DIAGNOSTIC AND PROGNOSTIC VALUE OF DETERMINATION OF INTERFERON-GAMMA IN CEREBROSPINAL FLUID IN HIV-ASSOCIATED NEUROLOGICAL DISEASES

Abstract

Neurological diseases develop in majority of patients with HIV, lead to high mortality, the predominant part of which is due to opportunistic infections of the central nervous system (CNS ). Interferon-gamma (IFN-γ) is one of the major cytokines that are important for the development of HIV neuropathogenesis.

The aim of the study – to investigate changes in the content of IFN-γ in blood and cerebral spinal fluid (CSF) and to investigate its association with the immunological status and viral load of HIV RNA in HIV-associated neurological diseases.

Materials and Methods. 48 patients with HIV infection and central nervous system disorders due to opportunistic infections, aged 21 to 54 years old, were examined. In the structure of disorders of the central nervous system, cerebral tuberculosis prevailed – 15 (31.3 %) patients and viral encephalitis (EBV , CMV , HSV ) – 11 (22.9 %) patients. The comparison group consisted of 7 healthy donors of the corresponding age. The content of IFN-γ in the blood and in the CSF was determined by the EL ISA method. Statistica v.6.1® and MedCalс v.11.5.0 (free download) were used for statistical analysis of the results of the study.

Results and discussion. Significant differences were found between the content of IFN-γ in CSF, depending on the outcome of the disease – the median of the indicator in lethal cases was three times higher than that in surviving patients – 9.0 (6.0–12.0) pg/ml versus 3.0 (1.0–7.0) pg/ml (p = 0.001 for the U-criterion), that is, the high level of IFN-γ in the cerebrospinal fluid directly correlated with the severity of the patient's condition and unfavorable prognosis (rs = 0.48; p <0.001). Direct correlations were found between the content of IFN-γ in CSF and the viral load of HIV RNA , both in CSF (rs = 0.44; p <0.01) and in blood (rs = 0.46; p <0.01) of patients with HIV-associated neurological diseases. An increase in the concentration of IFN-γ in serum was also associated with a high level of RNA copies (rs = 0.32; p <0.05) and a decrease in the number of CD4 cells (rs = -0.29; p <0.05). According to the results of the RO C analysis, it is determined that the high risk of an unfavorable course of HIV-associated CNS infection is predicted at an IFN-γ concentration in the cerebrospinal fluid of more than 4.0 pg / ml; the area under the RO C curve is AU C = 0.780 ± 0.067 (p <0.001) (sensitivity of the test 89.5 %, specificity – 65.5 %, accuracy – 75.0 %). The high probability of developing cerebral tuberculosis is predicted by increasing the concentration of IFN-γ in the CSF to 9.5 pg/ml and above – the area under the RO C curve AU C = 0.787±0.080 (p = 0.002) (sensitivity of the test 66.7 %, specificity – 90.9 %, diagnostic accuracy – 83.3 %) and the concentration of interferon gamma in the blood of more than 15 pg/ml (AU C = 0.690 ± 0.090 (p = 0.037) (sensitivity of the test 53.3 %, specificity – 84.8 % diagnostic accuracy – 75.0 %).

Conclusions. The high content of interferon-gamma in the cerebrospinal fluid is an important criterion for diagnosis of tuberculous lesion of the central nervous system. The increased level of IFN-γ in the cerebrospinal fluid accompanied by lethal outcome may be a predictor of the unfavourable progression of neurological disorders in HIV patients. Taking into account the obtained data of correlation and dispersion analysis, it can be assumed that the definition of IFN-γ in a complex with immunological parameters and viral load of HIV RNA in blood and CSF will increase its diagnostic and predictive value.