Blood Growth Factor Levels in Patients with Systemic Lupus Erythematosus: High Neuregulin-1 Is Associated with Comorbid Cardiovascular Pathology.

Patients with systemic lupus erythematosus (SLE) are known to frequently suffer from comorbid cardiovascular diseases (CVDs). There are abundant data on cytokine levels and their role in the pathogenesis of SLE, while growth factors have received much less attention. The aim of this study was to analyze growth factor levels in SLE patients and their association with the presence of comorbid CVDs. The serum concentrations for the granulocyte-macrophage colony-stimulating factor (GM-CSF), nerve growth factor ß (NGFß), glial cell line-derived neurotrophic factor (GDNF), and neuregulin-1 ß (NRG-1ß) were determined in the SLE patients (n = 35) and healthy individuals (n = 38) by a Luminex multiplex assay. The NGFß and NRG-1ß concentrations were shown to be significantly higher in the total group of SLE patients (median [Q1-Q3]: 3.6 [1.3-4.5] and 52.5 [8.5-148], respectively) compared with the healthy individuals (2.9 [1.3-3.4] and 13.7 [4.4-42] ng/mL, respectively). The GM-CSF and GDNF levels did not differ. Interestingly, elevated NRG-1ß levels were associated with the presence of CVDs, as SLE patients with CVDs had significantly higher NRG-1ß levels (99 [22-242]) compared with the controls (13.7 [4.4-42]) and patients without CVDs (19 [9-80] ng/mL). The model for the binary classification of SLE patients with and without CVDs based on the NRG-1ß level had an average predictive ability (AUC = 0.67). Thus, altered levels of growth factors may be associated with comorbid CVDs in SLE patients.

Biochemical, Hematological, Inflammatory, and Gut Permeability Biomarkers in Patients with Alcohol Withdrawal Syndrome with and without Delirium Tremens.

Background: Delirium Tremens (DT) is known to be a serious complication of alcohol withdrawal syndrome (AWS). Neurotransmitter abnormalities, inflammation, and increased permeability are associated with the pathogenesis of AWS and DT. However, the biomarkers of these conditions are still poorly understood. Methods: In this work, biochemical, hematologic, inflammatory, and gut permeability biomarkers were investigated in the following three groups: healthy controls (n = 75), severe AWS patients with DT (n = 28), and mild/moderate AWS without DT (n = 97). Blood sampling was performed after resolution of the acute condition (on 5 ± 1 day after admission) to collect clinical information from patients and to investigate associations with clinical scales. Biomarker analysis was performed using automated analyzers and ELISA. Inflammatory biomarkers included the erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), and platelet-to-lymphocyte ratio (PLR). Results: Among the biochemical biomarkers, only glucose, total cholesterol, and alanine aminotransferase (ALT) changed significantly in the analyzed groups. A multiple regression analysis showed that age and ALT were independent predictors of the CIWA-Ar score. Hematologic biomarker analysis showed an increased white blood cell count, and the elevated size and greater size variability of red blood cells and platelets (MCV, RDWc, and PDWc) in two groups of patients. Gut permeability biomarkers (FABP2, LBP, and zonulin) did not change, but were associated with comorbid pathologies (alcohol liver disease and pancreatitis). The increase in inflammatory biomarkers (ESR and PLR) was more evident in AWS patients with DT. Cluster analysis confirmed the existence of a subgroup of patients with evidence of high inflammation, and such a subgroup was more frequent in DT patients. Conclusions: These findings contribute to the understanding of biomarker variability in AWS patients with and without DT and support the heterogeneity of patients by the level of inflammation.

Association of Peripheral Inflammatory Biomarkers and Growth Factors Levels with Sex, Therapy and Other Clinical Factors in Schizophrenia and Patient Stratification Based on These Data.

Multiple lines of evidence are known to confirm the pro-inflammatory state of some patients with schizophrenia and the involvement of inflammatory mechanisms in the pathogenesis of psychosis. The concentration of peripheral biomarkers is associated with the severity of inflammation and can be used for patient stratification. Here, we analyzed changes in serum concentrations of cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-21, APRIL, BAFF, PBEF/Visfatin, IFN-α, and TNF-α) and growth/neurotrophic factors (GM-CSF, NRG1-ß1, NGF-ß, and GDNF) in patients with schizophrenia in an exacerbation phase. IL-1ß, IL-2, IL-4, IL-6, BAFF, IFN-α, GM-CSF, NRG1-ß1, and GDNF increased but TNF-α and NGF-ß decreased in schizophrenia compared to healthy individuals. Subgroup analysis revealed the effect of sex, prevalent symptoms, and type of antipsychotic therapy on biomarker levels. Females, patients with predominantly negative symptoms, and those taking atypical antipsychotics had a more pro-inflammatory phenotype. Using cluster analysis, we classified participants into "high" and "low inflammation" subgroups. However, no differences were found in the clinical data of patients in these subgroups. Nevertheless, more patients (17% to 25.5%) than healthy donors (8.6% to 14.3%) had evidence of a pro-inflammatory condition depending on the clustering approach used. Such patients may benefit from personalized anti-inflammatory therapy.

Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis.

The cell-free DNA (cfDNA) levels are known to increase in biological fluids in various pathological conditions. However, the data on circulating cfDNA in severe psychiatric disorders, including schizophrenia, bipolar disorder (BD), and depressive disorders (DDs), is contradictory. This meta-analysis aimed to analyze the concentrations of different cfDNA types in schizophrenia, BD, and DDs compared with healthy donors. The mitochondrial (cf-mtDNA), genomic (cf-gDNA), and total cfDNA concentrations were analyzed separately. The effect size was estimated using the standardized mean difference (SMD). Eight reports for schizophrenia, four for BD, and five for DDs were included in the meta-analysis. However, there were only enough data to analyze the total cfDNA and cf-gDNA in schizophrenia and cf-mtDNA in BD and DDs. It has been shown that the levels of total cfDNA and cf-gDNA in patients with schizophrenia are significantly higher than in healthy donors (SMD values of 0.61 and 0.6, respectively; p < 0.00001). Conversely, the levels of cf-mtDNA in BD and DDs do not differ compared with healthy individuals. Nevertheless, further research is needed in the case of BD and DDs due to the small sample sizes in the BD studies and the significant data heterogeneity in the DD studies. Additionally, further studies are needed on cf-mtDNA in schizophrenia or cf-gDNA and total cfDNA in BD and DDs due to insufficient data. In conclusion, this meta-analysis provides the first evidence of increases in total cfDNA and cf-gDNA in schizophrenia but shows no changes in cf-mtDNA in BD and DDs. Increased circulating cfDNA in schizophrenia may be associated with chronic systemic inflammation, as cfDNA has been found to trigger inflammatory responses.

Multiplex Analysis of Serum Cytokine Profiles in Systemic Lupus Erythematosus and Multiple Sclerosis.

Changes in cytokine profiles and cytokine networks are known to be a hallmark of autoimmune diseases, including systemic lupus erythematosus (SLE) and multiple sclerosis (MS). However, cytokine profiles research studies are usually based on the analysis of a small number of cytokines and give conflicting results. In this work, we analyzed cytokine profiles of 41 analytes in patients with SLE and MS compared with healthy donors using multiplex immunoassay. The SLE group included treated patients, while the MS patients were drug-free. Levels of 11 cytokines, IL-1b, IL-1RA, IL-6, IL-9, IL-10, IL-15, MCP-1/CCL2, Fractalkine/CX3CL1, MIP-1a/CCL3, MIP-1b/CCL4, and TNFa, were increased, but sCD40L, PDGF-AA, and MDC/CCL22 levels were decreased in SLE patients. Thus, changes in the cytokine profile in SLE have been associated with the dysregulation of interleukins, TNF superfamily members, and chemokines. In the case of MS, levels of 10 cytokines, sCD40L, CCL2, CCL3, CCL22, PDGF-AA, PDGF-AB/BB, EGF, IL-8, TGF-a, and VEGF, decreased significantly compared to the control group. Therefore, cytokine network dysregulation in MS is characterized by abnormal levels of growth factors and chemokines. Cross-disorder analysis of cytokine levels in MS and SLE showed significant differences between 22 cytokines. Protein interaction network analysis showed that all significantly altered cytokines in both SLE and MS are functionally interconnected. Thus, MS and SLE may be associated with impaired functional relationships in the cytokine network. A cytokine correlation networks analysis revealed changes in correlation clusters in SLE and MS. These data expand the understanding of abnormal regulatory interactions in cytokine profiles associated with autoimmune diseases.

Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives.

The immune system is generally known to be the primary defense mechanism against pathogens. Any pathological conditions are reflected in anomalies in the immune system parameters. Increasing evidence suggests the involvement of immune dysregulation and neuroinflammation in the pathogenesis of schizophrenia. In this systematic review, we summarized the available evidence of abnormalities in the immune system in schizophrenia. We analyzed impairments in all immune system components and assessed the level of bias in the available evidence. It has been shown that schizophrenia is associated with abnormalities in all immune system components: from innate to adaptive immunity and from humoral to cellular immunity. Abnormalities in the immune organs have also been observed in schizophrenia. Evidence of increased C-reactive protein, dysregulation of cytokines and chemokines, elevated levels of neutrophils and autoantibodies, and microbiota dysregulation in schizophrenia have the lowest risk of bias. Peripheral immune abnormalities contribute to neuroinflammation, which is associated with cognitive and neuroanatomical alterations and contributes to the pathogenesis of schizophrenia. However, signs of severe inflammation are observed in only about 1/3 of patients with schizophrenia. Immunological parameters may help identify subgroups of individuals with signs of inflammation who well respond to anti-inflammatory therapy. Our integrative approach also identified gaps in knowledge about immune abnormalities in schizophrenia, and new horizons for the research are proposed.

Serum Cytokine Levels of Systemic Lupus Erythematosus Patients in the Presence of Concomitant Cardiovascular Diseases.

BACKGROUND: Systemic lupus erythematosus (SLE) is known to be associated with an increased risk of cardiovascular diseases (CVD). SLE patients suffer from CVD 3.5 times more often than healthy people. Cytokine-mediated inflammation is actively involved in the development of cardiovascular pathology. OBJECTIVE: Here, we analyzed serum levels of nine cytokines of steroids-treated SLE patients depending on the presence of concomitant CVD. METHODS: The levels of interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-10, IL-21, tumor necrosis factor α (TNFα), B-cell activating factor (BAFF), and a proliferation-inducing ligand (APRIL) were analyzed using multiplex immunoassay. RESULTS: In the total group of SLE patients (n=29), the concentrations of IL-6 and IL-10 were higher, and the APRIL level decreased compared to healthy donors (n=39, p<0.05). The same changes were observed in the group of patients without CVD (n=15); the levels of IL-6 and IL- 10 were found to be increased, and the level of APRIL was lower than in healthy individuals (p<0.05). In the group of SLE patients with CVD (n=14), the concentrations of IL-4, IL-6, IL- 10, and TNFα were found to be increased (p<0.05). Interestingly, the levels of TNFα and BAFF in SLE patients with CVD were higher than in patients without cardiovascular pathology. Thus, TNFα and BAFF levels were significantly altered in SLE with concomitant CVD compared to SLE without CVD. CONCLUSION: These findings suggest that cytokine profiles in SLE with concomitant CVD and SLE without CVD are different, which should be considered in further research with large samples.