Leukocyte Elastase Activity Research Articles

Comparative Characteristics of Inflammatory Markers in Alzheimer’s Disease in Males and Females

Background: the role of the sex factor in the differences between the manifestations of normality and pathology is not limited to the phenomenon of sexual dimorphism. It is known that the prevalence of certain diseases in males and females is different, in particular, there is a multiple increase in the incidence of dementia in females compared to males in Alzheimer’s disease (AD). Taking into account the role of neuroinflammation in the pathogenesis of neurodegenerative diseases, there is reason to assume gender differences in inflammation indicators at different stages of dementia in AD. The aim of the study was to conduct comparative analysis of indicators of the inflammatory system in the blood plasma of males and females at different stages of Alzheimer’s disease. Patients, control group and methods: a total of 210 patients with AD (101 males and 109 females) aged 49 to 94 years (average age 72.3 ± 8.2) with varying degrees of dementia severity, i.e. mild, moderate, severe, were examined. In peripheral blood plasma, the enzymatic activity of leukocyte elastase (LE) and the functional activity of α1-proteinase inhibitor (α1-PI) were determined by the spectrophotometric method, and the level of C-reactive protein (CRP) and IL-6 were determined by the enzyme-linked immunosorbent method (ELISA). The control group consisted of 52 healthy people, who did not differ from the patients in age and gender. Results and discussion: in the blood of patients with varying severity of dementia in AD, a statistically significant increase in α1-PI activity was observed compared to controls (p < 0.0001), regardless of gender. For all subgroups of patients with AD, the indicators of LE enzymatic activity were within the control range or beyond its lower limit. Low LE activity was observed in males compared to females both in the general group and in moderate dementia (p = 0.005105, p = 0.028672, respectively). In severe dementia, a significant decrease in LE activity compared to the controls did not depend on gender. Low LE activity in the blood of patients with AD, along with elevated levels of other inflammatory markers, may reflect a critical violation of the permeability of the blood-brain barrier and/or functional exhaustion of neutrophils due to a long-term inflammatory process. In males, compared with females, an increase in the level of the pro-inflammatory cytokine IL-6 was detected in the general group and in moderate dementia (p = 0.021238, p = 0.027894, respectively). A highly significant increase in CRP levels was only detected in males in subgroups with different severity of dementia. CRP levels in males were significantly higher than in females at the stage of moderate and severe dementia (p = 0.000906, p = 0.000049, respectively). Conclusion: distinctive features of inflammatory markers spectrum were identified, depending on gender and severity of dementia in AD. These results can be used to develop sex-specific preventive or therapeutic strategies for patients with mild cognitive impairment to determine risk and resistance to developing dementia.

Effect of Trehalose Disaccharide on Activation of Microglia and Indices of Systemic Inflammation in an Experimental Model of Alzheimer's Disease.

In an experimental model of Alzheimer's disease in mice, oral administration of trehalose disaccharide reduces neuroinflammation assessed by the expression level of microglia activation marker Iba1 and affects the neutrophil degranulation activity. A potential anti-inflammatory effect of 4% trehalose solution associated with a decrease in the activity of leukocyte elastase in plasma was revealed.

Connection of molecular and cellular components of the immune system in endogenous psychoses with depressive-delusional symptoms

IntroductionThe data of current research indicate the participation of systemic inflammation in the pathogenesis of endogenous psychoses. Changes in the level of peripheral immune markers are associated with the development of neuroinflammation and correlate with the severity of psychopathological symptoms detected in patients. However, the association between individual components of the immune system involved in the development of endogenous psychosis remains poorly understood.ObjectivesTo study the connection between molecular and cellular components of the immune system in women with endogenous psychoses with depressive-delusional symptoms.Methods32 female patients aged 23 [17; 36] years with endogenous psychoses within different nosologies (F20, F21, F31, depressive-delusional conditions) and 17 women without clinical signs of psychiatric pathology were examined. The activity of leukocyte elastase (LE), α1-proteinase inhibitor (α1-PI), the proportion of four subpopulations of monocytes (classical CD14++CD16-, intermediate CD14++CD16+, nonclassical CD14+CD16+ and transitional CD14+CD16-) in plasma, activity of cytochrome-c oxidase (COX), glutamate dehydrogenase (GDH), glutathione s-transferase (GST) and glutathione reductase (GR) in platelets and functional activity of complement system (faCS) in serum were determined. The PANSS scale was used to assess the severity of psychopathological symptoms.ResultsIncreased activity of the inflammatory markers LE (p=0.033) and α1-PI (p=0.02) was found in the plasma of the patients. Increased percentage of pro-inflammatory monocytes (intermediate and transient) in plasma (p=0.003) was confirmed by negative correlations between CD14++CD16- and CD14++CD16+ (R=-0.685, p=0.00002), CD14++CD16- and CD14+CD16- (R=-0.608, p=0.0002), CD14++CD16- and CD14+CD16+ (R=-0.424, p=0.002). A decrease in GDH activity (p=0.0079), GST activity (p=0.002) and GR activity (p=0.0006) was observed in patient platelets, which can reflect changes in the activity of intracellular metabolic pathways. A positive correlation was found between COX activity and α1-PI (R=0.51, p=0.025). A significant decrease in faCS compared to control (p=0.0003) and a negative correlation between faCS and GST activity (R=-0.496, p=0.011) were observed. faCS was positively correlated with the degree of reduction in the PANSS score (R=0.416, p=0.038).ConclusionsThe revealed connection between molecular and cellular components of the immune system in patients with endogenous psychoses reflect activation of the systemic inflammatory response accompanied by changes in the ratio of monocyte subpopulations and impaired regulation of the complement system. The data obtained can be used to develop methods of monitoring patients taking into account their immunological features.Disclosure of InterestNone Declared

Logistic regression model for the prediction of asthenia development in schizophrenia based on inflammatory blood markers

IntroductionAccording to a number of authors, inflammation is involved in the development of asthenic syndrome in different diseases. The results of our own studies indicate that the main feature of the spectrum of inflammatory markers in patients with asthenic syndrome in schizophrenia is low enzymatic activity of leukocyte elastase against the background of high levels of other inflammatory markers. Presumably, the decrease in LE activity may be associated with functional exhaustion of neutrophils and/or their transmigration to the brain through the disrupted blood-brain barrier due to a long-term chronic inflammatory process.ObjectivesTo create a logistic regression model for predicting the development of asthenia in schizophrenia based on the analysis of the association between leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activity in blood plasma.MethodsA database including clinical and demographic parameters (ICD-10 diagnosis, duration of the disease, psychometric evaluation according to the PANSS and MFI-20 scales, sex and age) and immunological parameters (enzymatic activity of LE and functional activity of α1-PI in blood plasma) of 95 patients from 22 to 55 years old with paroxysmal-progressive (F20.x1) and paranoid (F20.00) schizophrenia was used to construct the model. An asthenic symptom complex was diagnosed in 61 patients.ResultsA binary logistic regression model linking the probability of developing asthenia to LE and α1-PI activity was constructed by analyzing a database of patients with schizophrenia.P=1/(1+exp [-(11.71-0.057-LE+0.027-α1-PI)] (2), whereP is the probability of asthenia development; exp is the base of the natural logarithm; 11.71 is the regression constant; 0.057 is the coefficient for LE; 0.027 is the coefficient for α1-PI.This model adequately describes the clinical data and has good predictive ability (sensitivity - 93.44%, specificity - 76.47%, AUC - 0.89).ConclusionsA binary logistic regression model was created to predict the development of asthenia in schizophrenia using immunological parameters LE and α1-PI. The model is highly effective and can complement clinical examination of patients with schizophrenia, contributing to the objective diagnosis of asthenic syndrome and, consequently, timely therapeutic correction.Disclosure of InterestNone Declared

Features of the spectrum of immune markers in patients with juvenile depression with clinically high risk of psychosis

IntroductionIdentification of biomarkers associated with the risk of psychosis manifestation in juvenile patients with depression may contribute to a better understanding of the pathogenesis of mental disorders and early diagnosis.ObjectivesTo determine the level of pro-inflammatory and anti-inflammatory cytokines and other inflammatory indicators in the plasma of juvenile patients with depression and clinically high risk of psychosis, and to study the correlation of these markers with the severity of psychopathologic symptoms.Methods80 young men aged 16-24 years with the first depressive episode (F32.1-2, F32.38, F32.8) were examined. Based on the severity of attenuated psychotic symptoms (APS) in the structure of depression according to the SOPS scale, all patients were divided into two groups - with clinically high risk of psychosis (n=58) and with depression without APS (n=22). The HDRS-21 and SANS scales were also used for psychometric assessment. Serum level of cytokines TNF-α, IL-6, IL-8, IL-10, TNF-α/IL-6 ratio, TNF-α/IL-10 ratio, leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activity, C-reactive protein (CRP) concentration, and the level of autoantibodies to S-100B protein were determined.ResultsBoth groups of patients showed a high level of inflammation assessed by LE and α1-PI activity (p>0.05). Significantly higher level of IL-6 (p=0.03), CRP concentration (p=0.026) and TNF-α/IL-10 ratio (p=0.032) were found in patients with clinically high risk of psychosis. This group was also characterised by high level of autoantibodies to the S-100B protein compared to patients with depression without APS (p=0.048). In the high clinical risk group, correlations were found between the SOPS positive subscale score and the level of TNF-α (R=0.32, p=0.017), IL-8 (R=-0.3, p=0.034), TNF-α/IL-6 ratio (R=0.30, p=0.021) and TNF-α/IL-10 ratio (R=0.32, p=0.014). The SOPS negative subscale score correlated with CRP concentration (R=0.3, p=0.043). The SOPS total score correlated with TNF-α/IL-10 ratio (R=0.31, p=0.021). In this group of patients, the level of IL-10 was found to correlate with the duration of the disease (R=0.48, p<0.001). In patients with depression without APS, the level of IL-6 was correlated with the severity of depression according to the HDRS scale, and the level of TNF-α was associated with the duration of the depressive episode (R=0.51, p=0.029).ConclusionsThe obtained results confirm the involvement of inflammation in the development of juvenile depression. Qualitative and quantitative characteristics of the spectrum of immune markers and the cytokine profile, and correlations with the severity of psychopathologic symptoms were revealed in patients with clinically high risk of psychosis.Disclosure of InterestNone Declared

Immunological predictors of rhythmic transcranial magnetic stimulation (rTMS) efficiency in patients with treatment-resistant schizophrenia

IntroductionModel and clinical studies demonstrate the efficiency of rhythmic transcranial magnetic stimulation (rTMS) in diseases associated with neuroinflammation. The therapeutic potential of rTMS is related to modulation of neuroplasticity in the CNS, activation of neurogenesis and reduction of neuroinflammatory processes. Presumably, one of the factors that determines the efficiency of rTMS can be the features of the immune status of patients.ObjectivesTo reveal the features of the spectrum of inflammatory markers in patients with treatment-resistant schizophrenia with different efficiency of rTMS.Methods 31 male patients aged 16 to 47 years (mean age 29.9 ± 8.4 years) with treatment-resistant schizophrenia who developed a first psychotic episode in adolescence (19-25 years) were examined. The course of rTMS was conducted for 3 weeks (15 sessions). Depending on the dynamics of clinical and psychometric parameters after the course of rTMS, the patients were divided into three groups: group 1 - with worsening of clinical condition (n=8); group 2 - without therapeutic effect (n=12); group 3 - with good therapeutic response (n=11). Before rTMS, leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activity, and the levels of autoantibodies to S-100B protein and myelin basic protein (MBP) in the plasma of patients were determined. The parameters of 18 healthy male donors without clinical signs of psychiatric and somatic pathology were used as controls.ResultsAll groups of patients were characterised by moderate and high levels of immune system activation, determined by a complex of inflammatory and autoimmune markers. At the same time, the high level of immune system activation in patients with low MTR efficiency was associated with low LE activity in plasma (within the reference range or below the lower limit - 200.6 (168.5- 220.3) nmol/min·mL), which was not consistent with the overall level of inflammation. This group of patients also showed high levels of antibodies to MBP compared to control values (p<0.05). The low LE activity can be explained by the transmigration of neutrophils from the blood to the brain due to a critical increase in the permeability of the blood-brain barrier, which is largely controlled by LE.ConclusionsThe study confirmed the participation of immune mechanisms in the formation of therapeutic resistance in schizophrenia and revealed the characteristics of the spectrum of immune markers in patients with low efficiency of rTMS.Disclosure of InterestNone Declared

Effect of Neurotropic and Immunotropic Drugs on Leukocyte Elastase Activity In Vitro.

Leukocyte elastase is a marker of inflammation. Previously, a relationship was found between the severity of mental disorders in patients and elastase-like activity of blood plasma. The effect of various neurotropic drugs on leukocyte elastase activity was analyzed in an in vitro experiment. We revealed an inhibitory effect of the benzodiazepine tranquilizers diazepam and bromodihydrochlorophenylbenzodiazepine and immunomodulators aminodihydrophthalazinedione and diclofenac on the plasma elastase-like activity of healthy donors and pure human neutrophil elastase. The antipsychotics chlorpromazine and alimemazine, as well as the nootropic vinpocetine increased elastase-like activity in a dose-dependent manner. The activating effect of chlorpromazine and vinpocetine, but not alimemazine, was reproduced in neutrophil elastase. We hypothesized that these drugs can affect the development of inflammatory reactions in the complex therapy of mental disorders.

Diagnostics and Assessment of the Severity of Alzheimer’s Disease: Machine Learning Algorithms Based on Markers of Inflammation

Background: as the most common form of dementia, Alzheimer’s disease (AD) is characterized by cognitive deterioration and usually begins with loss of memory of recent events. It is important to search for biological, sensitive and affordable methods that could be used for early diagnostics of AD and determine the severity of the disease.Objective: to develop machine learning algorithms based on such inflammatory markers as the enzymatic activity of leukocyte elastase (LE) and the functional activity of the α1-proteinase inhibitor (α1-PI) for diagnosing and assessing the severity of AD.Patients and methods: the study included128 people aged 55 to 94 years (73.7 ± 7.9 years), of which 91 patients were diagnosed with Alzheimer’s disease and 37 apparently healthy people (control). The indicators of LE and α1-PI in blood plasma were used as classifying features for building models. The following algorithms were used to build a machine learning model: Optimal Valid Partition (OVP), logistic regression (LR), support vector machine (SVM), random forest (RF), gradient boosting (GB) and statistically weighted syndromes (WSWS). The predictive performance of the constructed classiers was evaluated by the overall accuracy (accuracy), sensitivity (sensitivity), specificity (specificity), F-measure and ROC-analysis.Results: the developed machine learning algorithms made it possible to reliably divide the general group of subjects (patients + conditionally healthy), as well as patients with different AD severity, into 4 quadrants of a two-dimensional diagram in the LE and α1-PI coordinates and showed close and fairly high predictive efficiency.Conclusion: the developed machine learning algorithms have proven close and sufficiently high prognostic efficacy for assessing the severity of AD based on inflammatory markers (enzymatic activity of LE and functional activity of α1-PI) and, probably, can be useful for early diagnostics of the disease and timely administration of therapy.

Clinical and psychopathological characteristics of patients with late-onset schizophrenia and schizophrenia-like psychoses in clusters identified by biological parameters

To assess clinical and psychopathological characteristics of late-aged female patients with late-onset psychoses in clusters formed on the basis of biochemical and immunological blood parameters. We examined 59 women with schizophrenia and schizophrenia-like psychoses with onset after 40 years (ICD-10 F20, F22.8, F25, F23, F06.2), including 34 women with late-onset (40-60 years) and 25 with very late onset psychoses (after 60 years). At the time of hospitalization, a clinical/ psychopathological study was carried out using CGI-S, PANSS, CDSS, and HAMD-17, as well as the activities of glutathione reductase (GR) and glutathione-S-transferase (GT) have been determined in erythrocyte hemolysates, and the activities of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) have been assessed in blood plasma. Biochemical and immunological parameters have been also determined in 34 age-matched mentally healthy women. Clustering by signs such as GR, GT, LE and α1-PI has yielded two clusters of objects (patients) significantly different in GT (p<0.0001), LE (p<0.0001), and α1-PI (p<0.001) activities. Relatively to the controls, in the cluster 1 patients, the activities of GST and α1-PI are increased, the activity of LE is decreased, whereas, in the cluster 2 patients, the activity of GR is decreased, and the activities of LE and α1-PI are increased. Cluster 1 patients differ from cluster 2 patients in greater severity of the condition (CGI-S, p=0.04) and higher total scores on PANSS subscales' items. Cluster 1 includes 76% of patients with very late onset. Different correlations between clinical and biological signs are found in two clusters. The identified clusters have different clinical and psychopathological characteristics. Dividing patients into subgroups according to biochemical and immunological parameters is promising for the search for differentiated therapeutic approaches.

HLDF-6-H Peptide Exhibits an Anti-inflammatory Effect in the Development of Depression in an MPTP Model of Parkinson's Disease

In this work, we investigate the anti-inflammatory effect of the HLDF-6-H peptide (Thr-Gly-Glu-HseHis-Arg) in a model of the presymptomatic stage of Parkinson’s disease (PD). This peptide is a bioactive fragment of the HLDF leukocyte differentiation factor. The presymptomatic stage of PD was modelled by introducing moderate doses of MPTP toxin to C57Bl/6 mice. HLDF-6-H was administered intranasally at a dose of 300 μg/kg daily for three weeks. The severity of depression was determined by the time of immobilization in a Porsolt test. The serum levels of 10 steroids were determined using MS analysis. The activity of inflammatory markers leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) was determined using kinetic methods. The development of an inflammatory process under the influence of MPTP is evidenced by an increase in the activity of α1-PI; the anti-inflammatory effect of the peptide is manifested in a decreased activity of LE and α1-PI. At the same time, the immobilization time of mice in a Porsolt test positively correlated with α1-PI and LE, which may indicate the role of inflammation in the development of depression. A positive correlation between estradiol and LE was found in the general sample of mice. In the group of mice treated with the peptide, α1-PI correlated positively with corticosterone and negatively with estradiol and androstenedione. It can be assumed that the anti-inflammatory effect of the peptide is associated with the regulation of corticosteroids and sex hormones. Hence, the applied experimental model confirmed the development of a depressive-like syndrome and neuroendocrine disorders in the presymptomatic stage of PD. The long-term use of HLDF-6-H has antidepressant and anti-inflammatory effects.

Correlations between different protein species of oral rinse MMP-8 and patient-related factors.

The aim of this study is to examine correlations between different oral rinse matrix metalloproteinase (MMP)-8 protein species in western blot (WB) analysis, quantitative MMP-8 measurements, and patient-related factors. Elevated activated MMP-8 (aMMP-8) associate with periodontitis and a diagnostic point-of-care technology has been developed based on aMMP-8. In WB, different MMP-8 protein species can be analyzed. Relative abundancyof fragmented 20-25 kDa forms in WB has been associated with and reflects MMP-8 activation and related fragmentation and elevated quantitative aMMP-8 measurements. A random sample of 192 participants from a periodontal disease screening study was used for this study. Oral rinse samples for biomarker analyses were collected before clinical periodontal examinations. aMMP-8 immunofluorometric (IFMA) and WB analysis (utilizing the same monoclonal antibody, 8708), polymorphonuclear leukocyte (PMN) elastase activity test and tissue inhibitor of metalloproteinases (TIMP)-1 ELISA levels were performed from the oral rinse samples. Distinct MMP-8 protein species were differentiated in the WB analysis. Principal component (PC) analysis was conducted to explore correlation patterns between the different species. Adjusted correlation analysis between the extracted PCs of WB and aMMP-8 IFMA levels and multilevel regression analysis were conducted to explore if the other periodontal disease-related biomarkers and clinical surrogate measures and patient-related factors are co-variating with the extracted components. Distinct correlation patterns between the MMP-8 protein species were observed. The first four PCs explained 89% of the whole variance in PC analysis. Statistically significant correlation (p < 0.05) were observed as follows: PC1 positively with 21 kDa (r = .69) and 25 kDa fragments (r = .55) and negatively with 150 kDa complexes (r = -.46). PC2 correlated with 45 (r = .70) and 55 kDa (r = .65) activated forms, PC3 with 70-80 kDa latent proforms (r = .63) and 90-100 kDa complexes (r = .67), and PC4 with 35 kDa fragments (r = .81). There were significant correlations between quantitative (IFMA) aMMP-8 measurements and PC1 (p < 0.001), PC2 (<0.05) and PC3 (<0.05) but not with PC4. In multilevel regression models age, PMN elastase activity, TIMP-1 levels, and a number of 4-5 mm periodontal pockets were associated with PC1, nonsmoking with PC2, ageand PMN elastase activity with PC3, and age and smoking with PC4. Relative abundancy of fragmented 21-25 kDa protein species was correlated with the quantitative aMMP-8 (IFMA) measurements, which is in line with previous results. Different patient-related factors (smoking, age, proteolytic activity) may modify the formation of different MMP-8 protein species in oral rinse samples and may cause variability in quantitative aMMP-8 measurement.

Predicting the Dynamics of Mild Cognitive Impairment According to Immunological Parameters

Background: neuroin flammation is an important link in the pathogenesis of pre-dementia cognitive impairment and the development of dementia in Alzheimer’s disease.The aim of the study was to determine the prognostic value of inflaammatory markers (enzymatic activity of LE and its inhibitor alpha1-PI) at the stage of mild cognitive impairment for subsequent follow-up evaluation.Patients and methods: a total of 103 patients with an amnesic type of mild cognitive impairment (aMCI) aged 50 to 89 years (mean age 68.1 ± 9.4 years) were examined. Mental status of the patients was assessed clinically and by psychometric scales and tests. After 3 years of observation, the patients were divided into two groups depending on the dynamics of cognitive status: the 1st group consisted of 49 patients with progression of cognitive decline to the degree of dementia; the 2nd group included 54 patients with a stable state of cognitive functions. The control group included 61 subjects of the same age and gender. The enzymatic activity of leukocyte elastase (LE) and the functional activity of the α1-proteinase inhibitor (α1-PI) were determined in blood plasma. Cluster analysis was used to isolate immunotypes.Results: the functional activity of α1-PI at the starting point of the study in patients of both follow-up groups exceeded the control values (p = 0.000001, p = 0.000006, respectively). Follow-up groups differed in LE activity at the initial stage. In patients of the 1st group (with an increase in cognitive impairment) LE activity did not differ from the control values (p = 0.144651). Group 2 (with stable cognitive functions) was characterized by a significantly higher LE activity compared to the controls (p = 0.000000). Cluster analysis made it possible to identify two immunotypes that differed in LE activity. In the 1st cluster, LE activity was within the control range and below, it mainly included patients of the 1st follow-up group (68.3%). In the 2nd cluster LE activity exceeded the control values, this cluster mainly consisted of patients of the 2nd follow-up group (85.0%) (χ2 = 27.82, p = 0.0000).Conclusion: the revealed reliable differences in the distribution of follow-up groups for immunological clusters indicate the possibility of using indicators of LE and α1-PI activity for diagnosing and predicting the dynamics of mild cognitive decline.

Clinical and Immunological Aspects of Delusional Disorders in Paranoid Schizophrenia

Background: insufficient study of heterogeneous delusional disorders in schizophrenia and the role of inflammation in the development of the disease served as the basis for this study. The aim: to establish the role of immune mechanisms in the processes of the interaction of different forms of delusional symptom complexes in schizophrenia. Patients: 60 patients (mean age 38.4 ± 1.11 years) with the diagnosis “paranoid schizophrenia, continuous progressive course” (F20.00, ICD-10) were included in the study. The state of patients was defined by persistent delusional/hallucinatory delusional disorders. Based on the clinical assessment, patients were divided into three groups: 27 patients (group 1) with interpretative delusion, 22 patients (group 2) with delusion of influence based on the phenomena of mental automatism, and 11 examinees (group 3) with mixed forms of delusions (interpretative and delusions of influence with mental automatism). The control group consisted of 17 mentally and somatically healthy people, comparable with the patients by sex and age. Methods: inflammatory and autoimmune markers leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activity, leukocyte inhibitor index (LII) and antibody (aAb) level to S100B and MBP were determined in the blood. Results: in all groups of patients, an increase in the activity of LE and α1-PI was revealed compared with the control (p &lt; 0.05). In group 2, an increase in aAb level to S100B was also detected (p &lt; 0.05). Intra-group differences in LE activity served as the basis for dividing patients into three clusters. Cluster 1 was characterized by moderate activation of the immune system and was represented mainly by patients with interpretative delusions (54.5% of patients in the corresponding clinical group). Clusters 2 and 3 were distinguished by a higher level of immune system activation. A distinctive feature of cluster 3 was low LE activity against the background of high α1-PI activity and elevated level of aAb to S100B. Clusters 2 and 3 were represented mainly by patients with delusion of influence (74.1%). Сonclusion: the study confirmed the involvement of inflammation in the pathophysiology of delusional disorders in paranoid schizophrenia and allowed us to identify the relationship between the psychopathological structure of these disorders and the features of the spectrum of immune markers. The highest level of activation of the immune system, as well as immunological features presumably indicating impaired permeability of the blood-brain barrier, were associated mainly with delusions of influence with the phenomena of mental automatism.

Clinical and immunological characteristics of depressive patients with a clinical high risk of schizophrenia

Objective: To study clinical and immunological characteristics of depressive patients with high clinical risk of schizophrenia. Materials and methods: We examined 30 depressive patients with attenuated positive symptoms (APS), which indicates a clinically high risk of schizophrenia, 20 depressive patients without APS and 27 healthy volunteers with no mental disorders. APS identified according to the presence of three or more scores on at least one of the following items on the Scale of Prodromal Symptoms (SOPS) positive symptoms subscale: P1 (Unusual thought content/Delusional ideas), P2 (Suspiciousness/Persecutory ideas) and P4 (Perceptual abnormalities/Hallucinations). The psychometric assessment was carried out on the Hamilton Depression Rating Scale (HDRS), SOPS, and the Scale for Assessment of Negative Symptoms (SANS). The activity of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI), the autoantibodies to neoantigens S100B and myelin basic protein, and the ratio of LE and α1-PI activity or Leukocyte Inhibitory Index (LII) were determined. Results: The activity of inflammatory markers LE and α1-PI was increased in patients in both clinical groups compared with controls. In the total group of patients, the associations between LII and the score on the positive subscale SOPS, and between LII and the score on the negative subscale SOPS and SANS scale with the most pronounced association with the SANS subscales «Affective Flattening or Blunting» and «Alogia» were established. Conclusion: The identified correlations between immune response features and positive and negative symptoms in depressive patients may have prognostic value for establishing a high risk of schizophrenia.

Clinical-Immunological Correlates in Post-COVID-19 Endogenous Psychoses.

Objectives. To carry out a clinical and immunological study of the potential impact of coronavirus infection on the course of endogenous psychoses. Materials and methods. A total of 33 female patients aged 16-48 years with depressive-delusional states (F20.01, F21, F31) developing after coronavirus infections took part; group 1 consisted of 15 people who developed depressive-delusional states 1-2 months after COVID-19; group 2 consisted of 18 people with similar psychoses developing at later time points (2-6 months). The severity of psychopathological symptoms was assessed using the PANSS and HDRS-21 scales. The activity of inflammatory markers leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) was determined in patients' blood. Absolute neutrophil and lymphocyte contents and their ratio (the neutrophil:lymphocyte index) were also evaluated. Standard values for indicators from healthy donors corresponding to patients in terms of age and sex were used as control values. Results. Endogenous psychosis developing at longer intervals after coronavirus infection (group 2) was found to be associated with "typical" inflammatory reactions, with increases in the activity of acute-phase proteins (α1-PI: 43.0 (35.6-49.7) IU/ml, p = 0.001) and neutrophil degranulation activity (LE - 254.8 (238.0-271.0) nmol/min·ml, p < 0.001), which was associated with the development of depressive-delusional states with dominance of manifestations of positive affectivity (anxiety, melancholy) and the extended nature of delusional disorders, which were mostly incongruent to affect. Conversely, development of endogenous psychosis during the first two months after COVID-19 (group 1) was characterized by a spectrum of inflammatory biomarkers with a decrease in neutrophil count ((2.6 ± 0.9)·109/liter, p < 0.05) and low LE activity (196 (172-209.4) nmol/min·ml, p < 0.001). This immunological profile was associated with predominance of manifestations of negative affectivity (apathy, asthenia, adynamia) in the structure of depressive-delusional states and the relatively undeveloped nature of delusional disorders, which were predominantly congruent to affect. Conclusions. The clinical and biological correlates found here presumptively indicate that experience of COVID-19 infection has a modulatory effect on neuroinflammation and the structure of endogenous psychosis.

Clinical and Immunological Parameters in the Diagnostics of Asthenic Syndrome in Patients with Chronic Heart Failure

Background: the significance of the asthenic syndrome as one of the most distressing symptoms affecting the clinical outcome of chronic heart failure (CHF), and insufficient understanding of the pathophysiological aspects of asthenia determines the need to study the clinical and biological features of this syndrome in cardiac pathology. Objective: to determine of a number of inflammatory and autoimmune blood parameters in patients with CHF associated with asthenic disorders in comparison with hypertensive disease in relation to clinical and gender-age characteristics of patients. Patients and methods: 62 patients with CHF (study group; 64.4 ± 9.7 years) and 50 patients with hypertensive disease (HD) (comparison group; 55 ± 9.7 years) were examined. Somatic examination included consultation with a cardiologist. Psychometric assessment was performed using the MFI-20 scale and the MLHFQ questionnaire. In patients' blood, leukocyte elastase (LE) activity, α1-proteinase inhibitor (α1-PI), leukocyte inhibitory index (LII), concentration of CRP, IL-6, and levels of antibodies to S-100B and myelin basic protein were determined. Results: patients with CHF characterized by more pronounced manifestations of all dimensional asthenic disorders compared to patients with HD. The deterioration of CHF patients' quality of life was accompanied by the aggravation of asthenic symptoms on all subscales of the MFI-20 scale. In patients with CHF and HD, multidirectional changes in the leukocyte inhibitory index and significant quantitative differences in other immune parameters compared with the normative values were detected. CHF associated with asthenia was characterized by decreased activity of the blood proteolytic system (decrease in LII), a significant increase in the concentration of IL-6, CRP and antibodies to S-100B in the blood of patients compared to comparison group. Negative correlations between LE activity and several dimensions of the MFI-20 scale, and positive correlations between the severity of general asthenia, patient age, and IL-6 and CRP concentrations indicate the involvement of inflammation in the pathophysiology of asthenic disorders in the cardiac pathology discussed. Conclusion: low activity of blood proteolytic system and high level of inflammation are unfavorable factors in the development of asthenia in chronic heart failure. Qualitative and quantitative features of the spectrum of immunological parameters in patients with CHF are correlated with clinical and genderage characteristics and reflect the severity of both cardiological changes and asthenic symptoms.

Inflammatory markers in organic nonpsychotic disorders

To determine the indicators of systemic inflammation in peripheral blood samples of patients with organic non-psychotic disorders. The study included 60 patients, aged 56.9±7.7 years, with a disease duration of 7.3±5.55 years, with a verified ICD-10 diagnosis «Organic emotionally labile (asthenic) disorder» (F06.6) and «Organic Anxiety Disorder» (F06.4). Patients with organic asthenic disorder were divided into two groups according to the prevailing symptoms: 36 patients with asthenic-cephalgic syndrome (AC); 10 patients with astheno-dysthymic syndrome (AD); the third group (n=14) included patients with organic anxiety disorder (AND). The control group consisted of 65 people matched for age and sex with patients. The activity of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) was determined by the spectrophotometric method, the levels of aAB to S100b and MBP were determined by ELISA. The protease-inhibitory index (PII), i.e., the ratio of LE activity to α1-PI, was calculated. A significant increase in LE (235.4 [216.4; 258.1] nmol/min*ml, p<0.001), the functional activity of α1-PI (43.1 [38.7; 47.6] u/ml, p<0.001), the level of aAB to S100b (0.78 [0.70; 0.89] opt.units, p<0.05) and a decrease in PII (6.19 [5.32; 6.9], p<0.05) in the group of patients with organic non-mental disorders compared with controls were shown. Deviations from the normal values of immune markers of inflammation in blood samples were also found in various syndromes. Clustering of the total group of patients by LE activity made it possible to identify 2 immunotypes with a balanced and unbalanced inflammatory process, confirming the clinical diversity of the disease: 60% of patients with AC syndrome belong to the 1st cluster, in which the ratio of immune markers characterizes a balanced inflammatory process aimed at restoration of homeostasis; 80% of patients with organic AND belong to the second cluster, which characterizes low proteolytic activity and imbalance of inflammation, which is an unfavorable prognostic factor in terms of the further course of the disease and therapy. The results confirm the importance of the inflammatory link in the neuroprogression of organic non-psychotic disorders. The identified features of the immune response can serve as an additional paraclinical criterion for differential diagnosis and evaluation of the prognosis of the further development of the disease.

Features of inflammatory reactions in patients with juvenile depression with a clinically high risk of psychosis

To determine the levels of pro-inflammatory and anti-inflammatory cytokines and inflammatory markers such as C-reactive protein, leukocyte elastase, α1-proteinase inhibitor, autoantibodies to neuroantigens in the blood of patients with adolescent depression with clinical high risk for psychosis (CHR-P) and to study the relation of these biological markers to the features of psychopathological symptomatology of the patients. Eighty young adults, aged 16-24 years, with the first depressive episode (F32.1-2, F32.38, F32.8) were studied. Based on the presence of attenuated positive symptoms in the structure of depression, all patients were divided into two groups: with CHR-P (clinical group, n=58) and without CHR-P (comparative group, n=22). The HDRS-21, SOPS, and SANS were used for psychometric assessment of the patients. Serum levels of cytokines TNF-α, IL-6, IL-8, IL-10, and concentration of C-reactive protein (CRP) were determined. Leukocyte elastase (LE) activity, α1-proteinase inhibitor (α1-PI) activity, and plasma levels of autoantibodies to S100B protein and myelin basic protein (MBP) were assessed. Both groups of patients were characterized by the high levels of inflammation as assessed by LE (250.5 (226.2-280.8) nmol/min·ml vs 248.3 (226.8-284.5) nmol/min·ml) and α1-PI activity (44.4 (37.5-50.1) IE/ml vs 45.2 (36.4-49.9) IE/ml). Higher levels (p<0.05) of IL-6 (1.22 (0.64-2.2) pg/ml), CRP (0.93 (0.18-3.18) mg/l), and TNF-α/IL-10 (0.34 (0.2-0.47)) were detected in the group with CHR-P. This group was also characterized by higher levels of antibodies to the S100B protein 0.78 (0.69-0.84 units of opt.density) compared with the group without CRH-P (p<0.05). In each clinical group, different correlations between clinical, psychometric and biological parameters were revealed. The results confirm the involvement of inflammation in the development of depression in youth and indicate a different role of the inflammatory markers analyzed in the formation of CHR-P. The differences in the spectrum of inflammatory markers in depressed patients suggest a more pronounced pro-inflammatory potential in the group with CHR-P.

Markers of Systemic Inflammation in Assessing the Effectiveness of Neurocognitive Rehabilitation in Aged Patients with Mild Cognitive Impairment

Background: the results of previous studies suggest that the level of activation of inflammatory responses in the periphery correlates with the severity of cognitive impairment in patients with neurodegenerative diseases and can serve as an indicator of the activity of the current pathological process in the brain. Epigenetic factors are suggested to influence the regulation of (neuro)inflammation and cognitive recovery in elderly patients, which opens up a wide spectrum of therapeutic strategies for the treatment of age-associated diseases. Objective: to evaluate the possible effects of a comprehensive neurocognitive rehabilitation program on cognitive functioning and blood immunological parameters of elderly patients with mild cognitive impairment (MCI).Patients and methods: 507 participants of the “Memory Clinic” rehabilitation program with signs of MCI (F06.7, F06.78 according to ICD-10) were examined before the start of neurocognitive training and after its completion (after six weeks). Some patients (11.6%) were observed clinically one year after their inclusion in the program. Cognitive status was assessed using the Modified Hachinski Ischemic Scale, the Mini-Mental State Examination, the Montreal Cognitive Assessment, and the Clock Drawing Test. Enzymatic activity of leukocyte elastase (LE), functional activity of α1-proteinase inhibitor (α1-PI), and levels of antibodies to S-100B and myelin basic protein were determined in patients’ blood. The parameters of healthy donors were used as controls.Results: immunological examination of patients before the rehabilitation program revealed increased LE and α1-PI activity in the overall group compared to controls (p &lt; 0.001 and p &lt; 0.05). Using a previously developed regression model to identify a high-risk group for Alzheimer’s disease (AD) among patients with MCI, all subjects were divided into two groups (cut-off value p = 0.65). Group 1 (low-risk of AD, n = 330) was characterized by increased LE activity and α1-PI (p &lt; 0.001), Group 2 (highrisk of AD, n = 177) was distinguished by decreased LE activity (p &lt; 0.001) accompanied by high α1-PI activity (p &lt; 0.001). After neurocognitive training, differently directed variants of the dynamics of immunological parameters associated with the severity of patients’ cognitive impairment on psychometric scales were identified in each group. For the most of the examined patients (61.3%) the training program turned out to be effective, which was confirmed by the positive dynamics of the psychometric scores and relative normalization of the blood inflammatory markers (p &lt; 0.05). The highest effect of the rehabilitation program was typical for patients not included in the high-risk group for AD (p &lt; 0.001). Follow-up examination revealed stabilization of cognitive functioning in 93.2% of those examined, most of whom were patients with an initially low risk of developing the disease (p &lt; 0.01).Conclusion: neurocognitive rehabilitation of patients with MCI carried out in the “Memory Clinic” conditions can be considered as a social epigenetic factor modulating the current pathological process in patients with cognitive disorders, which is confirmed by objective immunological markers.

Dynamics of immune markers in different variants of post-psychotic depression after first-episode psychosis in young adult age

IntroductionResearch in recent decades focuses on understanding the role of the immune system in First-Episode Psychosis (FEP) at a young age. Our studies indicate that different stages of schizophrenia differ in the spectrum of inflammation markers. These indicators reflect the activity of the pathological process, using them as markers of the clinical state of patients at different stages of the disease.ObjectivesTo assess the relationship of immune markers with the clinical features of remission in patients after FEP.MethodsFifty patients aged 15-25 years with post-psychotic depression (PD) after FEP (F20, F25) and 30 healthy men were included in the study. The follow-up period was two years. PD typological variants with positive affectivity (PA) (n=30) and negative affectivity (NA) (n=20) were distinguished. Leukocyte elastase (LE), a1-proteinase inhibitor (a1-PI) activity, and S-100B autoantibodies in plasma samples were measured.ResultsThe increase of LE and a1-PI activity in plasma of both types of PD patients compared to controls was detected (p&lt;0.01). There was the highest LE activity and S-100B autoantibodies in PD with NA (p&lt;0.05). The different dynamics of immune markers in both groups were correlated to the clinical features of remission. PD with PA was associated with a decrease in inflammatory markers (p&lt;0.05) and a favorable prognosis. PD patients with NA had a further increase in LE activity and S-100B autoantibodies (p&lt;0.01), and an unfavorable prognosis.ConclusionsThe results confirm using the immune indicators as markers to assess the quality of remission after FEP in young adult age and the risk of recurrent psychotic attacks.DisclosureNo significant relationships.