonstrated a boundary age of 45 years old.ConclusionsFrom a statistical perspective, the boundary age between early- and late-onset MG is about 45 years old.

Highlights

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against molecules in the neuromuscular junction (NMJ), such as anti-acetylcholine receptor antibody (AChR-Ab) or anti-muscle-specific receptor tyrosine kinase antibody (MuSK-Ab) [1]
Clinical factors The following clinical factors were used as variables: sex; age at onset; disease duration; presence of thymoma; presence of thymic hyperplasia; positivity for AChR-Ab or MuSK-Ab; positivities for other concurrent autoantibodies; MG Foundation of America (MGFA) clinical classification [7]; and MGFA postintervention status (MGFA-PIS) as the current outcome [7]
Two-step cluster analysis was performed for the data excluding ocular MG, and suggested separations of THMG (n = 100) and generalized AChR-Ab-negative MG (n = 90) with ‘‘fair’’ cluster quality

Summary

Introduction

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against molecules in the neuromuscular junction (NMJ), such as anti-acetylcholine receptor antibody (AChR-Ab) or anti-muscle-specific receptor tyrosine kinase antibody (MuSK-Ab) [1]. Each of these autoantibodies leads to distinct clinical characteristics [1]. MG is often classified as follows based on the thymic abnormalities present and age at onset: thymoma-associated MG (TAMG); early-onset MG with age at onset ,50 years; and late-onset MG with age at onset $50 years [3,4,5]. The boundary age of 50 years old between early- and late-onset MG remains controversial, and each category contains further subtypes.

Methods

Results

Conclusion