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Myasthenia gravis thymus: complement vulnerability of epithelial and myoid cells, complement attack on them, and correlations with autoantibody status.
- Source :
-
The American journal of pathology [Am J Pathol] 2007 Sep; Vol. 171 (3), pp. 893-905. Date of Electronic Publication: 2007 Aug 03. - Publication Year :
- 2007
-
Abstract
- In early-onset myasthenia gravis, the thymus contains lymph node-type infiltrates with frequent acetylcholine receptor (AChR)-specific germinal centers. Our recent evidence/two-step hypothesis implicates hyperplastic medullary thymic epithelial cells (expressing isolated AChR subunits) in provoking infiltration and thymic myoid cells (with intact AChR) in germinal center formation. To test this, we screened for complement attack in a wide range of typical generalized myasthenia patients. Regardless of the exact serology, thymi with sizeable infiltrates unexpectedly showed patchy up-regulation of both C5a receptor and terminal complement regulator CD59 on hyperplastic epithelial cells. These latter also showed deposits of activated C3b complement component, which appeared even heavier on infiltrating B cells, macrophages, and especially follicular dendritic cells. Myoid cells appeared particularly vulnerable to complement; few expressed the early complement regulators CD55, CD46, or CR1, and none were detectably CD59(+). Indeed, when exposed to infiltrates, and especially to germinal centers, myoid cells frequently labeled for C1q, C3b (25 to 48%), or even the terminal C9, with some showing obvious damage. This early/persistent complement attack on both epithelial and myoid cells strongly supports our hypothesis, especially implicating exposed myoid cells in germinal center formation/autoantibody diversification. Remarkably, the similar changes place many apparent AChR-seronegative patients in the same spectrum as the AChR-seropositive patients.
- Subjects :
- Animals
Antigens, CD metabolism
Autoantibodies immunology
Epithelial Cells cytology
Epithelial Cells pathology
Humans
Myasthenia Gravis pathology
Receptors, Complement metabolism
Autoantibodies blood
Complement System Proteins metabolism
Epithelial Cells immunology
Myasthenia Gravis immunology
Thymus Gland cytology
Thymus Gland immunology
Thymus Gland pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9440
- Volume :
- 171
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 17675582
- Full Text :
- https://doi.org/10.2353/ajpath.2007.070240