Mar 22, 2018 8:00:00 AM
Summary of Kopczynska, M. et al; Complement system biomarkers in first episode psychosis. Schizophrenia Research, Dec 2017. Click here for the full article.
There has been debate over the past few years about the criteria currently used to classify patients with psychiatric disorders. The lack of objective and quantitative diagnostic criteria means that we rely on symptom-based categorization when deciding on patient classification and less on the underlying biology. Accumulating evidence suggests that inflammation and the immune system is the cause of such psychiatric disorders. The complement system is one such system, particularly the classical pathway, that potentially could be an important contributor.
Complement is a key driver of inflammation and complement dysregulation causes pathology in many diseases. The goal of this study was to investigate the potential for using complement-related proteins as serum biomarkers with prognostic and/or theranostic value. The concentrations of eleven complement analytes were measured using ELISA in 136 first episode psychosis (FEP) patients and 42 controls. Of the eleven analytes measured only one was significantly different between FEP and control populations, namely TCC.
The findings suggest that measurement of selected complement analytes interrogating the classical pathway could contribute to the early diagnosis of psychosis. A large study, planned prospectively, minimizing sample bias and using appropriately collected and stored EDTA plasma samples, is needed to confirm and extend the findings.
Mar 21, 2018 10:08:33 AM
Hycult Biotech is always eager to participate in research projects and to be the connection between science and industry by jointly developing tools for monitoring inflammatory and autoimmune diseases. As a participant in the RELENT (RELapses prevENTion in chronic autoimmune disease) consortium, Hycult Biotech has developed immunoassays that help monitor autoimmune disease and allow better treatment of these patients. More information about the RELENT consortium and what it stands for can be found in the following video:
Mar 1, 2018 4:30:00 AM
Summary of Zelek, W. et al; Measurement of soluble CD59 in CSF in demyelinating disease: evidence for an intrathecal source of soluble CD59. Mutiple Sclerosis, Feb 2018. Click here for the full article.
Activation of complement via the classical, lectin or alternative pathway leads to the formation of C3 convertase complexes that cleave C3 to C3a and C3b. C3b causes C5 convertase, which ultimately causes formation of the membrane attack complex (MAC) responsible for cell lysis. CD59 regulates formation of MAC by preventing recruitment of C9.
This study investigates the role of sCD59 in patients with demyelinating disorders. Cerebrospinal fluid (CSF) and matching plasma samples were taken from 78 patients with a demyelinating disorder and 34 from healthy controls. The concentration of sCD59 in these samples was measured using the Hycult Biotech sCD59 ELISA (HK374). An interesting finding was that sCD59 levels in CSF were approximately double those in matched plasma. The results further demonstrated that there was no significant difference in sCD59 levels between the various disease groups.
To determine the source of sCD59 in CSF, the study further performed immunohistochemical staining of brain sections. These results demonstrated that the choroid plexus is likely a site of abundant expression in the brain and may be a site of immune activation.
Whether the (relatively) high amounts of sCD59 in CSF are of any functional relevance remains to be demonstrated. In principle, sCD59 might contribute to homeostasis by dampening down complement activation in the CSF, but it is not a biomarker of demyelinating diseases.
Jan 25, 2018 4:00:00 AM
Summary of Westra, D. et al; Serological and genetic complement alterations in infection-induced and complement-mediated hemolytic uremic syndrome. Pediatric Nephrology 2017, 32(2). Click here for the full article.
The role of complement in the atypical form of hemolytic uremic syndrome (aHUS) has been extensively studied. However, less is known about the role of complement in infection-induced HUS. In a majority of these cases, the disease is triggered by an infection with Shiga-like toxin-producing Escherichia coli (STEC-HUS). Based on the similarity of the clinical manifestations of complement-mediated and infection-induced HUS, this study hypothesizes that also here the dysregulation of the complement system has an important place in the pathogenesis.
To determine the role of the alternative complement pathway (AP), 37 pediatric patients were enrolled in this study. 26 patients had STEC-HUS and 11 were diagnosed with aHUS. EDTA plasma was taken from the patients and used for testing a variety of complement factors and components, such as C3, CFH, CFI and TCC (Cat. # HK328). Results show that TCC was only significantly increased in STEC-HUS patients in the acute phase […] making it useful in monitoring the course of the disease. Taken all aspects together it is clear that measuring AP activation products, in particular C3d/C3 ratio, might help in monitoring disease activity and distinguishing between the different HUS etiologies. The exact role of altered complement activation in the pathogenesis of STEC-HUS, however, has not been fully elucidated.
Dec 6, 2017 2:30:00 AM
Summary of Treskes, N. et al; Diagnostic accuracy of novel serological biomarkers to detect acute mesenteric ischemia: a systematic review and meta-analysis. Internal and Emergency Medicine 12:6, 2017. Click here for the full article.
Acute mesenteric ischemia (AMI) is a rare but devastating medical condition with high mortality rates. Laparotomy remains the golden standard for diagnosis of AMI, but it is often unhelpful or too late. This meta-analysis aims to evaluate the diagnostic accuracy of novel serological biomarkers, including I-FABP. Thirteen studies containing 1,435 patients were examined in which I-FABP was used as a biomarker. The pooled sensitivity and specificity are 79.0% and 91.3% respectively.
Nov 10, 2017 7:00:00 AM
Oct 4, 2017 2:00:00 AM
Summary of Yamashiro, K et al; Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke. PLOS ONE 2017. Click here for the full article.
Metabolic disorders are one of the leading causes for heart disease and stroke. Increasing evidence suggests that dysbiosis is associated with metabolic diseases, but there is little known on the relation with ischemic stroke.
The aim of this study was to investigate whether the gut microbiota […] are altered in patients with ischemic stroke. Blood samples of 41 ischemic stroke patients were measured on a variety of metabolic readouts, but also cytokines and acute phase proteins were tested such as LBP (Cat. # HK315). Fecal samples were additionally used to examine the gut microbial composition with qPCR.
The results show that stroke patients had an impaired composition of the fecal bacteria and an elevated organic acid concentration. However, there were no differences in LBP concentrations, TNF-α levels and bacteremia rates between the patients with stroke and the control subjects.
Despite these findings, the data still suggests that gut dysbiosis in patients with ischemic stroke is associated with host metabolism and inflammation. Further studies are needed to determine a more predictive indicator of ischemic stroke.
Sep 21, 2017 7:50:00 AM
LPS (lipopolysaccharide), also known as endotoxins, are large heat-resistant and resilient molecules found on the outer membrane of Gram-negative bacteria and play an important role in the structural integrity of these bacteria. LPS triggers a strong immune response as Toll-like receptors (more specifically the CD14/TLR4/MD2 receptor complex) recognize LPS. They are an essential component of Gram-negative bacteria, making LPS a relevant target for new antimicrobial agents.
LPS comprises of three parts:
- Lipid A: a highly conserved lipid component
- The core oligosaccharide: attaches directly to lipid A and common to most variants
- The O antigen: a repetitive glycan polymer which maintain the hydrophilic properties of the molecule.
The recognition of LPS is a complex process that starts with the binding to LBP (LPS binding protein). This protein catalyzes the monomerization of LPS and transfers it to CD14 on the cell membrane and to lipoproteins. This in turn transfers it to MD-2, a non-anchored protein that is associated with the extracellular domain of TLR4. The triggering of TLR4 initiates a signaling cascade (MyD88) for cells to secrete pro-inflammatory cytokines and nitric oxide. TLR4 is commonly found on leukocytes and dendritic cells and generates an inflammatory response when exposed to LPS that includes but is not limited to:
- Production of cytokines such as IL’s and TNF’s
- Activation of the alternative complement pathway
- Activation of the coagulation cascade
These reactions can result in a physiological, pathological and clinical effects, such as fever, shock, leukopenia, hypoglycemia and even death. In the past it was thought that LPS exposure is the main cause for pathological conditions, such as sepsis and autoimmune diseases. Advancing insights demonstrate that also the host pathogen interaction plays an important role as it can cause disease due to disruption of the homeostatic state. There are many scientific publications that underline this theory with topics such as:
- The gut microbiome in conjunction with microbial translocation
- Periodontal disease in relation to the development of heart disease
Even though it is one of the most widely described molecules in scientific literature, its role in both homeostasis and pathology keeps expanding.
For more information on Hycult Biotech products related to the above, please take a look at the following literature:
- LPS and microbial toxins folder
- TLR and inflammasome folder
- Product page: LAL Chromogenic Endpoint Assay
You can also visit the products section on the Hycult Biotech website via: https://www.hycultbiotech.com/products
Aug 29, 2017 4:00:00 AM
Summary of Ahout, I et al; Prospective observational study in two Dutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children. BMJ Open 2017. Click here for the full article.
Lower respiratory tract infections (LRTIs) are a major cause of hospital admissions in children. Viruses are the most common cause and the course of these infections is unpredictable with potential fast deterioration into respiratory failure. Currently, it is difficult to improve clinical judgement on aspects such as length of hospitalization and ICU admission due to the fact that this is generally based on subjective criteria. The aim of this study was to determine whether systemic inflammatory markers can be used to predict severity of disease in children with respiratory viral infections.
Blood was collected from 104 children <3 years of age with viral LRTI in an acute setting (within 24 hours) and in the recovery phase (4-6 weeks). Plasma protein levels of SAA, SAP, PTX3, properdin and CRP were determined by ELISA to investigate potential indicators of disease severity.
The results demonstrated that plasma levels of CRP, SAP, SAA and PTX3 increased significantly during the acute phase. Properdin levels did not differ between the acute phase and the recovery phase, but it did drop significantly in patients with severe disease. SAA levels were significantly elevated in relation to disease severity. Additionally, both CRP and properdin correlated significantly with duration of hospitalization.
This study has proven the clinical relevance of plasma markers such as CRP, PTX3, SAA and properdin in children with acute viral LRTI. However, a combination of these markers significantly enhances the accuracy of identifying patients with severe disease […] and might provide additive value in clinical decision-making.
Jul 20, 2017 10:09:57 AM
Summary of Giloteaux, L et al; Reduced diversity and altered composition of the gut microbiome in individuals with ME/CFS. Microbiome 2016. Click here for the full article.
Gastrointestinal disturbances are one of the symptoms most commonly reported in patients with myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS). This study assesses the microbial diversity and inflammatory status of these patients.
49 ME/CFS patients and 39 controls were tested for LBP (Cat. # HK315) as a marker for microbial translocation and I-FABP (Cat. # HK406) as a marker for gastrointestinal tract damage. The results conclude that ME/CFS patients had significantly higher plasma LPS levels than healthy individuals but that the difference in I-FABP levels was not statistically significant. Sequencing of the stool microbiota also showed lower relative abundance of Firmicutes and higher relative abundance of Proteobacteria in ME/CSF samples. It was also observed that members of the Ruminococcaeae and Bifidobacteriaceae were significantly increased in healthy individuals.
Taken together, the study suggests that ongoing damage to the gut mucosa leads to increased microbial translocation in ME/CSF, which in turn could alter antimicrobial regulators and dysregulate the innate immune system. The combination of identifying an altered commensal gut microbiota with the right inflammatory markers could lead to novel diagnostics and therapeutic strategies that would improve clinical outcome.