Thymomatous myasthenia gravis: novel association with HLA DQB1*05:01 and strengthened evidence of high clinical and serological severity

Roberto Massa, Giulia Greco, Manuela Testi, Emanuele Rastelli, Chiara Terracciano, Erica Frezza, Matteo Garibaldi, Girolama A Marfia, Franco Locatelli, Nicola B Mercuri, Eugenio Pompeo, Giovanni Antonini, Marco Andreani

Research output: Contribution to journalArticlepeer-review


BACKGROUND: The relative prevalence of myasthenia gravis (MG) subtypes is changing, and their differential features and association with HLA class II alleles are not completely understood.

METHODS: Age at onset, presence/absence of autoantibodies (Ab) and thymoma were retrospectively considered in 230 adult Italian patients. Clinical severity, assessed by MGFA scale, and the highest Ab titer were recorded. Furthermore, we performed low/high resolution typing of HLA-DRB1 and HLA-DQB1 alleles to detect associations of these loci with MG subtypes.

RESULTS: There were two peaks of incidence: under 41 years of age, with female preponderance, and over 60 years, with higher male prevalence. The former group decreased and the latter increased significantly when comparing onset period 2008-2015 to 2000-2007. Thymomatous (TMG) patients showed a higher prevalence of severe phenotype and significantly higher anti-AChR Ab titer than non-thymomatous (NTMG) patients. Among the latter, those with onset after 60 years of age (LO-NTMG) displayed significantly higher Ab titers but lower MGFA grade compared to early-onset patients (< 41 years; EO-NTMG). Significant associations were found between HLA DQB1*05:01 and TMG patients and between DQB1*05:02 and DRB1*16 alleles and LO-NTMG with anti-AChR Ab.

CONCLUSIONS: Two distinct cutoffs (< 41 and > 60 years) conveniently define EO-NTMG and LO-NTMG, with different characteristics. LO-NTMG is the most frequent disease subtype, with an increasing incidence. TMG patients reach higher clinical severity and higher antibody titers than NTMG patients. Moreover, TMG and LO-NTMG with anti-AChR Ab differ in their HLA-DQ association, providing further evidence that these two forms may have different etiologic mechanisms.

Original languageEnglish
Pages (from-to)982-989
Number of pages8
JournalJournal of Neurology
Issue number4
Publication statusPublished - Apr 2019


  • Adult
  • Age of Onset
  • Autoantibodies/blood
  • Female
  • Genetic Predisposition to Disease
  • HLA-DQ beta-Chains/genetics
  • Humans
  • Immunogenetic Phenomena
  • Incidence
  • Male
  • Middle Aged
  • Myasthenia Gravis/epidemiology
  • Prevalence
  • Retrospective Studies
  • Severity of Illness Index
  • Sex Factors
  • Thymoma/epidemiology
  • Thymus Neoplasms/epidemiology


Dive into the research topics of 'Thymomatous myasthenia gravis: novel association with HLA DQB1*05:01 and strengthened evidence of high clinical and serological severity'. Together they form a unique fingerprint.

Cite this