Myasthenia gravis thymus: complement vulnerability of epithelial and myoid cells, complement attack on them, and correlations with autoantibody status.

摘要: 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 myoid (with intact AChR) center formation. To test this, we screened for complement attack a wide range of typical generalized patients. Regardless exact serology, thymi sizeable unexpectedly showed patchy up-regulation both C5a terminal regulator CD59 on cells. These latter also deposits activated C3b component, which appeared even heavier infiltrating B cells, macrophages, especially follicular dendritic Myoid particularly vulnerable to complement; few expressed early regulators CD55, CD46, or CR1, none were detectably CD59+. Indeed, when exposed infiltrates, centers, frequently labeled C1q, (25 48%), C9, some showing obvious damage. This early/persistent strongly supports our hypothesis, implicating formation/autoantibody diversification. Remarkably, similar changes place many apparent AChR-seronegative patients same spectrum as AChR-seropositive