The involvement of autoimmunity against retinal antigens in determining disease severity in toxoplasmosis q Adriana Lima Vallochi a, * , Lı´lia da Silva Rios a , Marceli Vicente Nakamura a , Cla´udio Silveira b , Cristina Muccioli b , Maria Cristina Martins b , Rubens Belfort b , Luiz Vicente Rizzo a,c,d,e a Department of Immunology, Instituto de Cieˆncias Biome ´dicas, Universidade de Sa ˜o Paulo, Av Prof Lineu Prestes 1730, Sa ˜o Paulo, Brazil b Department of Ophthalmology, Escola Paulista de Medicina, Universidade Federal de Sa ˜o Paulo, Sa ˜o Paulo, Brazil c Fundac ¸a ˜o Zerbini, Sa ˜o Paulo, Brazil d LIM-60, Division of Allergy and Clinical Immunology, University of Sa ˜o Paulo Medical School, Universidade de Sa ˜o Paulo, Sa ˜o Paulo, Brazil e iii, Instituto de Investigac ¸a ˜o em Imunologia, Institutos do Mileˆnio, Ministe ´rio da Cieˆncia e Tecnologia, Brazil Received 28 May 2004; revised 4 November 2004; accepted 10 November 2004 Abstract Purpose: Ocular lesions are frequent in various individuals infected with Toxoplasma gondii. Disease intensity in ocular toxoplasmosis varies greatly between patients. Autoimmunity has been suggested as a possible component to retinal destruction. Methods: Immunologic parameters in the response to retina antigens were evaluated in infected persons with and without ocular lesions and in non-infected controls. Subjects were divided into groups on the basis of titers of serum antibodies to T. gondii, presence and severity of ocular lesions, and clinical history. Results: Peripheral blood mononuclear cells from patients with mild disease responded to one or more retinal antigens with a significantly higher frequency than patients without disease or with severe disease. Interestingly, the cytokines produced by the proliferating mononuclear cells did not follow any specific patterns, except for the fact that IL-4 and IL-5 were seldom detected. Conclusions: Our results suggest that although the presence of an immune response towards autoantigens is not protective against the development of ocular lesions by the T. gondii, it may protect against the development of severe disease. Ó 2004 Elsevier Ltd. All rights reserved. Keywords: Autoimmunity; IRBP; Ocular toxoplasmosis; Retinal antigens; S-Ag; Toxoplasma gondii 1. Introduction Toxoplasma gondii is a cosmopolitan parasite that infects more than two billion people worldwide [1]. The disease is often asymptomatic in the immunocompetent host but ocular lesions may be present in up to 20% of infected individuals [2e4]. Immunocompromised pa- tients infected with the parasite will often develop encephalitis and ocular lesions are also common in these individuals [5e8]. Necrotizing retinochoroiditis is the hallmark of ocular toxoplasmosis. It is commonly accompanied by anterior uveitis and vitreous inflammatory reaction. The typical q This work was supported in part by grants from Fundac¸a˜o de Amparo a Pesquisa do Estado de Sa˜o Paulo (FAPESP 98/11205-0 and 98/03906-9), the Pan-American Association of Ophthalmology (PAAO) and the Brazilian Ministry of Science and Technology (MCT) through the Millenium Institutes. LVR and RBJ are recipients of personal grants for scientific achievement from Conselho Nacional de Desenvolvimento Cintı´fico e Tecnolo´gico (CNPq) and ALV is a recipient of a post-doctoral fellowship from FAPESP, LSR is a recipient of a doctoral fellowship from FAPESP. * Corresponding author. Tel.: C55 11 3091 7430; fax: C55 11 3091 7394. E-mail address: vallochi@usp.br (A.L. Vallochi). 0896-8411/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.jaut.2004.11.003 Journal of Autoimmunity 24 (2005) 25e32 www.elsevier.com/locate/issn/08968411