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Autoimmunizing mechanisms in thymoma and thymus
Nick Willcox1, Maria Isabel Leite, Yoshihisa Kadota
1Neuroscience Group, Weatherall Institute for Molecular Medicine, University of Oxford, England, UK. nick.willcox@imm.ox.ac.uk
Annals of the New York Academy of Sciences
|June 24, 2008
Summary
Investigating myasthenia gravis (MG) thymuses reveals thymic epithelial cells and myoid cells are implicated in autoimmunization. Complement deposition on these cells suggests a mechanism for autoimmune attack in MG, including seronegative generalized MG.
Area of Science:
- Immunology
- Autoimmune Diseases
- Thymus Research
Background:
- Studying human autoimmune mechanisms is challenging.
- Myasthenia gravis (MG) offers insights via thymus abnormalities.
- A hypothesis suggests thymic epithelial cells (TEC) initiate autoimmunity against acetylcholine receptors (AChR).
Purpose of the Study:
- To investigate the roles of thymic epithelial cells (TEC) and myoid cells in the autoimmune processes of myasthenia gravis (MG).
- To explore the involvement of complement system components in thymic autoimmunity.
- To examine similarities between seropositive and seronegative generalized MG (SNMG) patients.
Main Methods:
- Analysis of thymomas and hyperplastic MG thymuses.
- Focus on immune cell interactions and autoantibody targets like IFN-alpha and AChR.
- Examination of complement receptor expression and complement component deposition (C3b, membrane attack complex) on thymic cells.
Main Results:
- Hyperplastic MG thymuses show complement receptor upregulation on TEC and C3b deposition.
- Myoid cells in MG thymuses lack complement regulators, making them vulnerable.
- Complement component C3b and the membrane attack complex are deposited on myoid cells, particularly near germinal centers.
- Similar complement alterations are observed in seronegative generalized MG (SNMG) patients.
Conclusions:
- Both thymic epithelial cells (TEC) and myoid cells are implicated in the autoimmunization process in MG.
- Complement system activation and deposition on thymic cells contribute to MG pathogenesis.
- Findings support the inclusion of SNMG within the spectrum of AChR-seropositive MG.
- The study provides strong evidence supporting the multi-step hypothesis of autoimmunity in MG.
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