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

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Abstract

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.

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Authors and Affiliations

  1. Unit Malattie Neuromuscolari, Dipartimento Medicina dei Sistemi, Università di Roma Tor Vergata, Rome, Italy

    Roberto Massa, Giulia Greco, Emanuele Rastelli, Chiara Terracciano & Erica Frezza

  2. Unit Genetica Medica, Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy

    Manuela Testi

  3. Neurofisiopatologia, Dipartimento NESMOS, Ospedale S. Andrea, Sapienza Università di Roma, Rome, Italy

    Matteo Garibaldi & Giovanni Antonini

  4. Neurologia, Dipartimento Medicina dei Sistemi, Università di Roma Tor Vergata, Rome, Italy

    Girolama A. Marfia & Nicola B. Mercuri

  5. Laboratorio d’Immunogenetica dei Trapianti, Dipartimento di Oncoematologia e Terapia Cellulare e Genica, IRCCS OPBG, Rome, Italy

    Franco Locatelli & Marco Andreani

  6. Dipartimento Chirurgia Toracica, Università di Roma Tor Vergata, Rome, Italy

    Eugenio Pompeo

Authors
  1. Roberto Massa
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  2. Giulia Greco
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  3. Manuela Testi
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  4. Emanuele Rastelli
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  7. Matteo Garibaldi
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  8. Girolama A. Marfia
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  9. Franco Locatelli
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  11. Eugenio Pompeo
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  12. Giovanni Antonini
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  13. Marco Andreani
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Corresponding author

Correspondence to Roberto Massa.

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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.

Additional information

Roberto Massa and Giulia Greco authors contributed equally to the work.

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Massa, R., Greco, G., Testi, M. et al. Thymomatous myasthenia gravis: novel association with HLA DQB1*05:01 and strengthened evidence of high clinical and serological severity. J Neurol 266, 982–989 (2019). https://doi.org/10.1007/s00415-019-09225-z

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  • DOI: https://doi.org/10.1007/s00415-019-09225-z

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