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MIYAMOTO C, MATTOS NETO RB, ET AL. Graph 1. Immunohistochemistry expression of CD4, CD68 and CD25. Figure 3. Section of a ocular specimen in a case of toxoplasmosis showing the inflammatory infiltrate and positive immunohistochemical expression of CD4 ( X 400 magnification). better outcome. Considering that ocular toxoplasmosis is a recurrent disease, especially the congenital form (30) , having a method to distinguish both forms can be very useful, helping in treatment and also in the management with different prophylactic measures for recurrent lesions, for instance. Our findings suggest a possible laboratory tool to distinguish them. Figure 2. High magnification demonstrating the immunohistochemical expression of CD25 (in green) ( X 400 magnification). distinguish congenital from late acquired cases. Congenital cases are consistently IL-2 negative while acquired toxoplasmosis are positive. Our study is unique because we had enucleated eyes, so we chose to study the expression of CD25, which is the transmembrane protein of the receptor of IL-2. As expected, all confirmed acquired cases were positive for CD25. It is indeed impossible to determine whether the cases of patients IgM negative were congenital or late acquired ones. Interestingly, we saw that four patients were negative, while two were positive. Considering the previous findings of Yamamoto et al. (7) , it is plausible that in this pilot study we were able to distinguish acquired from congenital cases based on CD25 expression. Consequently, further studies comparing confirmed cases of congenital ocular toxoplasmosis to acquired ones are warranted to substantiate our conclusions. It has been suggested that the mechanisms involved in the development of ocular lesions may be different in the two forms of toxoplasmosis (congenital and acquired), despite the similarity in the pathological characteristics (7) . One hypothesis proposes that patients with congenital disease could have been T. gondii-specific T cells deleted or anergized through exposure to toxoplasma antigens during the prenatal period, which could explain the diminished response of T cells from patients with congenital disease (7) . If the mechanisms of response to ocular toxoplasmosis differs regarding it is congenital or acquired, it would be useful to have specific treatments for each one, in order to obtain a CONCLUSIONS High expression of CD25 was found exclusively in acquired cases of ocular toxoplasmosis. To the best of our knowledge, this is the first report showing that the use of CD25 as a marker for IL-2 is helpful to differentiate acquired ocular toxoplasmosis. It further supports the theory that the IL-2 signalling axis may differ between congenital and acquired cases of ocular toxoplasmosis. Our findings are important because they provide a laboratory tool that could be used to differentiate between acquired and congenital disease, and they may reinforce the hypothesis that the mechanisms involved in the development of ocular lesions may be different in the two forms of disease, despite the similarity in the pathologic features. REFERENCES 1. Silveira C, Belfort R Jr, Burnier M Jr, Nussenblatt R. Acquired toxoplasmic infection as the cause of toxoplasmic retinochoroiditis in families. Am J Ophthalmol. 1988; 106(3):362-4. 2. Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet 2004;363(9425):1965-76. Comment in: Lancet. 2004;364(9434):579. 3. Commodaro AG, Belfort RN, Rizzo LV, Muccioli C, Silveira C, Burnier Jr MN, et al. Ocular toxoplasmosis: an update and review of the literature. Mem Inst Oswaldo Cruz. 2009;104(2):345-50. 4. Perkins ES. Ocular toxoplasmosis. Bull Ophthalmol Soc Egypt. 1967;60(64):523-7. 5. Luft BJ, Brooks RG, Conley FK, McCabe RE, Remington JS. Toxoplasmic encephalitis in patients with acquired immune deficiency syndrome. JAMA. 1984;252(7):913-7. 6. Silveira C. Toxoplasmose: levantamento bibliográfico de 1997 a 2000. Arq Bras Oftalmol [Internet]2001[citado 2010 Set 18];64(3):263-70. Disponivel em: http:// www.scielo.br/pdf/abo/v64n3/12517. pdf 7. Yamamoto JH, Vallochi AL, Silveira C, Filho JK, Nussenblatt RB, Cunha-Neto, E, et al. Discrimination between patients with acquired toxoplasmosis and congenital toxoplasmosis on the basis of the immune response to parasite antigens. J Infect Dis. 2000;181(6):2018-22. 8. Sterkers Y, Varlet-Marie E, Marty P, Bastien P. Diversity and evolution of methods and practices for the molecular diagnosis of congenital toxoplasmosis in France: a four years survey. Clin Microbiol Infect. Forthcoming 2009. 9. Perkins ES. Ocular toxoplasmosis. Br J Ophthalmol. 1973;57(1):1-17. Arq Bras Oftalmol. 2010;73(5):443-6 445
USE OF CD25 AS AN IMMUNOHISTOCHEMICAL MARKER FOR ACQUIRED OCULAR TOXOPLASMOSIS 10. Saari M, Vuorre I, Neiminen H, Raisanen S. Acquired toxoplasmic chorioretinitis. Arch Ophthalmol. 1976;94(9):1485-8. 11. Glasner PD, Silveira C, Kruszon-Moran D, Martins MC, Burnier Junior M, Silveira S, et al. An unusually high prevalence of ocular toxoplasmosis in southern Brazil. Am J Ophthalmol. 1992;114(2):136-44. 12. Brézin AP, Egwuagu CE, Burnier M Jr, Silveira C, Mahdi RM, Gazzinelli RT, et al. Identification of Toxoplasma gondii in paraffin-embedded sections by the polymerase chain reaction. Am J Ophthalmol. 1990;110(6):599-604. 13. Montoya JG, Rosso F. Diagnosis and management of toxoplasmosis. Clin Perinatol. 2005;32(3):705-26. 14. Montoya JG, Remington JS. Toxoplasmic chorioretinitis in the setting of acute acquired toxoplasmosis. Clin Infect Dis. 1996;23(2):277-82. Comment in: Clin Infect Dis. 1997;24(4):745-6. 15. Liesenfeld O, Press C, Montoya JG, Gill R, Isaac-Renton JL, Hedman K, et al. Falsepositive results in immunoglobulin M (IgM) toxoplasma antibody tests and importance of confirmatory testing: the Platelia Toxo IgM test. J Clin Microbiol. 1997;35(1):174-8. 16. Silveira C, Belfort R Jr, Muccioli C, Abreu MT, Martins MC, Victgora C, et al. A follow-up study of Toxoplasma gondii infection in southern Brazil. Am J Ophthalmol. 2001; 131(3):351-4. 17. Melamed J. Contributions to the history of ocular toxoplasmosis in Southern Brazil. Mem Inst Oswaldo Cruz. 2009;104(2):358-63. 18. Turka LA, Walsh PT. IL-2 signaling and CD4+ CD25+ Foxp3+ regulatory T cells. Front Biosci. 2008;13:1440-6. 19. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995;155(3):1151-64. 20. Létourneau S, van Leeuwen EM, Krieg C, Martin C, Pantaleo G, Sprent J, et al. IL-2/anti- IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor alpha subunit CD25. Proc Natl Acad Sci USA. 2010;107(5): 2171-6. 21. Matos K, Muccioli C, Belfort Junior R, Rizzo LV. Correlation between clinical diagnosis and PCR analysis of serum, aqueous, and vitreous samples in patients with inflammatory eye disease. Arq Bras Oftalmol. 2007;70(1):109-14. 22. Rothova A. Ocular involvement in toxoplasmosis. Br J Ophthalmol. 1993;77(6):371-7. Erratum in: Br J Ophthalmol. 1993;77(10):683. 23. van der Veen J, Polak MF. Prevalence of toxoplasma antibodies according to age with comments on the risk of prenatal infection. J Hyg (Lond). 1980;85(2):165-74. 24. Rothova A, van Knapen F, Baarsma GS, Kruit PJ, Loewer-Sieger DH, Kijlstra A. Serology in ocular toxoplasmosis. Br J Ophthalmol. 1986;70(8):615-22. 25. Ongkosuwito JV, Bosch-Driessen EH, Kijlstra A, Rothova A. Serologic evaluation of patients with primary and recurrent ocular toxoplasmosis for evidence of recent infection. Am J Ophthalmol. 1999;128(4):407-12. 26. Belfort RN, Rasmussen S, Kherani A, Lodha N, Williams G, Fernandes BF, et al. Bilateral progressive necrotizing retinochoroiditis in an immunocompromised patient: histopathological diagnosis. Acta Ophthalmol. 2010;88(5):614-5. Comment in: Acta Ophthalmol. 2010;88(3):e92; author reply e93. 27. Rao NA, Font RL. Toxoplasmic retinochoroiditis: electron-microscopic and immunofluorescence studies of formalin-fixed tissue. Arch Ophthalmol. 1977;95(2):273-7. 28. Burg JL, Grover CM, Pouletty P, Boothroyd JC. Direct and sensitive detection of a pathogenic protozoan, Toxoplasma gondii, by polymerase chain reaction. J Clin Microbiol. 1989;27(8):1787-92. 29. Goncalves RM, Rodrigues DH, Camargos da Costa AM, Teixeira MM, Ribeiro Campos W, Órefice C, et al. Increased serum levels of CXCL8 chemokine in acute toxoplasmic retinochoroiditis. Acta Ophthalmol Scand. 2007;85:(8)871-6. 30. Vasconcelos-Santos DV, Machado Azevedo DO, Campos WR, Oréfice F, Queiroz-Andrade GM, Carellos EV, Castro Romanelli RM, Januário JN, Resende LM, Martins-Filho OA, de Aguiar Vasconcelos Carneiro AC, Almeida Vitor RW, Caiaffa WT; UFMG Congenital Toxoplasmosis Brazilian Group. Congenital toxoplasmosis in southeastern Brazil: results of early ophthalmologic examination of a large cohort of neonates. Ophthalmology. 2009;116(11): 2199-205 e1. VI Congresso Brasileiro de Catarata e Cirurgia Refrativa IV Simpósio Brasileiro de Administração em Oftalmologia I Congresso Internacional de Cirurgia Plástica Ocular 01 a 4 de junho de 2011 Porto de Galinhas - PE Informações: Site: www.catarata-refrativa.com.br/2011 446 Arq Bras Oftalmol. 2010;73(5):443-6
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