RESUMO
Ocular toxoplasmosis (OT) is characterised by intraocular inflammation due to Toxoplasma gondii infection. Studies have found that interleukin 17 (IL-17) plays a central role in the pathology of OT. However, nucleotide variability in IL17 and interleukin 17 receptor (IL17R) genes has not been characterised in OT. As cytokine gene polymorphisms may influence the expression of these molecules, the aim of this study was to verify whether IL17A (rs2275913), IL17F (rs763780), IL17RA (rs4819554) and IL17RC (rs708567) polymorphisms are associated with OT in a Brazilian population. This study enrolled 214 patients seropositive for T. gondii (110 with OT and 104 without) and 107 controls. Polymorphisms were identified by PCR-restriction fragment length polymorphism analysis, validated by DNA sequencing with chi-square and multivariate analyses being used to assess possible associations between polymorphisms and OT. Logistic regression under the dominant model revealed a protection factor against OT of the C mutant allele of the IL17F (rs763780) polymorphism. The T/C-C/C genotypes were significantly more common in patients without OT compared to those with OT (p value = 0.0066) and controls (p value = 0.014). Findings from this study suggest that the IL17F polymorphism may have an influence in the immunopathology of OT in Brazilian individuals.
Assuntos
Interleucina-17 , Toxoplasmose Ocular , Humanos , Toxoplasmose Ocular/genética , Toxoplasmose Ocular/imunologia , Toxoplasmose Ocular/parasitologia , Masculino , Feminino , Interleucina-17/genética , Adulto , Brasil , Pessoa de Meia-Idade , Adulto Jovem , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Polimorfismo de Fragmento de Restrição , Fatores de Proteção , Adolescente , Genótipo , Polimorfismo Genético , Reação em Cadeia da Polimerase , IdosoRESUMO
Toxoplasma gondii infection can trigger autoreactivity by different mechanisms. In the case of ocular toxoplasmosis, disruption of the blood-retinal barrier may cause exposure of confined retinal antigens such as recoverin. Besides, cross-reactivity can be induced by molecular mimicry of parasite antigens like HSP70, which shares 76% identity with the human ortholog. Autoreactivity can be a determining factor of clinical manifestations in the eye and in the central nervous system. We performed a prospective observational study to determine the presence of autoantibodies against recoverin and HSP70 by indirect ELISA in the serum of 65 patients with ocular, neuro-ophthalmic and congenital cerebral toxoplasmosis. We found systemic autoantibodies against recoverin and HSP70 in 33.8% and 15.6% of individuals, respectively. The presence of autoantibodies in cases of OT may be related to the severity of clinical manifestations, while in cases with CNS involvement they may have a protective role. Unexpectedly, anti-recoverin antibodies were found in patients with cerebral involvement, without ocular toxoplasmosis; therefore, we analyzed and proved cross-reactivity between recoverin and a brain antigen, hippocalcin, so the immunological phenomenon occurring in one immune-privileged organ (e.g. the central nervous system) could affect the environment of another (egg. the eye).
Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Interações Hospedeiro-Parasita/imunologia , Toxoplasmose Cerebral/imunologia , Toxoplasmose Congênita/imunologia , Toxoplasmose Ocular/imunologia , Adolescente , Adulto , Sequência de Aminoácidos , Antígenos de Protozoários/imunologia , Criança , Pré-Escolar , Reações Cruzadas/imunologia , Feminino , Proteínas de Choque Térmico HSP70/química , Proteínas de Choque Térmico HSP70/imunologia , Hipocalcina/química , Hipocalcina/imunologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Recoverina/química , Recoverina/imunologia , Toxoplasma/imunologia , Toxoplasmose Cerebral/diagnóstico , Toxoplasmose Cerebral/parasitologia , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/parasitologia , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/parasitologia , Adulto JovemRESUMO
DUSN is an infectious ocular disease that can lead to severe visual impairment and blindness. It usually occurs in young healthy individuals and depending on the stage of the disease, clinical presentation may range from mild vitritis and multifocal gray-white lesions in outer retina to optic atrophy.Parasites of different sizes and species have been proposed as the etiological agent of this disease. Thus, it is hypothesized that different infectious worms may be considered as the likely cause of a both autoimmune and toxic form of nematode retinopathy.Most patients present with already severe visual impairment and in the later stages of the disease, where the likelihood of improvement is low, despite therapy. In cases of early diagnosis, prompt treatment, whether with oral antihelmintic or direct photocoagulation of the worm, patients may show considerable visual improvement and have a more favorable prognosis.
Assuntos
Infecções Oculares Parasitárias/complicações , Granuloma/complicações , Macula Lutea/patologia , Retinite/etiologia , Toxoplasma/isolamento & purificação , Toxoplasmose Ocular/complicações , Acuidade Visual , Adolescente , Diagnóstico Diferencial , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/parasitologia , Angiofluoresceinografia/métodos , Fundo de Olho , Granuloma/diagnóstico , Granuloma/parasitologia , Humanos , Macula Lutea/parasitologia , Masculino , Retinite/diagnóstico , Retinite/parasitologia , Tomografia de Coerência Óptica , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/parasitologiaRESUMO
Peripheral blood mononuclear cells (PBMC) from patients with ocular toxoplasmosis were challenged with total antigens from Toxoplasma gondii lysate (TATL) in a cytokine release assay (CRA), run during the inactive period of the disease. Increased interferon gamma (IFN-γ) levels were detected after PBMC stimulation with either ME49 reference strain (P = 0.0015) or local TgCkAr-11-9 isolate (P = 0.0012), as compared with those recorded under basal conditions. TATL from TgCkAr11-9 isolate induced a higher release of IFN-γ than ME49 strain in CRA from all tested patients (P = 0.02). The median value of IFN-γ release on TgCkAr-11-9 stimulation (26.03 pg/mL) allowed the classification of patients into high- or low-/non-IFN-γ releasers. Clinical correlations were established with both groups. The results obtained in this study suggest the need to include local strains when performing CRA with TATL.
Assuntos
Interferon gama/sangue , Interleucina-10/sangue , Toxoplasma/imunologia , Toxoplasmose Ocular/imunologia , Adulto , Idoso , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Toxoplasmose Ocular/parasitologia , Adulto JovemRESUMO
INTRODUCTION: Toxoplasma gondii is a widely distributed parasite and of great importance to human and animal health. METHODS: The objective of this study was to assess the prevalence of T. gondii antibodies and risk factors associated with the infection in sheep in the Northwest region of the State of Rio Grande do Sul, Brazil; this region has a very high rate of human ocular toxoplasmosis. Ovine sera were tested by the modified agglutination test (cut-off 1:25). RESULTS: T. gondii antibodies were detected in 70.2% (224 of 319). According to the logistic regression, the most significant factors associated were age and cat access to food stock facility. CONCLUSION: Preventive measures are discussed to reduce the risk of transmission of this zoonosis.
Assuntos
Doenças dos Ovinos/epidemiologia , Toxoplasmose Animal/epidemiologia , Toxoplasmose Ocular/veterinária , Testes de Aglutinação , Animais , Anticorpos Antiprotozoários/sangue , Brasil/epidemiologia , Doenças Endêmicas/economia , Doenças Endêmicas/estatística & dados numéricos , Doenças Endêmicas/veterinária , Feminino , Masculino , Ovinos , Doenças dos Ovinos/sangue , Doenças dos Ovinos/parasitologia , Toxoplasma/imunologia , Toxoplasma/fisiologia , Toxoplasmose Animal/sangue , Toxoplasmose Animal/diagnóstico , Toxoplasmose Animal/parasitologia , Toxoplasmose Ocular/sangue , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/parasitologiaRESUMO
Ocular toxoplasmosis is one of the most common complications caused by the infection with the parasite Toxoplasma gondii. The risk of developing eye lesions and impaired vision is considered higher in Brazil than other countries. The clinical diagnosis is difficult and the use of sensitive and specific laboratorial methods can aid to the correct diagnosis of this infection. We compared serological methods ELISA and ELFA, and molecular cPCR, Nested PCR and qPCR for the diagnosis of T. gondii infection in groups of patients clinically evaluated with ocular diseases non-toxoplasma related (G1 = 185) and with lesions caused by toxoplasmosis (G2 = 164) in an Ophthalmology clinic in Brazil. Results were compared by the Kappa index, and sensitivity (S), specificity (E), positive predictive value (PPV), and negative (NPV) were calculated. Serologic methods were in agreement with ELISA more sensitive and ELFA more specific to characterize the acute and chronic infections while molecular methods were discrepant where qPCR presented higher sensitivity, however, lower specificity when compared to cPCR and Nested PCR.
Assuntos
Técnicas de Diagnóstico Molecular/métodos , Saúde Pública , Testes Sorológicos/métodos , Toxoplasma/genética , Toxoplasma/isolamento & purificação , Toxoplasmose Ocular/diagnóstico , Uveíte/diagnóstico , Anticorpos Antiprotozoários/sangue , Brasil , DNA de Protozoário/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Oftalmologia , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Toxoplasma/imunologia , Toxoplasmose Ocular/parasitologia , Uveíte/parasitologiaRESUMO
Purpose: The purpose of this article is to analyze possible associations between systemic and ocular cytokine levels and specific clinical ophthalmologic signs from patients with a reactivation of toxoplasmic retinochoroiditis (RTR). Methods: A total of 18 patients with an active RTR episode, 8 patients with inactive scars, and 14 control patients were included in the study. Serum samples and aqueous humor (AH) samples were analyzed for IFN (interferon)-γ, interleukin (IL)-10, and IL-6 levels by ELISA. Inflammation grade, location, and size of the retinochoroidal active lesion, sampling time, and time to resolution were recorded. Results: A significantly negative correlation between AH and serum levels of IFN-γ was detected (p < 0.05). Patients with an AH IFN-γ/IL-10 ratio lower than 1 were associated with the longest time to resolution and/or severe complications. Conclusion: Serum IFN-γ levels may be used as a prognostic marker for both time to resolution and the development of possible severe complications during a given RTR episode.
Assuntos
Biomarcadores/sangue , Coriorretinite/parasitologia , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Toxoplasma/fisiologia , Toxoplasmose Ocular/parasitologia , Adulto , Antiprotozoários/uso terapêutico , Humor Aquoso/metabolismo , Coriorretinite/tratamento farmacológico , Coriorretinite/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Fatores Imunológicos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Toxoplasmose Ocular/tratamento farmacológico , Toxoplasmose Ocular/imunologia , Adulto JovemRESUMO
INTRODUCTION: Cases of toxoplasmosis present in South America tend to be more severe than that found in other continents. Here, we present our clinical experience of ocular and ganglionar toxoplasmosis in the use of PCR, and of the treatment to prevent ocular involvement. METHODOLOGY: Retrospective analysis of clinical charts of patients with ocular and lymphadenitic toxoplasmosis at the parasitology and tropical medicine consultation in the "Universidad del Quindio" in Colombia. In total, 91 records of cases with ocular toxoplasmosis and 17 with lymphadenitis that underwent PCR analysis for B1 repeated sequence in blood, were compared to the results of 104 people with chronic asymptomatic toxoplasmosis. In addition, 41 clinical records were included from patients with confirmed toxoplasmic lymphadenitis: 10 untreated, 6 that begun treatment after four months of symptoms, and 25 that were treated during the first four months of symptoms and had a follow-up during at least one year. RESULTS: Patients with ocular toxoplasmosis or lymphadenitis had a higher probability of PCR positivity in peripheral blood than chronic asymptomatic people. There were no cases of retinochoroiditis in 25 patients with toxoplasmic lymphadenitis treated before 4 months of symptoms and followed during at least 12 months. In four out of ten untreated cases, new lesions of retinochoroiditis presented after the symptoms of lymphadenitis. CONCLUSIONS: Toxoplasmosisin South America exhibits different clinical behavior and this influences the laboratory results as well as the need for treatment in the case of lymphadenitis. Clinicians should be aware of the geographical origin of the infection in order to adopt different therapeutic and diagnostic approaches.
Assuntos
Cistos Glanglionares/parasitologia , Linfadenite/parasitologia , Reação em Cadeia da Polimerase/métodos , Toxoplasma/genética , Toxoplasma/isolamento & purificação , Toxoplasmose Ocular/parasitologia , Adulto , Colômbia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Toxoplasmose Ocular/epidemiologiaRESUMO
CC chemokine receptor type 5 (CCR5) is a chemokine receptor that influences the immune response to infectious and parasitic diseases. This study aimed to determine whether the CCR5Δ32 and CCR5 59029 A/G polymorphisms are associated with the development of ocular toxoplasmosis in humans. Patients with positive serology for Toxoplasma gondii were analyzed and grouped as 'with ocular toxoplasmosis' (G1: n=160) or 'without ocular toxoplasmosis' (G2: n=160). A control group (G3) consisted of 160 individuals with negative serology. The characterization of the CCR5Δ32 and CCR5 59029 A/G polymorphisms was by PCR and by PCR-RFLP, respectively. The difference between the groups with respect to the mean age (G1: mean age: 47.3, SD±19.3, median: 46 [range: 18-95]; G2: mean age: 61.3, SD±13.7, median: 61 [range: 21-87]; G3: mean age: 38.8, SD±17.9, median: 34 [range: 18-80]) was statistically significant (G1 vs.G2: p-value <0.0001; t=7.21; DF=318; G1 vs.G3: p-value <0.0001; t=4.32; DF=318; G2 vs. G3: p-value <0.0001; t=9.62; DF=318). The Nagelkerke r2 value was 0.040. There were statistically significant differences for the CCR5/CCR5 (p-value=0.008; OR=0.261), AA (p-value=0.007; OR=2.974) and AG genotypes (p-value=0.018; OR=2.447) between G1 and G2. Individuals with the CCR5/CCR5 genotype and simultaneously the CCR5-59029 AA or AG genotypes have a greater risk of developing ocular toxoplasmosis (4% greater), which may be associated with a strong and persistent inflammatory response in ocular tissue.
Assuntos
Predisposição Genética para Doença , Polimorfismo Genético , Receptores CCR5/genética , Toxoplasmose Ocular/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco , Toxoplasma , Toxoplasmose Ocular/parasitologia , Adulto JovemRESUMO
This study evaluated levels for mRNA expression of 7 cytokines in ocular toxoplasmosis. Peripheral blood mononuclear cells (PBMC) of patients with ocular toxoplasmosis (OT Group, n = 23) and chronic toxoplasmosis individuals (CHR Group, n = 9) were isolated and stimulated in vitro with T. gondii antigen. Negative controls (NC) were constituted of 7 PBMC samples from individuals seronegative for toxoplasmosis. mRNA expression for cytokines was determined by qPCR. Results showed a significant increase in mRNA levels from antigen stimulated PBMCs derived from OT Group for expressing IL-6 (at P < .005 and P < .0005 for CHR and NC groups, respectively), IL-10 (at P < .0005 and P < .005 for CHR and NC groups, respectively) and TGF-ß (at P < .005) for NC group. mRNA levels for TNF-α and IL-12 were also upregulated in patients with OT compared to CHR and NC individuals, although without statistical significance. Additionally, mRNA levels for IL-27 and IFN-γ in PBMC of patients with OT were upregulated in comparison with NC individuals. Differences between OT and NC groups were statistically significant at P < .05 and P < .0005, respectively.