Serum levels of neurotrophic factors in active toxoplasmic retinochoroiditis

Abstract Toxoplasmic retinochoroiditis (TR) is the most common identifiable cause of posterior uveitis in Brazil. Response to treatment and clinical presentation may vary significantly. We assessed serum levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin (NT)-3, and NT-4/5 in patients with active TR, before and after TR treatment. Methods: Twenty patients with active lesion and 15 healthy controls were enrolled in the study. Serum concentration of neurotrophic factors was determined by enzyme-linked immunosorbent assay. Results: BDNF levels were significantly higher in patients before treatment when compared with controls (p = 0.0015). There was no significant difference in pro-BDNF, NGF, GDNF, NT-3, and NT-4/5 levels between TR patients and controls. Treatment did not affect the levels of these factors. Conclusion: BDNF may be released in the context of the active TR inflammatory response.

Serum levels of neurotrophic factors in active toxoplasmic retinochoroiditis.

Toxoplasmic retinochoroiditis (TR) is the most common identifiable cause of posterior uveitis in Brazil. Response to treatment and clinical presentation may vary significantly. We assessed serum levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin (NT)-3, and NT-4/5 in patients with active TR, before and after TR treatment. METHODS: Twenty patients with active lesion and 15 healthy controls were enrolled in the study. Serum concentration of neurotrophic factors was determined by enzyme-linked immunosorbent assay. RESULTS: BDNF levels were significantly higher in patients before treatment when compared with controls (p=0.0015). There was no significant difference in pro-BDNF, NGF, GDNF, NT-3, and NT-4/5 levels between TR patients and controls. Treatment did not affect the levels of these factors. CONCLUSION: BDNF may be released in the context of the active TR inflammatory response.

Detection of Toxoplasma gondii DNA in peripheral blood and aqueous humor of patients with Toxoplasmic active focal necrotizing retinochoroiditis using real-time PCR.

PURPOSE: To evaluate the ability of real-time quantitative PCR (qPCR) for detectingToxoplasma gondii DNA in the peripheral blood and aqueous humor of patients with toxoplasmic active focal necrotizing retinochoroiditis. METHODS: Fifty-five patients with infectious uveitis seen from 2009 to 2013 at the Department of Ophthalmology and Visual Sciences of the Federal University of São Paulo were enrolled in this study. Forty-three patients had toxoplasmic active focal necrotizing retinochoroiditis, and the remaining 12 had non-toxoplasmic infectious uveitis and served as controls. qPCR analysis forT. gondii DNA was performed on the patients' peripheral blood and aqueous humor samples. RESULTS: The qPCR was positive for T. gondii DNA in 37.21% (16/43) of the aqueous humor samples and 2.33% (1/43) of the peripheral blood samples; further, 16.27% (7/43) of the patients had positive results in both their blood and aqueous humor samples. CONCLUSION: qPCR was able to detect T. gondii DNA in patients with toxoplasmic active focal necrotizing retinochoroiditis in the blood as well as the aqueous humor and can help with the diagnosis of the disease.

Detection of Toxoplasma gondii DNA in peripheral blood and aqueous humor of patients with Toxoplasmic active focal necrotizing retinochoroiditis using real-time PCR / Detecção de DNA do Toxoplasma gondii no sangue periférico e humor aquoso por PCR em tempo real

ABSTRACT Purpose: To evaluate the ability of real-time quantitative PCR (qPCR) for detectingToxoplasma gondii DNA in the peripheral blood and aqueous humor of patients with toxoplasmic active focal necrotizing retinochoroiditis. Methods: Fifty-five patients with infectious uveitis seen from 2009 to 2013 at the Department of Ophthalmology and Visual Sciences of the Federal University of São Paulo were enrolled in this study. Forty-three patients had toxoplasmic active focal necrotizing retinochoroiditis, and the remaining 12 had non-toxoplasmic infectious uveitis and served as controls. qPCR analysis forT. gondii DNA was performed on the patients' peripheral blood and aqueous humor samples. Results: The qPCR was positive for T. gondii DNA in 37.21% (16/43) of the aqueous humor samples and 2.33% (1/43) of the peripheral blood samples; further, 16.27% (7/43) of the patients had positive results in both their blood and aqueous humor samples. Conclusion: qPCR was able to detect T. gondii DNA in patients with toxoplasmic active focal necrotizing retinochoroiditis in the blood as well as the aqueous humor and can help with the diagnosis of the disease.

RESUMO Objetivo: Analisar o uso do PCR em tempo real (qPCR) na detecção do DNA do T. gondii no sangue periférico e no humor aquoso de pacientes com lesões de retinocoroidite focal, ativa por toxoplasmose. Métodos: Cinquenta e cinco pacientes com uveite infecciosa foram incluídos neste estudo. Os pacientes foram atendidos entre 2009 a 2013, no Departamento de Oftalmologia e Ciências Visuais da Universidade Federal de São Paulo. Quarenta e três pacientes tiveram o diagnóstico de lesões de retinocoroidite focal, ativa por toxoplasmose e, os outros 12 tiveram o diagnóstico de uveíte infecciosa não toxoplásmica e, por isso foram usados como grupo controle. A técnica de qPCR foi utilizada na detecção de DNA do T. gondii em amostras de sangue periférico e humor aquoso. Resultados: O qPCR foi positivo para o DNA do T. gondii em 37,21% (16/43) das amostras de humor aquoso, 2,33% (1/43) nas amostras de sangue periférico e, 16,27% (7/43) em ambas amostras simultaneamente. Conclusão: O qPCR foi capaz de detectar o DNA do T. gondii em pacientes com lesões de retinocoroidite focal, ativa por Toxoplasmose, no sangue bem como, no humor aquoso, podendo ajudar no diagnostico.

Increased serum levels of soluble tumor necrosis factor receptor-2 (sTNFR2) in patients with active toxoplasmic retinochoroiditis

This study aimed to investigate the serum levels of the cytokine TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in patients with toxoplasmosis retinochoroidits (TR) and controls. 37 patients with TR and 30 subjects with positive serology for toxoplasmosis but without history and signs of uveitis were included in this study. Serum concentrations of TNF-α, sTNFR1, and sTNFR2 were determined by ELISA. Serum concentrations of TNF-α and sTNFR1 were similar in controls (mean ± SD median values; 56.57 ± 141.96 and 504.37 ± 163.87, respectively) and TR patients (mean ± SD values, 121.62 ± 217.56 and 511.15 ± 189.30, respectively). Serum concentrations of sTNFR2 were higher in the uveitis group when compared to the control group (respectively, mean ± SD values, 1734.84 ± 379.32 and 1442.75 ± 309.47; p=0.002). There was no association between the serum levels of the molecules and the time of first symptoms, severity of vitreous haze, size or localization of active lesions, levels of visual acuity, and presence of vasculitis. These results suggest that TR is associated with changes in the circulating levels of inflammatory biomarkers, but they are not correlated with local/ocular signs.

Increased serum levels of soluble tumor necrosis factor receptor-2 (sTNFR2) in patients with active toxoplasmic retinochoroiditis.

This study aimed to investigate the serum levels of the cytokine TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in patients with toxoplasmosis retinochoroiditis (TR) and controls. 37 patients with TR and 30 subjects with positive serology for toxoplasmosis but without history and signs of uveitis were included in this study. Serum concentrations of TNF-α, sTNFR1, and sTNFR2 were determined by ELISA. Serum concentrations of TNF-α and sTNFR1 were similar in controls (mean ± SD median values; 56.57±141.96 and 504.37±163.87, respectively) and TR patients (mean ± SD values, 121.62±217.56 and 511.15±189.30, respectively). Serum concentrations of sTNFR2 were higher in the uveitis group when compared to the control group (respectively, mean ± SD values, 1734.84±379.32 and 1442.75±309.47; p=0.002). There was no association between the serum levels of the molecules and the time of first symptoms, severity of vitreous haze, size or localization of active lesions, levels of visual acuity, and presence of vasculitis. These results suggest that TR is associated with changes in the circulating levels of inflammatory biomarkers, but they are not correlated with local/ocular signs.

Susceptibility to toxoplasmic retinochoroiditis is associated with HLA alleles reported to be implicated with rapid progression to AIDS.

BACKGROUND/AIMS: The frequency of HLA markers associated with rapid progression to AIDS was evaluated in Brazilian patients with AIDS exhibiting or not toxoplasmic retinochoroiditis (TRC). METHODS: 98 AIDS patients (25 with TRC, 43 with anti-T. gondii antibodies but without TCR, and 30 without anti-T. gondii antibodies and without TCR) were studied. RESULTS: The HLA-B35 was significantly increased in TRC group (p=0.0038). CONCLUSION: The presence of HLA-B35 may simultaneously predispose to progression to AIDS and TRC.

Increased serum levels of CXCL8 chemokine in acute toxoplasmic retinochoroiditis.

PURPOSE: Chemokines have been implicated in the control of leucocyte infiltration in uveitis and in modulating angiogenesis in several ocular conditions. Toxoplasmic retinochoroiditis is a common cause of posterior uveitis. This study aimed to evaluate the serum concentrations of CC and CXC chemokines in patients with acute toxoplasmic retinochoroiditis. METHODS: The levels of five chemokines (CCL2, CCL11, CXCL9, CXCL8 and CXCL10) were evaluated in the serum of patients with active toxoplasmic retinochoroiditis (n = 55) and control subjects (n = 40). In a subset of patients (n = 18), a second measure of serum levels of chemokines was performed after the completion of oral treatment with pyrimethamine (25 mg/day), sulphadiazine (1 g, four times per day), folinic acid (7.5 mg/day) and prednisone (initial dose: 1 mg/kg/day) for approximately 30 days. RESULTS: Patients with toxoplasmic retinochoroiditis, notably those presenting with vasculitis, had increased serum levels of CXCL8 (mean +/- standard error of the mean [SEM] 35.1 +/- 6.5 pg/ml) compared with control subjects (mean +/- SEM 16.0 +/- 2.3 pg/ml; p = 0.01). There were no differences between patients and controls in serum levels of the other chemokines measured. The size of ocular lesions correlated significantly with serum levels of CXCL8 and CXCL9. After treatment, there was a significant reduction in serum levels of CXCL8. Severity of vitreous opacities did not correlate with serum levels of these chemokines. CONCLUSIONS: These data suggest a role for CXCL8 in the inflammatory process of acute toxoplasmic retinochoroiditis. Furthermore, CXCL8 may be a useful marker for patient follow-up.