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

  • Roberto MassaEmail author
  • 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
Original Communication



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.


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.


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.


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.


Myasthenia gravis Disease subgroups Late-onset Early onset Thymoma HLA association 


Compliance with ethical standards

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standards

The study protocol was approved by the Independent Ethic Committee of PTV and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

All participating subjects signed an informed consent.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Roberto Massa
    • 1
    Email author
  • Giulia Greco
    • 1
  • Manuela Testi
    • 2
  • Emanuele Rastelli
    • 1
  • Chiara Terracciano
    • 1
  • Erica Frezza
    • 1
  • Matteo Garibaldi
    • 3
  • Girolama A. Marfia
    • 4
  • Franco Locatelli
    • 5
  • Nicola B. Mercuri
    • 4
  • Eugenio Pompeo
    • 6
  • Giovanni Antonini
    • 3
  • Marco Andreani
    • 5
  1. 1.Unit Malattie Neuromuscolari, Dipartimento Medicina dei SistemiUniversità di Roma Tor VergataRomeItaly
  2. 2.Unit Genetica MedicaAzienda Ospedaliera San Camillo-ForlaniniRomeItaly
  3. 3.Neurofisiopatologia, Dipartimento NESMOSOspedale S. Andrea, Sapienza Università di RomaRomeItaly
  4. 4.Neurologia, Dipartimento Medicina dei SistemiUniversità di Roma Tor VergataRomeItaly
  5. 5.Laboratorio d’Immunogenetica dei Trapianti, Dipartimento di Oncoematologia e Terapia Cellulare e GenicaIRCCS OPBGRomeItaly
  6. 6.Dipartimento Chirurgia ToracicaUniversità di Roma Tor VergataRomeItaly

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