Concentrations Of Complement Components Research Articles

The Depth of the Molecular Response in Patients with Chronic Myeloid Leukemia Correlates with Changes in Humoral Immunity.

Background and Objectives: The effective treatment of chronic myeloid leukemia leads to the restoration of proper immune system function. We aimed to investigate fluctuations in circulating cytokines, angiogenic factors and complement components in patients with CML during the first year of treatment with TKI and correlate them with the degree of achieved molecular response. Material and Methods: We recruited 31 patients with newly diagnosed CML. Peripheral blood and bone marrow samples were obtained, and concentrations of serum proteins were measured using an immunology multiplex assay. Results: The study cohort was divided into two groups of optimal or non-optimal in accordance with the European Leukemia Net (ELN) guidelines. We found significantly higher concentrations of C1q, C4 and C5a in serum after 3 months of TKI treatment in patients who achieved optimal responses in the 6 months after diagnosis. The most alterations were observed during 12 months of therapy. Patients in the optimal response group were characterized by higher serum concentrations of TGF-β, EGF, VEGF, Angiopoietin 1, IFN-γ and IL-8. Conclusions: The later plasma concentrations of complement components were significantly increased in patients with optimal responses. The changes after 12 months of treatment were particularly significant. Similar changes in bone marrow samples were observed.

Complement System Deficiencies in Elite Athletes.

Although regular physical activity improves immune competency and reduces the prevalence of inflammatory diseases, strenuous training in elite athletes is associated with an increased susceptibility to infectious complications. Therefore, the objective of our study was to assess the routinely examined parameters of the complement system in elite athletes. The study was carried out in a cohort of elite athletes (n = 134) and healthy control subjects (n = 110). In all subjects, besides a routine laboratory check-up, serum concentrations of the C3 and C4 complement components, mannose-binding lectin (MBL), as well as activation of all three complement pathways were determined. Compared to healthy controls, lower C3 and C4 complement component concentrations were observed in elite athletes (0.96 ± 0.1 vs. 1.08 ± 0.2mg/L, and 0.18 ± 0.1 vs. 0.25 ± 0.1mg/L, respectively, p < 0.05); with much higher frequency rates of C3 and C4 deficiencies in athletes (31.3 vs. 14.5%, and 6 vs. 0%, p < 0.05). Simultaneously, athletes had much higher frequency rates of deficiencies of activation of classical and alternative complement pathways; while, deficiency of activation of the lectin pathway was similar in both cohorts. We confirmed a high frequency of defects in the complement system in elite athletes. Lower concentrations of C3 and C4 complement components, with high frequencies of deficiencies of the classical and alternative complement activation pathways were the most prevalent disorder of the complement system in elite athletes. Further studies are needed to uncover the functional impacts of these observations upon the susceptibility to infectious diseases.

Is the central complement component C3 altered in the synergy of HIV infection and preeclampsia?

ObjectiveIn light of complement activation in preeclampsia and HIV infection, this study evaluates the concentration of complement component 3 (C3) in HIV-associated preeclampsia. MethodThe study population (n = 76) was equally stratified by pregnancy type (normotensive pregnant and preeclampsia) and by HIV status (HIV positive and HIV negative). The plasma concentration of C3 was determined using a Bioplex immunoassay procedure. ResultsWe report a significant increase in C3 concentration in the HIV-negative versus the HIV-positive groups (p < 0.05), regardless of pregnancy type. However, based on pregnancy type and irrespective of HIV status, C3 concentration was similar between normotensive versus preeclampsia. Concentration of C3 was significantly increased in the HIV-positive preeclamptic compared HIV-negative preeclamptic groups (p = 0.04). The correlation of C3 with all study groups was non-significant. ConclusionThis study demonstrates that C3 was upregulated in HIV-associated PE compared to HIV- associated normotensive pregnancies. The dysregulation of C3 expression by HIV infection may be attributed to antiretroviral therapy.

Polygenic risk score and biochemical/environmental variables predict a low-risk profile of age-related macular degeneration in Sardinia.

To ascertain the prevalence and clinical and genetic features of age-related macular degeneration (AMD) in subjects living in the Lanusei valley, Central Sardinia, Italy, involved in a study on ageing (SardiNIA project). A total of 814 volunteers aged ≥ 50years, randomly selected from the SardiNIA project dataset, were included. A color fundus (CF) photograph of the 30° central retina of each eye was obtained and graded according to the Age-Related Eye Disease Study system. Life-style choices were investigated using standardized questionnaires. The concentrations of several inflammatory biomarkers (i.e., complement component, fibrinogen, and C-reactive protein) were measured. Polygenic risk score (PRS) was calculated and compared with results obtained from a European cohort. A total of 756 subjects had gradable CF photographs for AMD detection. In 91.3%, no signs of AMD were observed. The prevalence rates of early and late AMDs were 6.9% and 0.6%, respectively. A total of 85% of subjects were physically active; only 13.5% were current smokers. Low concentrations of complement component, fibrinogen, and C-reactive protein were found. We calculated the polygenic risk scores (PRS) using 40 AMD markers distributed on several candidate genes in Europeans and Sardinians. The mean PRS value was significantly lower in Sardinians than in the Europeans (0.21 vs. 0.248, respectively, p = 1.18 × 10-77). In our cohort, most subjects showed no sign of any AMD type and late AMD was a condition rarely observed. Results of genetic, biochemical, and life-style investigation support the hypothesis that Sardinia population may present of a peculiar background with a protective effect against AMD development.

Associations between the Nutrient Profiling System Underlying the Nutri-Score Nutrition Label and Biomarkers of Chronic Low-Grade Inflammation: A Cross-Sectional Analysis of a Middle- to Older-Aged Population.

Low-grade systemic inflammation is associated with a range of conditions. Diet may modulate inflammation and public health strategies are needed to guide consumers’ dietary choices and help prevent diet-related disease. The Food Standards Agency nutrient profiling system (FSAm-NPS) constitutes the basis of the five-colour front-of-pack Nutri-Score labelling system. No study to date has examined FSAm-NPS dietary index associations with biomarkers of inflammation. Therefore, our objective was to test relationships between the FSAm-NPS and a range of inflammatory biomarkers in a cross-sectional sample of 2006 men and women aged 46–73 years. Individual participant FSAm-NPS scores were derived from food frequency questionnaires. Pro-inflammatory cytokine, adipocytokine, acute-phase response protein, coagulation factor and white blood cell count concentrations were determined. Correlation and linear regression analyses were used to examine FSAm-NPS relationships with biomarker levels. In crude and adjusted analyses, higher FSAm-NPS scores, reflecting poorer nutritional quality, were consistently and positively associated with biomarkers. In fully adjusted models, significant associations with concentrations of complement component 3, c-reactive protein, interleukin 6, tumour necrosis factor alpha, resistin, white blood cell count, neutrophils, eosinophils and the neutrophil-to-lymphocyte ratio persisted. These results suggest that dietary quality, determined by Nutri-Score rating, is associated with inflammatory biomarkers related to health.

Evaluation of Haemolytic Activity in Smokers by Using Non-Linear Regression.

&lt;b&gt;Background and Objective:&lt;/b&gt; Smokers are poorly protected against pathogens. Many studies have focused on the concentrations of complement components in comparison to smokers while ignoring the practical sequencing of complement components. There are numerous methods for estimating haemolytic activity (CH50%), all of which need a large number of samples and dilution, in addition to a typically expensive test kit. This novel study attempts to use statistical analysis and use the non-linear regression 'power equation' to extract the CH50% by using 5 serum dilutions only. &lt;b&gt;Materials and Methods:&lt;/b&gt; The power equation can multiply the five practical dilutions into hundreds of mathematical loops within the sample range. The (CH50%) value is highly accurate for both the study and comparison sample and was evaluated in11 smokers. &lt;b&gt;Results:&lt;/b&gt; The results were contrasted with a control composed of 11 individuals, matched by age and sex. The power equation showed a 6.48% significant reduction in (CH50%) in smokers compared with non-smokers, where a 17.54% reduction was observed. &lt;b&gt;Conclusion:&lt;/b&gt; The current study suggests a decrease in the function of the classical complement pathway (CH50%) in smokers. On the other hand, the study provided a new statistical pattern, linking the practical values with default values within the range of dilution and formulating an equation that could be used to extract the value of CH50% with high accuracy.

No Evident Systemic Terminal Complement Pathway Activation in Hidradenitis Suppurativa

No Evident Systemic Terminal Complement Pathway Activation in Hidradenitis Suppurativa

Evaluation of electroacupuncture for symptom modification in a rodent model of spontaneous osteoarthritis.

Faced with the frustration of chronic discomfort and restricted mobility due to osteoarthritis (OA), many individuals have turned to acupuncture for relief. However, the efficacy of acupuncture for OA is uncertain, as much of the evidence is inconclusive. The purpose of this study was to evaluate electroacupuncture (EA) in a rodent model of OA such that conclusions regarding its effectiveness for symptom or disease modification could be drawn. Ten 12-month-old male Hartley guinea pigs-which characteristically have moderate to advanced OA at this age-were randomly assigned to receive EA for knee OA (n = 5) or anesthesia only (control group, n = 5). Treatments were performed three times weekly for 3 weeks, followed by euthanasia 2 weeks later. Gait analysis and enclosure monitoring were performed weekly to evaluate changes in movement. Serum was collected for inflammatory biomarker testing. Knee joints were collected for histology and gene expression. Animals receiving EA had significantly greater changes in movement parameters compared to those receiving anesthesia only. There was a tendency toward decreased serum protein concentrations of complement component 3 (C3) in the EA group compared to the control group. Structural and antioxidant gene transcripts in articular cartilage were increased by EA. There was no significant difference in total joint histology scores between groups. This study provides evidence that EA has a positive effect on symptom, but not disease, modification in a rodent model of OA. Further investigations into mechanistic pathways that may explain the efficacy of EA in this animal model are needed.

Short Course of Eculizumab May Be Effective in Dialysis-Dependent Transplantation-Associated Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplantation: A Case Report

BackgroundAllogeneic hematopoietic stem cell transplantation (alloHSCT) could induce several complications. The most frequent viral infections and graft-vs-host disease (GvHD) sometimes lead to thrombotic microangiopathy (TMA). It is associated with significant morbidity and mortality with the risk of death reaching 90%. Effective prevention and treatment are not available to date. Recent attempts at using antibody against C5 have been made. Case reportA 19-year-old girl with acute myeloid leukemia twice underwent alloHSCTs from her 10/10 HLA-matched sister. After the second HSCT severe acute steroid-resistant grade 4 GvHD occurred. Despite treatment with high doses of steroids, mycophenolate mofetil, biological therapy, and extracorporeal photopheresis, the patient developed TMA with acute kidney injury and the need for renal replacement therapy. The concentration of complement component 3 and activity of ADAMTS 13 were normal, and infection with Escherichia coli (E. coli) 0157H7 was excluded. Due to failure of all ordered therapies and severity of the condition, an attempt was taken to use eculizumab. Two 900-mg doses of eculizumab (Soliris) were administered at an interval of 2 weeks, which resulted in the improvement of renal function and amelioration of hemolysis and thrombocytopenia. Dialysis therapy was finished after 5 weeks, and then a third dose of the drug was administered. Eighteen months later, the patient is alive and well, with limited chronic GvHD. eGFR remains stable at 40 to 46 mL/min/1.73 m2, and mild hypertension requires treatment with angiotensin converting enzyme inhibitors and furosemide. ConclusionEven a short course of eculizumab can be sufficient in controlling the TMA after HSCT, provided that the TMA-triggering factors are well controlled.

Аpplication of plasma proteins cryoheparinoprecipitation method in the treatment of patients with cryoglobulinemia

Introduction.The term “cryoglobulinemia” is currently used to identify immunoglobulins in vitro in the blood serum that precipitate at temperatures below 37 °C; in vivo they form immune complexes that can be deposited in small vessels and activate the complement system with the development of leukocytoclastic vasculitis. Cryoglobulinemia may develop in various lymphoproliferative, autoimmune and infectious diseases.Aim of study.To develop the technique of plasma proteins cryofraction (selective plasmapheresis with the use of heparin as a stimulant of fibronectin opsonic activity and purified autoplasma to compensate for the removed volume), to evaluate the effectiveness and tolerability of the developed technique in the treatment of patients with cryoglobulinemia.Materials and methods.159 patients were treated (120 women and 39 men aged 21 to 83 years).Research results.Heparinocryofraction technique is a highly effective method of extracorporeal blood purification, which allows to selectively remove from the patients’ plasma such pathological components as cryoglobulins (up to 100% of the initial content), adhesive proteins (up to 84% of the initial content), fibronectin and immune complexes (up to 7% of the initial content). It is possible to reduce significantly and reliably the level of cryoglobulins, circulating immune complexes, non-specific markers of inflammation, daily proteinuria, as well as to normalize the initially reduced concentration of complement components and hemoglobin in the blood of patients with cryoglobulinemia before and after the procedure of cryofractionation. Purified by the proposed method autoplasma is a solution of albumin and normal immunoglobulins, which allows to use it for plasma substitution during a course of cryofractionation procedures, on average 7 procedures with an interval of 1–2 days.Conclusion.The technique of cryofractionation using heparin and purified autoplasma can and should be widely used in the complex treatment of patients with cryoglobulinemia. Carrying out 6–-7 sessions of plasma cryofractionation allows to remove cryoglobulins from plasma effectively and selectively. Application of purified autoplasma allows to avoid using of blood preparations in plasmapheresis. The proposed method allows to significantly improve the efficiency and tolerance of medication therapy and increase the duration of disease remission.

The TLRs and IFNs in patients with connective tissue diseases

Autoimmune connective tissue diseases (ACTD) are characterized by spontaneous stimulation of the immune system and the production of autoantibodies. Some autoantibodies may create an immune complex with DNA and/or RNA and promote tissue inflammation. Immune complexes that contain nucleic acids can act as ligands for endosomal Toll-like receptors (TLR), which activation induces secretion of the type I and type III interferons. The present study aimed to determine whether TLRs and IFNs genes could be considered as potential ACTD biomarkers. IFN-A and IFN-G showed a relationship with a predisposition to the development of SLE and MCTD, and IFN-B with a predisposition to the development of SLE. The TLR7 rs5743305 T allele and rs5743316 A allele may play a protective role against the development of MCTD, and the TLR7 rs1731479 T allele and TLR8 rs17256081 C allele may be predictors of MCTD development. mRNA expression of the IFN-α, IFN-β, IFN-γ, TLR3, TLR8 and TLR7 was significantly higher in patients with SLE compared to patients with MCTD and SSc. MCTD patients with anti-U1-70k (+) had higher IFN-γ and lower IFN-β serum levels than patients without this antibody. In patients with SLE, serum levels of IFN-α and IFN-γ correlate with the concentration of complement components, and serum levels of IFN-α with disease activity. The study confirmed that the TLR-IFN pathway may be considered as an important pathogenic mechanism for ACTD.

Baseline high levels of complement component 4 predict worse clinical outcome at 1-year follow-up in first-episode psychosis

BackgroundRecent evidence has highlighted the potential role of complement component 4 (C4) in the development of schizophrenia. However, it remains unclear whether C4 is also relevant for clinical outcome and if it could be considered a possible therapeutic target. The aim of this naturalistic longitudinal study was to investigate whether baseline levels of C4 predict worse clinical outcome at 1-year follow-up in patients with first episode psychosis. MethodsTwenty-five patients with first episode psychosis were assessed at baseline and followed-up prospectively for their clinical outcome at 1 year from baseline assessment. Concentrations of complement component 4 (C4) were measured using ELISA methods from baseline serum samples. Twelve patients were classified as non-responders and 13 as responders. ANCOVA analyses were conducted to investigate differences in baseline C4 levels between responders and non-responders at 1-year covarying for baseline severity of symptoms and for levels of C reactive protein. ResultsNon-responders show significantly higher baseline C4 levels compared with responders when controlling for baseline psychopathology and baseline levels of C reactive protein (552.5 ± 31.3 vs 437.6 ± 25.5 mcg/ml; p = 0.008). When investigating the ability of C4 levels to distinguish responders from non-responders, we found that the area under the ROC curve was 0.795 and the threshold point for C4 to distinguish between responders and non-responders appear to be around 490 mcg/ml. ConclusionsOur preliminary findings show that baseline C4 levels predict clinical outcome at 1-year follow-up in patients with first episode psychosis.

Interleukin-1 receptor antagonist treatment in acute ischaemic stroke does not alter systemic markers of anti-microbial defence.

Background: Blockade of the cytokine interleukin-1 (IL-1) with IL-1 receptor antagonist (IL-1Ra) is a candidate treatment for stroke entering phase II/III trials, which acts by inhibiting harmful inflammatory responses. Infection is a common complication after stroke that significantly worsens outcome and is related to stroke-induced deficits in systemic immune function thought to be mediated by the sympathetic nervous system. Therefore, immunomodulatory treatments for stroke, such as IL-1Ra, carry a risk of aggravating stroke-associated infection. Our primary objective was to determine if factors associated with antibody-mediated antibacterial defences were further compromised in patients treated with IL-1Ra after stroke. Methods: We assessed plasma concentrations of immunoglobulin isotypes and complement components in stroke patients treated with IL-1Ra or placebo and untreated non-stroke controls using multiplex protein assays. Activation of the sympathetic nervous system (SNS) was determinedby measuring noradrenaline, a major SNS mediator. Results: There were significantly lower plasma concentrations of IgM, IgA, IgG1 and IgG4 in stroke-patients compared to non-stroke controls, however there were no differences between stroke patients treated with placebo or IL-1Ra. Concentrations of complement components associated with the classical pathway were increased and those associated with the alternative pathways decreased in stroke patients, neither being affected by treatment with IL-1Ra. Noradrenaline concentrations were increased after stroke in both placebo and IL-1Ra-treated stroke patients compared to non-stroke controls. Conclusion: These data show treatment with IL-1Ra after stroke does not alter circulating immunoglobulin and complement concentrations and is therefore unlikely to further aggravate stroke-associated infection susceptibility through altered availability of these key anti-microbialmediators.

Interleukin-1 receptor antagonist treatment in acute ischaemic stroke does not alter systemic markers of anti-microbial defence

Background: Blockade of the cytokine interleukin-1 (IL-1) with IL-1 receptor antagonist (IL-1Ra) is a candidate treatment for stroke entering phase II/III trials, which acts by inhibiting harmful inflammatory responses. Infection is a common complication after stroke that significantly worsens outcome and is related to stroke-induced deficits in systemic immune function thought to be mediated by the sympathetic nervous system. Therefore, immunomodulatory treatments for stroke, such as IL-1Ra, carry a risk of aggravating stroke-associated infection. Our primary objective was to determine if factors associated with antibody-mediated antibacterial defences were further compromised in patients treated with IL-1Ra after stroke. Methods: We assessed plasma concentrations of immunoglobulin isotypes and complement components in stroke patients treated with IL-1Ra or placebo and untreated non-stroke controls using multiplex protein assays. Activation of the sympathetic nervous system (SNS) was determined by measuring noradrenaline, a major SNS mediator. Results: There were significantly lower plasma concentrations of IgM, IgA, IgG1 and IgG4 in stroke-patients compared to non-stroke controls, however there were no differences between stroke patients treated with placebo or IL-1Ra. Concentrations of complement components associated with the classical pathway were increased and those associated with the alternative pathways decreased in stroke patients, neither being affected by treatment with IL-1Ra. Noradrenaline concentrations were increased after stroke in both placebo and IL-1Ra-treated stroke patients compared to non-stroke controls. Conclusion: These data show treatment with IL-1Ra after stroke does not alter circulating immunoglobulin and complement concentrations and is therefore unlikely to further aggravate stroke-associated infection susceptibility through altered availability of these key anti-microbial mediators.

Interleukin-1 receptor antagonist treatment in acute ischaemic stroke does not alter systemic markers of anti-microbial defence.

Background: Blockade of the cytokine interleukin-1 (IL-1) with IL-1 receptor antagonist (IL-1Ra) is a candidate treatment for stroke entering phase II/III trials, which acts by inhibiting harmful inflammatory responses. Infection is a common complication after stroke that significantly worsens outcome and is related to stroke-induced deficits in systemic immune function thought to be mediated by the sympathetic nervous system. Therefore, immunomodulatory treatments for stroke, such as IL-1Ra, carry a risk of aggravating stroke-associated infection. Our primary objective was to determine if factors associated with antibody-mediated antibacterial defences were further compromised in patients treated with IL-1Ra after stroke. Methods: We assessed plasma concentrations of immunoglobulin isotypes and complement components in stroke patients treated with IL-1Ra or placebo and untreated non-stroke controls using multiplex protein assays. Activation of the sympathetic nervous system (SNS) was determinedby measuring noradrenaline, a major SNS mediator. Results: There were significantly lower plasma concentrations of IgM, IgA, IgG1 and IgG4 in stroke-patients compared to non-stroke controls, however there were no differences between stroke patients treated with placebo or IL-1Ra. Concentrations of complement components associated with the classical pathway were increased and those associated with the alternative pathways decreased in stroke patients, neither being affected by treatment with IL-1Ra. Noradrenaline concentrations were increased after stroke in both placebo and IL-1Ra-treated stroke patients compared to non-stroke controls. Conclusion: These data show treatment with IL-1Ra after stroke does not alter circulating immunoglobulin and complement concentrations and is therefore unlikely to further aggravate stroke-associated infection susceptibility through reduced availability of these key anti-microbialmediators.

Improvements in humoral immune function and glucolipid metabolism after laparoscopic sleeve gastrectomy in patients with obesity

BackgroundObesity is associated with impaired immunity and chronic, low-grade inflammation, but little is known about the immune system’s response to bariatric surgery–induced weight loss. ObjectivesTo determine whether circulating immunoglobulins and acute-phase reactant levels are altered after bariatric surgery. SettingUniversity Hospital, China. MethodsFifty-eight patients with obesity were recruited from the Second Xiangya Hospital of Central South University; 48 underwent laparoscopic sleeve gastrectomy and 10 underwent traditional medical therapy. ResultsDuring the 12-month follow-up, bariatric surgery showed pronounced effects on weight loss and glucose and lipid metabolism. Circulating concentrations of hypersensitive C-reactive protein, and complement components 3 and 4 decreased significantly. Compared with the presurgery level, the immunoglobulin A, immunoglobulin M, and immunoglobulin G levels increased significantly at 2 and 6 months postsurgery. Compared with the whole group, the same results were observed after surgery in the circulating concentrations of complement components 3 and 4 and hypersensitive C-reactive protein in patients with class I obesity. However, the immunoglobulin G concentration increased at 6 and 12 months postsurgery, immunoglobulin A increased at 12 months postsurgery, and no postsurgery changes in immunoglobulin M were found in patients with class I obesity. No significant changes were noted in patients who underwent traditional medical therapy. We also found a correlation between decreased complement factor levels and improved insulin sensitivity. ConclusionsIn addition to reducing weight and controlling diabetes and dyslipidemia, bariatric surgery is also effective for improving the immune function of patients with obesity.

Complement component consumption in sepsis correlates better with hemostatic system parameters than with inflammatory biomarkers

IntroductionThe aim of this study was to investigate the role of C3 and C4 complement components in prediction of sepsis outcome. The secondary aim was to determine relationship between complement components and other inflammatory parameters, and parameters of hemostasis. MethodsOne-hundred-thirty-seven patients with sepsis (Sepsis-3 criteria) were included in the study. Routine laboratory markers, predictive APACHEII and SOFA scores, concentrations of C3 and C4, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin (AT), protein C (PC), protein S (PS), endogenous thrombin potential (ETP), thrombomodulin, and D-dimer were available. Concentrations of C3 and C4 were correlated with the disease outcome, predictive scores, inflammatory markers and parameters of hemostasis. Statistical analysis was performed using the non-parametric approach and significance was set at p < 0.05. ResultsA significant depletion of the complement was observed in non-survivors (AUCROCC3 = 0.692, pC3 < 0.001,AUCROCC4 = 0.672, pC4 = 0.001). There was a significant negative correlation of C3and C4with APACHEII and SOFA (C3-APACHEII ρ = −0.364, p = 0.011, C3-SOFA ρ = −0.460, p < 0.001), aPTT (ρ = −0.407, p < 0.001), PT (ρ = −0.408, p < 0.001), and D-dimer (ρ = −0.274, p = 0.001). A significant positive correlation was observed with natural anticoagulants (C3-AT ρ = 0.493, p < 0.001; C3-PC ρ = 0.450, p < 0.001; C3-PS ρ = 0.345, p < 0.001), fibrinogen (ρ = 0.481, p < 0.001),and ETP (ρ = 0.384, p < 0.001). C3 and C4 correlated significantly only with CRP (ρ = 0.207, p = 0.015), while no significant correlations with procalcitonin and WBC were detected. Results were similar for C4 and C3, although C3 presented higher correlation coefficients. ConclusionIn septic patients with poorer outcome, a significant depletion of the complement system was observed. Concentrations of complement components demonstrated stronger correlations with coagulation parameters than with inflammatory biomarkers.

136. Increased Expression of Early Complement Components in Frontal Cortex in Schizophrenia

Background: The complement system is a key effector of innate immunity, mediating elimination of pathogens and debris via initiation of phagocytosis, inflammation, and cell lysis. Intriguingly, recent studies have identified an additional role for early complement components, including C1q, C3, and C4, in synaptic pruning and remodeling. Mounting evidence suggests that dysregulation of the complement system occurs in schizophrenia. Increased activation and concentration of complement components has been reported in blood, while complement C4 was recently identified as a major genetic risk factor. However, little is known about expression of complement components in brain tissue in this disorder. The aim of this study was therefore to compare protein and mRNA expression of early complement components in frontal cortex in schizophrenia and control subjects. Methods: Protein and/or mRNA expression of the early complement components C1q, C3 and C4, and the regulator C1-inhibitor, was quantified in 35 individuals with SCZ and 35 controls. Samples were obtained from the orbital–frontal and dorsolateral prefrontal regions courtesy of the Stanley Medical Research Institute. Proteins were quantified in dorsolateral prefrontal cortex by immunoblotting, and mRNA expression measured in orbital–frontal cortex using quantitative PCR. Measures were compared between groups using analysis of variance. Results: C1-inhibitor was higher in the schizophrenia group. While C4 mRNA expression was increased in schizophrenia, C4 protein levels did not differ between groups, despite the presence of a positive correlation between protein and mRNA expression. Of note, C4 genotype was associated with C4 protein levels. Furthermore, C4 protein levels were negatively correlated with levels of the synaptic protein SNAP-25. Finally, positive correlations were observed between early complement components and markers of peripheral and/or central inflammation. Conclusion: Overall, our results are consistent with a dysregulation of the complement system in schizophrenia. Increased complement expression may be indicative of an inflammatory response. However, early complement components have also been implicated in synaptic pruning and circuit remodeling. Observed correlations between complement C4 and SNAP-25 suggest the complement system may play a role in triggering the synaptic disturbances previously identified in schizophrenia. Funding: This work was supported by the Canadian Institutes of Health Research.

Mobilization of Peripheral Blood Stem Cells and Changes in the Concentration of Plasma Factors Influencing their Movement in Patients with Panic Disorder

In this paper we examined whether stem cells and factors responsible for their movement may serve as new biological markers of anxiety disorders. The study was carried out on a group of 30 patients diagnosed with panic disorder (examined before and after treatment), compared to 30 healthy individuals forming the control group. We examined the number of circulating HSCs (hematopoetic stem cells) (Lin−/CD45 +/CD34 +) and HSCs (Lin−/CD45 +/AC133 +), the number of circulating VSELs (very small embryonic-like stem cells) (Lin−/CD45−/CD34 +) and VSELs (Lin−/CD45−/AC133 +), as well as the concentration of complement components: C3a, C5a and C5b-9, SDF-1 (stromal derived factor) and S1P (sphingosine-1-phosphate). Significantly lower levels of HSCs (Lin−/CD45 +/AC133 +) have been demonstrated in the patient group compared to the control group both before and after treatment. The level of VSELs (Lin−/CD45−/CD133 +) was significantly lower in the patient group before treatment as compared to the patient group after treatment.The levels of factors responsible for stem cell movement were significantly lower in the patient group compared to the control group before and after treatment. It was concluded that the study of stem cells and factors associated with their movement can be useful in the diagnostics of panic disorder, as well as differentiating between psychotic and anxiety disorders.

Influence of Duration of Heroin Dependence on Humoral Immunologic Indicators.

The incidence of autoantibodies may be associated with the duration of drug use. In this study, we assessed the association between the duration of heroin dependence and various humoral immunologic indicators, including IgA, IgG, IgM, complement component 3, complement component 4, rheumatoid factor, anti-β2-glycoprotein 1 (IgA, IgG, IgM), antinuclear antibody, circulating immune complexes, and cryoglobulins. A total of 363 patients with heroin dependence were enrolled in this cross-sectional and prospective study over a 3.5-year period. Depending on the duration of heroin use, participants were divided into 3 groups: up to 3 years, 4 to 7 years, and more than 7 years of heroin dependence. All patients were analyzed for the indicators. There was a significant difference between the duration of heroin dependence and increased concentration of IgA (P = 0.0000), IgG (P = 0.0000), IgM (P = 0.0001), complement component 3 (P = 0.042), rheumatoid factor (P = 0.0001), anti-β2-glycoprotein 1 (IgA, P = 0.0098; IgG, P = 0.0000; IgM, P = 0.0000), the presence of antinuclear antibody (P = 0.01) and cryoglobulins (P = 0.0000), and decreased concentration of complement component 4 (P = 0.002). There was no significant difference in circulating immune complex concentration (P = 0.097). A longer duration of heroin dependence was associated with increased concentrations of IgA, IgG, IgM, complement component 3, rheumatoid factor, anti-β2-glycoprotein 1 (IgA, IgG, IgM), presence of antinuclear antibodies and cryoglobulins, and decreased concentrations of complement component 4, but there was no influence on circulating immune complex values.