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C. S. Specht, E. J. Rushing; Immunopathology of Sympathetic Uveitis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5192.
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Sympathetic uveitis (SU) is a rare, non-necrotizing autoimmune granulomatous uveitis that occurs in one eye after penetrating injury and can then affect the fellow eye. The AFIP files (1970-2005) were searched for enucleated eyes with SU, in order to study the immunopathology of this disorder in clinical cases.
All studies were done using formalin-fixed, paraffin-embedded tissue. Five cases of SU with paraffin blocks were identified. Two cases of ocular tuberculosis (OTB) were selected for comparison. Using standard methods, all seven cases were studied with immunohistochemistry for BAX, BCL-2, inducible nitric oxide synthase (iNOS), CD3, CD4, CD8, CD20, CD44, CD56, CD63, CD68, CD163, and with histochemistry using Wilder-Manuel reticulin and Masson trichrome stains.
The diffuse granulomatous reaction in SU consists of lymphocytes and histiocytes, and is confined to uveal tissue. The lymphocytes include CD3 (+) CD4 (+) and CD3 (+) CD8 (+) T-cells, and CD20 (+) B-cells; a variable number of CD44 (+) lymphocytes is seen. No CD56 (+) cells are identified. The lymphocytes in the OTB cases are similar. Histiocytes in SU are CD68 (+) and less often CD63 (+), with frequent expression of CD44 and CD163 indicating an activated phenotype. These histiocytes contain moderate levels of iNOS, moderate to high levels of BAX, and low levels of BCL-2. Some plasma cells are noted; scattered eosinophils are seen. There is moderate reticulin fibrosis. Histiocytes in OTB are phenotypically similar to those of SU, but express more iNOS and BAX, and less BCL-2. The necrotizing granulomas of OTB involve all ocular coats, mycobacteria are present, and reticulin fibrosis is severe.
These enucleated eyes with sympathetic uveitis (SU) show well-established diffuse granulomatous inflammation, with activated histiocytes and a Th1/Th2 immune balance that is shifted toward Th2. The level of iNOS expression and the BAX/BCL-2 balance in SU favors apoptosis of histiocytes. The immune balance in the enucleated eyes with ocular tuberculosis (OTB) is also shifted toward Th2, but the levels of iNOS, BAX, BCL-2, and reticulin fibrosis in these cases suggests a greater drive toward apoptosis and fibrosis in OTB.
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