Single nucleotide polymorphisms in the interferon gamma gene are associated with distinct types of retinochoroidal scar lesions presumably caused by Toxoplasma gondii infection

The association of single nucleotide polymorphisms (SNPs) in the interferon (IFN)-γ gene ( IFNG ) with different types of retinal scar lesions presumably caused by toxoplasmosis were investigated in a cross-sectional population-based genetic study. Ten SNPs were investigated and after Bonferroni correction, only the associations between SNPs rs2069718 and rs3181035 with retinal/retinochoroidal scar lesions type A (most severe scar lesions) and C (least severe scar lesions), respectively, remained significant. The associations of two different IFNG SNPs with two different types of retinal lesions attributable to toxoplasmosis support the hypothesis that different inflammatory mechanisms underlie the development of these lesions. The in vitro analysis of IFN-γ secretion by peripheral blood mononuclear cells stimulated with Toxoplasma gondii antigens was also investigated. The association between SNP rs2069718 and type A scar lesions revealed that differential IFN-γ levels are correlated with distinct genotypes. However, no correlation was observed with IFN-γ secretion levels and the SNP rs3181035 , which was significantly associated with type C scar lesions. Our findings strongly suggest that immunogenetic studies of individuals with congenital or postnatally acquired infection are needed to better understand the role of IFN-γ and its polymorphisms in the pathogenesis of ocular toxoplasmosis.

Imunologia da retinocoroidite toxoplásmica / Immunology of the toxoplasmic retinochoroiditis

A infecção pelo Toxoplasma gondii é uma importante causa de doença ocular, tanto em indivíduos imunocomprometidos como em imunocompetentes. A patogênese da destruição retinocoroidiana associada a essa infecção ainda não está totalmente esclarecida. Nesta revisão, discute-se o papel do sistema imune no controle da infecção pelo Toxoplasma, especialmente, no olho.

Toxoplasma gondii infection is an important cause of ocular disease in both immunocompromised and immunocompetent subjects. The pathogenesis of retinochoroidal lesion associated with this infection is not fully understood. In this review, the role of the immune system in the control of Toxoplasma infection, especially in the eye, is discussed.

Toxoplasmose congênita em filho de mãe cronicamente infectada com reativação de retinocoroidite na gestação / Congenital toxoplasmosis from a chronically infected woman with reactivation of retinochoroiditis during pregnancy an underestimated event?

Objetivo: Apresentar um caso raro de toxoplasmose congênita de uma mãe imunocompetente com infecção crônica que teve reativação da doença ocular durante a gestação. Descrição: O recém-nascido estava assintomático no nascimento e foi identificado através de triagem neonatal (IgM anti-Toxoplasma gondii em sangue seco) entre outros 190 bebês com toxoplasmose congênita durante um período de 7 meses. Sua mãe tinha tido um episódio não tratado de reativação de retinocoroidite toxoplásmica durante a gestação, com títulos de IgG estáveis e resultados negativos para IgM. Os resultados de IgM e IgG no soro do recém-nascido e o teste de immunoblotting para IgG foram positivos, e detectou-se lesões retinocoroideanas ativas na periferia da retina. O recém-nascido foi tratado com sulfadiazina, pirimetamina e ácido folínico. Aos 14 meses de vida, a criança permanecia assintomática, com regressão das lesões retinocoroideanas e persistência de IgG. Comentários: É possível que a triagem neonatal sistemática em áreas com alta prevalência de infecção possa identificar esses casos.

Objectives: To report a rare case of congenital toxoplasmosis from an immunocompetent mother with chronic infection who had reactivation of ocular disease during pregnancy. Descriptions:The newborn was asymptomatic at birth and identified by neonatal screening (IgM anti-Toxoplasma gondii in dried blood) among other 190 infants with congenital toxoplasmosis during a 7-month period. His mother had had a non-treated episode of reactivation of toxoplasmic retinochoroiditis during pregnancy, with stable IgG titers and negative IgM results. Results of IgM and IgG in the newborn’s serum, as well as IgG immunoblotting were positive and active retinochoroidal lesions were detected in his peripheral retina. The neonate was treated with sulfadiazine, pyrimethamine and folinic acid. At 14 months of life, the child remained asymptomatic, with regression of retinochoroidal lesions and persistence of IgG. Comments: It is possible that systematic neonatal screening in areas with high prevalence of infection may identify these cases.

The IFN-γ +874T/A polymorphism is associated with retinochoroiditis toxoplasmosis susceptibility

Toxoplasmosis is a worldwide zoonosis that generally produces an asymptomatic infection. In some cases, however, toxoplasmosis infection can lead to ocular damage. The immune system has a crucial role in both the course of the infection and in the evolution of toxoplasmosis disease. In particular, IFN-γ plays an important role in resistance to toxoplasmosis. Polymorphisms in genes encoding cytokines have been shown to have an association with susceptibility to parasitic diseases. The aim of this work was to analyse the occurrence of polymorphisms in the gene encoding IFN-γ (+874T/A) among Toxoplasma gondii seropositive individuals, including those with ocular lesions caused by the parasite, from a rural population of Santa Rita de Cássia, Barra Mansa, state of Rio de Janeiro, Brazil. Further, we verified which of these polymorphisms could be related to susceptibility to the development of ocular toxoplasmosis. This study included 34 individuals with ocular toxoplasmosis (ocular group) and 134 without ocular lesions (control group). The differences between A and T allele distributions were not statistically significant between the two groups. However, we observed that a higher frequency of individuals from the ocular group possessed the A/A genotype, when compared with the control group, suggesting that homozygocity for the A allele could enhance susceptibility to ocular toxoplasmosis in T. gondii infection.

Immunopathology in ocular toxoplasmosis: facts and clues

Although parasite-mediated host cell lysis is deemed to be an important cause of tissue destruction in ocular toxoplasmosis (OT), the severity of the disease is probably correlated with hypersensitivity and inflammation. Notwithstanding, the mechanisms that regulate the inflammatory process in recurrent OT are poorly understood. Recent evidence has identified interleukin (IL) 17 as a marker for disease severity. The ocular and cerebral presence of this cytokine is generally associated with the induction of autoimmune responses in the brain and the eye. Indeed, there are indications that autoimmunity may contribute to clinical variability in the activity of OT. IL-23, which induces the proliferation of IL-17-producing cells and IL-27, which is a counterplayer to IL-17, may regulate T(H)-1-cell-mediated responses in OT. The importance of these cytokines in experimental models of uveitis and encephalitis has been recently reported. CD25(+) regulatory T-cells may control the local inflammatory response and protect the host against collateral inflammatory tissue damage. The responses of these cells to OT may be suitably tailored to cope with either an acquired or a congenital aetiology. Knowledge relating to immunoreactivity in OT has grown impressively during the past few years. Its characteristic and variable features have been identified and the potential relevance of autoimmunity has been assessed. In light of this knowledge, potential future treatment options have been considered.

Host immune response to Toxoplasma gondii and Ascaris lumbricoides in a highly endemic area: evidence of parasite co-immunomodulation properties influencing the outcome of both infections

Toxoplasmosis and ascaridiasis evoke polar Th-1 and Th-2 host immune responses, respectively. A study to investigate the specific cytokine profile production by in vitro cultures of peripheral blood mononuclear cells from individuals living under precarious sanitary conditions in a highly endemic area for the parasites Toxoplasma gondii and Ascaris lumbricoides was conducted. High levels of both IFN-³ (Th-1) and IL-13 (Th-2) were observed in groups of co-infected individuals presenting toxoplasmic ocular lesions. Significantly lower IL-10 and TGF-² levels were produced by co-infected individuals in comparison with groups of individuals not infected with A. lumbricoides and either positive or negative for T. gondii living under good sanitary conditions (control groups). The possible influence of co-parasitism on the clinical presentation of ocular toxoplasmosis is discussed.

Bilateral acute acquired toxoplasmic retinochoroiditis after steroid therapy for hantavirus pulmonary syndrome: case report

Description of a case of acute acquired ocular toxoplasmosis following hantavirus pulmonary syndrome. A 41-year-old man presenting hantavirus pulmonary syndrome, confirmed in the laboratory by detection of IgM antibodies to the virus, was submitted to high doses of intravenous corticosteroids for two months. After clinical improvement of hantavirus pulmonary syndrome the patient presented visual loss in both eyes that was secondary to a toxoplasmosis retinitis. The retinitis resolved with anti-toxoplasma therapy. Acquired toxoplasmic retinochoroiditis can occur following steroid therapy for hantavirus pulmonary syndrome.

Descrição de um caso de toxoplasmose ocular adquirida pós-síndrome pulmonar por hantavírus. Paciente com 41 anos do sexo masculino apresentando síndrome pulmonar por hantavírus, confirmado no laboratório pela detecção de anticorpos IGM para o vírus, foi submetido a altas doses de corticosteróides intravenosos durante dois meses. Após melhora clínica da síndrome pulmonar por hantavírus, apresentou perda visual em ambos os olhos secundária a retinite por toxoplasmose confirmada com sorologia (IGG e IGM positivo) A retinite resolveu após terapia sistêmica específica. A retinite por toxoplasmose pode ocorrer após terapia sistêmica com esteróide para síndrome pulmonar por hantavírus.

Toxoplasmosis retinochoroiditis after photodynamic therapy and intravitreal triamcinolone for a supposed choroidal neovascularization: a case report

The purpose is to report a complication after photodynamic therapy (PDT) and intravitreal triamcinolone for a presumed choroidal neovascularization in age-related macular degeneration. Photodynamic therapy and intravitreal triamcinolone were used in an 84-year-old man with choroidal neovascularization in the left eye. Forty-five days after therapy, the patient returned with a severe necrotizing uveitis in the posterior pole and vitritis. Laboratory investigation disclosed a high anti-Toxoplasma IgG titer. Therapy with pyrimethamine, sulfadiazine and folinic acid resulted in total lesion healing although central vision was lost. Intravitreal triamcinolone may have had an influence on the exacerbation of retinochoroiditis in the posterior pole of the patient. Although rare, this complication may not be disregarded in the cases that require intraocular corticosteroids for treatment of several conditions, especially in patients who had previously suffered from toxoplasmosis infection.

O objetivo é relatar complicação após terapia fotodinâmica (PDT) e triancinolona intravítrea para presumida neovascularização de coróide em degeneração macular relacionada à idade. A terapia fotodinâmica e triancinolona intravítrea foram utilizados em paciente de 84 anos, do sexo masculino, com neovascularização de coróide no olho esquerdo. Quarenta e cinco dias após o tratamento, o paciente retornou com grave retinite necrosante do pólo posterior e vitreíte. Investigação laboratorial indicou alto título de IgG anti-Toxoplasma. Tratamento com pirimetamina, sulfadiazina e ácido folínico levaram à total cicatrização da lesão embora a visão central tenha sido comprometida. Conclui-se que a triancinolona intravítrea pode ter influenciado na exacerbação da retinocoroidite no pólo posterior do paciente. Embora rara, esta complicação não pode ser descartada nos casos que necessitem corticóide intra-ocular para tratamento de várias doenças, principalmente em pacientes que tenham tido surtos prévios de toxoplasmose ocular.

Pesquisa de anticorpos anti Toxoplasma gondii em fluidos intra-oculares (humor vítreo e humor aquoso) de pacientes com toxoplasmose ocular, na cidade de Belém, PA / Research on antibodies anti toxoplasma gondii in intraocular fluids (Aqueous and vitreous humor) from patients with ocular toxoplasmosis, in the City of Belém, Pará State

Foi realizada pesquisa de anticorpos IgG, IgM e IgA anti-Toxoplasma gondii no soro e fluidos intra-oculares (humor aquoso e vítreo) de pacientes com toxoplasmose ocular. A partir dos resultados obtidos verificou-se que anticorpos IgG e IgA intraocular anti-Toxoplasma gondii podem vir a ser importantes marcadores no diagnóstico de toxoplasmose ocular.

Frequency of specific anti-Toxoplasma gondii IgM, IgA and IgE in Colombian patients with acute and chronic ocular toxoplasmosis

We studied the frequency of specific anti-Toxoplasma IgM, IgA and IgE antibodies in serum of 28 immunocompetent Colombian patients, selected by ophthalmologists and with lesions that were compatible with ocular toxoplasmosis. Patients were classified in three groups: (i) group 1 consisted of ten patients with a first episode; (ii) group 2, with seven patients with a recurrence and (iii) group 3, consisted of eleven patients with chronic chorioretinal lesion without uveitis. We found that 10/28 (35 per cent) of Colombian patients with ocular toxoplasmosis possessed at least one serological marker for Toxoplasma infection different from IgG. In group 1 (first episode), we found simultaneous presence of specific IgM plus IgA plus IgE in 1/10 (10 per cent). In group 2 (recurrences) in 1/7 (14 per cent) we found IgM and IgA test positives and in 1/7 (14 per cent) we found IgM and IgE tests positives. In group 3 (toxoplasmic chorioretinal scar) the IgA serological test was positive in 2/11 (18 per cent). These results show that serum IgM or IgA or IgE can be present during recurrences.

Value of estimating intraocular antiboddy production in diagnosi of typical and atypical lesions of ocular toxoplasmosis

Serum and aqueous humor [AH] samples were collected from 45 patients: 20 with typically active or reactivated retinal lesions of Toxoplasma [group I], 16 with atypical lesions [group II] and 9 with old quiescent scars [group III]. Also, serum and AH samples were collected from 10 patients with chronic toxoplasmosis without any ocular manifestation [group IV]. T. gondii specific IgG, IgA and IgM antibodies were measured by ELISA in AH and serum and the intraocular [local] antibody production was determined by calculating Goldman- Witmer coefficient [GWC]. IgG antibodies were the only class detected in all sera of patients with ocular and nonocular toxoplasmosis. An intraocular IgG antibody synthesis was confirmed in 95% and 37.5% of patients with typical [group I] and atypical [group II] posterior uveitis, respectively, and in no one of either patients with quiescent scars [group III] or the ophthalmologically free patients [group IV]. As regards the typical active lesions, the sensitivity of the IgG assay [95%] was higher than that of IgA [60%] and IgM [5%] assays

Evaluación oftalmológica e inmunodiagnóstica seriada de la retinocoroiditis toxoplasmosica Oftalmologic and series inmunodiagnostic evaluation of the toxoplasmosica retinochoroiditis / Oftalmologic and series inmunodiagnostic evaluation of the toxoplasmosic retinochoroiditis

Se diseño un estudio descriptivo y de seguimiento de las alternativas oftalmológicas, en asociación con la respuesta inmunológica en 107 pacientes con edades comprendidas entre 18 meses y 79 años, referidos a la Sección de Inmunodiagnóstico del Instituto de Medicina Tropical de la Facultad de Medicina de la Universidad Central de Venezuela entre junio 1994 y octubre 1995. El 54,2 de los pacientes se encontró en el grupo con mayor probabilidad clínica de presentar Toxoplasmosis ocular y en todos ellos se confirmaron títulos séricos positivos del IgG. El motivo de consulta más frecuente fue la disminución de la agudeza visual. No se encontró correlación entre la respuesta inmunoserológica dependiente de IgM y el grado de actividad de la lesión retinocoroidial. Se destaca la importancia de la evaluación oftalmológica seriada como elemento clave para iniciar el tratamiento ante lesiones activas

Toxoplamose ocular: aspectos imunologicos / Ocular toxoplasmosis: immunological aspects

A toxoplasmose, protozoose comum e benigna, assume eventualmente carater grave. O olho e um importante orgao-alvo do toxoplasma, sendo a retina frequente reservatorio de cistos de toxoplasma gondii. Assim, embora o quadro sistemico seja geralmente assintomatico, a toxoplamose e responsavel por 50 por cento dos casos de uveite no Brasil, sendo importante causa de cegueira. Em adicao, com o crescimento do numero de pessoas com SIDA e, por consequencia de pacientes com encefalite toxoplasmica, o estudo da toxoplasmose vem se tornando cada vez mais relevante...

Toxoplasma infection in healthy persons and in patients with HIV or ocular disease.

Toxoplasma infection is associated with acquired immune deficiency syndrome (AIDS), pregnancy, chorioretinitis, etc. Since the number of AIDS patients is increasing rapidly in Thailand and there are few reports about T. gondii immune status in this country. Toxoplasma-specific IgG and IgM antibodies (Ab) were determined in healthy persons and patients with different symptoms who were suspected of toxoplasmosis. Specific IgG Ab were detected in 3.2% of healthy persons, 12.5% of patients with ocular disease and in 42.5% in HIV positive patients. Only 3.1% of patients with ocular disease were positive for specific IgM Ab. No specific IgM Ab were found in the other samples studied.

Toxoplasmosis ocular en pacientes inmunocomprometidos y con síndrome de inmunodeficiencia adquirida: revisión bibliográfica / Ocular toxoplasmosis in immunocomprised and AIDS patients: bibliographic review

Debido a la creciente importancia de las infecciones oportunistas por toxoplasma gondii en diferentes estados de deficiencia inmunitaria, se dan a conocer algunos aspectos importantes publicados en la literatura universal, sobre toxoplasmosis ocular en este tipo de pacientes, especialmente aquellos infectados con el virus de inmunodeficiencia humana (VIH). Casos de retinocoroiditis toxoplásmica destructiva, con pérdida total de la visión, fueron observados en pacientes inmunocomprometidos tratados con corticoides a dosis altas. La experiencia con la toxoplasmosis ocular en pacientes infectados con el VIH es aún limitada y su frecuencia no ha podido establecerse con certeza. Sin embargo, se considera que la toxoplasmosis ocuparía el segundo lugar en frecuencia e importancia de la retinitis en los pacientes con SIDA, por lo que debería considerarse en estos casos, junto a la infección por CMV, en el diagnóstico diferencial de las retinitis extensas. Las lesiones oculares pueden aparecer como la primera manifestación de la toxoplasmosis, conjuntamente o a continuación de una encefalitis por T. gondii. Además, se observaron casos en que el diagnóstico de la toxoplasmosis ocular precedió el del SIDA. Las lesiones retinales son extensas y causan serio deterioro de la agudeza visual. El reconocimiento precoz del agente infeccioso oportunista, a través de exámenes de laboratorio, es de vital importancia, ya que se ha demostrado que la toxoplasmosis ocular en pacientes con SIDA responde favorablemente al tratamiento específico, si se inicia en forma precoz y se mantiene de por vida. Con respecto al origen de la toxoplasmosis ocular en el SIDA, no existe consenso. Algunos casos podrían corresponder a infecciones toxoplásmicas recientes; sin embargo, no se puede descartar la aparición de reactivaciones a nivel del ojo

Reaçöes de imunofluorescência indireta e de ELISA na detecçäo de anticorpos IgG e IgM, no soro de pacientes portadores de retinocoroidite ativa e cicatrizada supostamente toxoplásmica / Indirect imunofluorescence reactions and ELISA in detection of IgG and IgM antibodies in the serum of patients having active or healed retinochoroiditis assumed to be toxoplasmic

Este estudo baseia-se em 2 grupos: grupo-caso, constituido de 40 pacientes e grupo-controle de 18 pacientes. O grupo-caso corresponde a pacientes, portadores de lesöes de retinocoroidite ativa, supostamente toxoplasmática, enquanto que o grupo-controle é constituido de pacientes, com lesöes de retinocoroidites cicatrizadas, supostamente toxoplásmicas. Em ambos os grupos, foi estudado o soro dos pacientes para a detecçäo de anticorpos anti-T-gondii (IgG e IgM) nas técnicas de reaçäo de Imunofluorescência indireta e reaçäo imunoenzimática (ELISA). Os resultados obtidos revelam que ambas as técnicas, possuem a mesma sensibilidade e especificidade e que, a incidência de anticorpos IgM no grupo-caso para ELISA, foi de 12,5// e no grupo controle de 11,2

Imunoglobulinas e anti-corpos específicos IgG-IgM para T.Gondii no soro e no humor aquoso / Immunoglobulines and specific antibodies IgG-IgM in T.Gondii in aqueous humor and serum

No humor aquoso de pacientes com uveite posterior ativa (25 pacientes) foi encontrada uma concentraçäo de imunoglobulinas significativamente maior do que em pacientes com catarata senil (10 pacientes). No humor aquoso de mais de 90% de pacientes portadores de uveite, foram detectados anticorpos anti-T. gondii, enquanto que nos pacientes com catarata isto näo ocorreu em nenhum. Näo houve diferença significativa entre os títulos de anticorpos anti-T. gondii, detectados pela reaçäo de imunofluorescencia indireta, no soro dos pacientes com uveite e dos com catarata. A reaçäo de imunofluorescência indireta para toxoplasmose, realizada com conjugado anti-IgM, foi quase sempre negativa, näo tendo colaborado para o esclarecimento diagnóstico dos casos

Controvérsias sobre a fisiopatogenia da toxoplasmose ocular / Controversy on the physiopathogeny of ocular toxoplasmosis

Este trabalho tem como objetivo, abrir uma discussäo entre os resultados obtidos por vários autores, em relaçäo as reaçöes sorológicas para Toxoplasma gondii. A preocupaçäo dos autores foi o estudo da pesquisa de anti-corpos IgG e IgM anti-T. gondii, pelas técnicas de Elisa e Imunofluorescência Indireta, quer no soro como no humor aquoso, em pacientes portadores de uveíte posterior focal, granulomatosa e necrótica (supostamente toxoplásmica)