Immunodiagnostics of cerebral toxoplasmosis depending on permeability of blood-brain barrier

Abstract

The aim of the work was to detect a diagnostic value of CNSToxoIndex – index of correlation between albumin concentration and anti-toxoplasma antibodies, which reflects local production of anti-toxoplasma IgG in CNS compared with their level in blood. Materials and methods: 30 HIV-infected persons with the IV clinical stage (16 man and 14 women) aged from 25 to 49 years with clinical and instrumental signs of cerebral toxoplasmosis were selected from the general array of the patients treated in the Regional Clinical Infectious Hospital. A retrospective parallel detection of IgG T. gondii was performed in serum and CSF in patients, whose results of ELISA or PCR on T. gondii were positive. Blood serum and CSF were obtained from patients at the same time. All samples for analysis were stored at −20 °C and then tested on the RT-2100C Rayto Life and Analytical Sciences Co., Ltd (China) immunoassay analyser for quantitative detection of the level of specific anti-Toxicoplasma IgG. Detection of albumin concentration in serum and CSF was performed on the Chemray-120 Automated Biochemical Analyzer Rayto Life and Analytical Sciences Co., Ltd (China) using the Liquick Cor-ALBUMIN Diagnostic Kit. Results: Specific IgG to T. gondii in blood plasma was found in 27 patients (90%) while in CSF only in 7 (23 %). The results of the research in this group of patients were represented by the following parameters: patient 1 (blood antiToxo IgG – 200 IU/ml, blood albumin – 36 g/l, CSF antiToxo IgG – 10 IU/ml, CSF albumin – 0.8 g/l, CNSToxolndex – 2.3); patient 2 (150 / 40 / 90 / 0.7 / 34.3, respectively); patient 3 (90 / 35 / 64 / 0.25 / 99.6); patient 4 (140 / 39/ 10/ 0.19/ 14.7); patient 5 (88 / 52 / 48 / 0.21 / 135.1); patient 6 (160 / 48 / 50 / 0.15 / 100.0); patient 7 (122 / 42 / 15 / 0.17 / 30.4). Consequently, taking into consideration the diagnostic marker CNSToxolndex more than 10.0, cerebral toxoplasmosis was diagnosed only in six patients from seven, in whom anti-toxoplasma antibodies in CSF were detected. Patient 1, despite clinical symptoms similar to cerebral toxoplasmosis, and substitute signs of cerebral toxoplasmosis detected with the help of neuroimaging methods (volumetric formation of the right frontal lobe with a ring-shaped enhancement), availability of specific anti-toxoplasma antibodies in blood serum and CSF, diagnosis of cerebral toxoplasmosis has not been confirmed. M. tuberculosis DNA was found in CSF by PCR. Conclusions: CNSToxoIndex allows evaluating the local production of anti-toxoplasmic IgG in CNS and their diffusion from blood as a result of the blood-brain barrier damage and it is a powerful method of cerebral toxoplasmosis diagnostics in HIV-positive people as well.

Neuroimmunopathology in Toxoplasmic Encephalitis

“…Finally, it is worth mentioning that CNSToxoIndex evaluates the local synthesis of anti-toxoplasmic IgG in the CNS and their diffusion from blood as a consequence of blood-brain barrier disruption, and it is also a potent approach of TE diagnostics in HIV-positive individuals [99].…”

Cerebral toxoplasmosis in HIV-infected patients: a review

“…Positivity of CSF T. gondii PCR is related to the intracellular location of T. gondii , the number of lesions, and their distance from the CSF paths; therefore, a negative CSF T. gondii PCR does not exclude the diagnosis of cerebral toxoplasmosis. Specificity of CSF PCR is 96–100%, but sensitivity is below 50% [ 40 ]. Antiparasitic treatment reduces sensitivity of the PCR test, but primary prophylaxis does not.…”

“…Seronegativity may result from several conditions, including primary infection, reactivation of latent disease in individuals who cannot produce detectable antibodies, or testing with insensitive assays [ 37 ]. A comparison between CSF/blood anti-toxoplasma and blood/CSF albumin was proposed to improve the accuracy of cerebral toxoplasmosis diagnosis [ 40 ].…”