Characterization of the thymus in Lrp4 myasthenia gravis: Four cases

Inga Koneczny, Dorit Rennspiess, Florit Marcuse, Nathalie Dankerlui, Myurgia Abdul Hamid, Marina Mane-Damas, Jos Maessen, Paul Van Schil, Abhishek Saxena, Paraskevi Zisimopoulou, Konstantinos Lazaridis, Mark Woodhall, Katerina Karagiorgou, John Tzartos, Socrates Tzartos, Marc H. De Baets, Peter C. Molenaar, Alexander Marx, Axel zur Hausen, Mario Losen*Pilar Martinez-Martinez*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

10 Citations (Web of Science)

Abstract

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Most patients have pathogenic autoantibodies against the acetylcholine receptor (AChR). In the last years a novel subpopulation of MG patients has been described that harbors antibodies against low-density lipoprotein receptor-related protein 4 (Lrp4), another postsynaptic neuromuscular antigen. In early-onset AChR MG (EOMG), the thymus plays an important role in immunopathogenesis, and early thymectomy is beneficial. It is still unknown if the thymus plays any role in Lrp4-MG. In this pilot study, we compared thymus samples from four patients with Lrp4-MG (one pre-treated with immunosuppressive drugs), four non-MG controls and five EOMG patients (not pretreated with immunosuppressive drugs). Immunohistochemistry of the Lrp4-MG thymi revealed normal architecture, with normal numbers and distribution of B-cells, lymphoid follicles and Hassall's corpuscles. Primary CD23(+) lymphoid follicles were similarly infrequent in Lrp4-MG and control thymic sections. In none of the control or Lrp4-MG thymi did we find secondary follicles with CD10(+) germinal centers. These were evident in 2 of the 5 EOMG thymi, where primary lymphoid follicles were also more frequent on average, thus showing considerable heterogeneity between patients. Even if characteristic pathological thymic changes were not observed in the Lrp4 subgroup, we cannot exclude a role for the thymus in Lrp4-MG pathogenesis, since one Lrp4-MG patient went into clinical remission after thymectomy alone (at one year followup) and one more improved after thymectomy in combination with immunosuppressive therapy.

Original languageEnglish
Pages (from-to)50-55
Number of pages6
JournalAutoimmunity Reviews
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 2019

Keywords

  • GERMINAL-CENTERS
  • MYOID CELLS
  • AUTOANTIBODIES
  • PATHOGENESIS
  • THYMECTOMY
  • MECHANISMS
  • EXPRESSION
  • ANTIBODIES
  • THERAPY
  • THYMOMA

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