Stability of pro- and anti-inflammatory immune biomarkers for human cohort studies.
Graham C,Chooniedass R,Stefura W P,Lotoski L,Lopez P,Befus A D,Becker A B,HayGlass K T
Journal of translational medicine
BACKGROUND:Although discovery research has identified the importance of dozens of pro- and anti-inflammatory immune mediators in the pathogenesis, maintenance, exacerbation and resolution of inflammatory diseases, most human cohort studies have incorporated few or no immunological intermediate phenotypes in their analyses. Significant hindrances have been (1) the limited panel of biomarkers known to be readily detected in healthy human populations and (2) the stability, hence utility, of such biomarkers to repeated analysis. METHODS:The frequency and stability of 14 plasma biomarkers linked to in vivo immune regulation of allergic and autoimmune inflammatory disorders was determined in 140 healthy pediatric and adult participants. The impact of initial and multiple subsequent freeze/thaw cycles on pro-inflammatory (CCL2, CXCL10, IL-18, TNFα, IL-6), anti-inflammatory (IL-10, sTNF-RII, IL-1Ra), acute phase proteins (CRP, PTX3) and other biomarkers (sST2, IL-1RAcP) was subsequently quantified. RESULTS:Multiple biomarkers capable of providing an innate immune signature of inflammation were readily detected directly ex vivo in healthy individuals. These biomarker levels were unaffected when comparing paired data sets from freshly obtained, never frozen plasma or serum and matched aliquots despite extensive freeze/thaw cycles. Neither age nor sex affected stability. Similarly, no quantitative differences were found following repetitive analysis of inflammatory biomarkers in culture samples obtained following in vitro stimulation with TLR and RLR ligands. CONCLUSIONS:A broad panel of in vivo and ex vivo cytokine, chemokine and acute phase protein biomarkers that have been linked to human chronic inflammatory disorders are readily detected in vivo and remain stable for analysis despite multiple freeze thaw cycles. These data provide the foundation and confidence for large scale analyses of panels of inflammatory biomarkers to provide better understanding of immunological mechanisms underlying health versus disease.
10.1186/s12967-017-1154-3
[Useful biological markers in the diagnosis of autoimmune status].
Vlad Claudia,Dumitrescu Mihnea,Nica Luciana,Niţa Genoveva
Bacteriologia, virusologia, parazitologia, epidemiologia (Bucharest, Romania : 1990)
UNLABELLED:Immune function is essential for human beings, the severe disorders of the immune system being incompatible with survival. The immune system is perfectly organized to fulfill its essential function: to distinguish self from nonself Perfect state of immune tolerance to self components is disturbed in some cases in which the immune system no longer tolerates the self and summarizes the production of autoantibodies or autoreactive lymphocytes occurrence. The purpose of this study was the determination of biological markers in groups of patients with certain conditions, in order to establish correlations between these parameters and certain pathological events, their quantitative changes in pathological condition, their predictive value for the development of autoimmune condition and the staging process of certain diseases. MATERIALS AND METHODS:The study was conducted on a total of 41 patients exhibiting various underlying conditions generating immunosuppression: immunosuppressed (cirrhosis, diabetes, intubated, septicemia, LED, hepatitis, dialysis), rheumatic and emergency patients (patients with and without underlying conditions). For each patient the following parameters were determined: CRP, CIC, IgG, IgM, IgA serum complement and fibrinogen. We watched the variation of each parameter on patient groups and variation of each parameter within each group. RESULTS AND DISCUSSION:We noticed a clear correlation of elevated CRP in the group of rheumatic patients (100%), followed by immunocompromised patients (88%). Fibrinogen values were increased in rheumatic, sepsis and intubated patients and CIC levels in patients presented in emergency without underlying conditions, patients with cirrhosis and hepatitis and dialysis. All rheumatic patients had low C3 values. In terms of IgM, slightly higher values were found in the groups of patients with rheumatic disease and emergency patients,those with underlying conditions, obesity, dialysis, cirrhosis and hepatitis. IgM value was low in patients with osteoporosis. In the group of emergency patients without underlying conditions, CRP level was increased where an injury occurred, for example in patients with politraumatism, but the highest value of fibrinogen and CIC was observed in intoxicated patients, results that correlate with the fact that once formed the CIC can not be cleared from the body. In intoxicated patients C3 value correlated with high IgG value that may explain the phenomenon of cytolysis that accompanies this disease. High C3 value in patients with stroke and bleeding explain the action of anafilatoxins issued during complement system activation, functioning as potent mediators of inflammatory reactions. CONCLUSIONS:Biological markers used to assess autoimmune condition can provide useful information on physio-pathological mechanisms of self-aggression installation during various chronic or acute diseases. Analysis and correlation autoimmunity markers values in patients with acute or chronic pathologies demonstrated that immune imbalances are characteristic of a very broad spectrum of pathologies, which explains the 'iceberg' nature of poli-self-aggression, both in terms of etiology and large spectrum of clinical outcome of disease at individual and population level.
The interaction of C-reactive protein and serum amyloid P component with nuclear antigens.
Du Clos T W
Molecular biology reports
The pentraxins are a family of proteins characterized by cyclic pentameric structure, calcium-dependent ligand binding and sequence homology. The two main representatives of this family are the serum proteins, C-reactive protein (CRP) and serum amyloid P component (SAP). In man CRP is an acute phase reactant which increases up to 1,000 fold during the acute phase response whereas SAP is a constitutive protein expressed at about 30 micrograms/ml. These proteins activate complement through the classical pathway and participate in opsonization of particulate antigens and bacteria. In the past several years it has been determined that both of these pentraxins interact with nuclear antigens including chromatin and small nuclear ribonucleoproteins (snRNPs). Both CRP and SAP have nuclear transport signals which facilitate their entry into the nuclei of intact cells. Furthermore, these pentraxins have been shown to affect the clearance of nuclear antigens in vivo. It is now believed that one of the major functions of the pentraxins could be to interact with the nuclear antigens released from apoptotic or necrotic cells. This interaction could mitigate against deposition of these antigens in tissue and autoimmune reactivity.
10.1007/bf00351177
PTX3 Intercepts Vascular Inflammation in Systemic Immune-Mediated Diseases.
Ramirez Giuseppe A,Rovere-Querini Patrizia,Blasi Miriam,Sartorelli Silvia,Di Chio Maria Chiara,Baldini Mattia,De Lorenzo Rebecca,Bozzolo Enrica P,Leone Roberto,Mantovani Alberto,Manfredi Angelo A,Tombetti Enrico
Frontiers in immunology
PTX3 is a prototypic soluble pattern recognition receptor, expressed at sites of inflammation and involved in regulation of the tissue homeostasis. PTX3 systemic levels increase in many (but not all) immune-mediated inflammatory conditions. Research on PTX3 as a biomarker has so far focused on single diseases. Here, we performed a multi-group comparative study with the aim of identifying clinical and pathophysiological phenotypes associated with PTX3 release. PTX3 concentration was measured by ELISA in the plasma of 366 subjects, including 96 patients with giant cell arteritis (GCA), 42 with Takayasu's arteritis (TA), 10 with polymyalgia rheumatica (PMR), 63 with ANCA-associated systemic small vessel vasculitides (AAV), 55 with systemic lupus erythematosus (SLE), 21 with rheumatoid arthritis (RA) and 79 healthy controls (HC). Patients with SLE, AAV, TA and GCA, but not patients with RA and PMR, had higher PTX3 levels than HC. PTX3 concentration correlated with disease activity, acute phase reactants and prednisone dose. It was higher in females, in patients with recent-onset disease and in those with previous or current active vasculitis at univariate analysis. Active small- or large- vessel vasculitis were the main independent variables influencing PTX3 levels at multivariate analysis. High levels of PTX3 in the blood can contribute to identify an increased risk of vascular involvement in patients with systemic immune-mediated diseases.
10.3389/fimmu.2019.01135
Protective molecules--C-reactive protein (CRP), serum amyloid P (SAP), pentraxin3 (PTX3), mannose-binding lectin (MBL), and apolipoprotein A1 (Apo A1), and their autoantibodies: prevalence and clinical significance in autoimmunity.
Kravitz Martine Szyper,Pitashny Milena,Shoenfeld Yehuda
Journal of clinical immunology
Apoptotic defects and impaired clearance of cellular debris are considered key events in the development of autoimmunity, as they can contribute to autoantigen overload, and may initiate an autoimmune response. The pentraxins are a group of highly conserved proteins including the short pentraxins, C-reactive protein (CRP) and serum amyloid-P (SAP), and the long pentraxin-3 (PTX3), which are all involved in innate immunity and in acute-phase responses. Mannan-binding lectin (MBL) is an activator of the complement system, and Apolipoprotein A-1 (Apo A-1) is pivotal in the cholesterol homeostasis and has anti-inflammatory properties. In addition to their role in innate immunity and inflammation, each of these five proteins participates in the removal of damaged and apoptotic cells. In this review, we discuss the clinical significance of different levels of these proteins, their role in the induction or protection from autoimmunity, and the presence of specific autoantibodies against them in the different autoimmune diseases.
10.1007/s10875-005-7828-2
Long pentraxin 3 (PTX3) in the light of its structure, mechanism of action and clinical implications.
Cieślik Paweł,Hrycek Antoni
Autoimmunity
Pentraxins are a group of evolutionarily conserved ancient proteins. Depending on their structure, pentraxins are divided into short and long pentraxin families. Pentraxin 3 (PTX3) is the prototype of the long pentraxin group. PTX3 synthesis is stimulated by a variety of molecules involved in the inflammatory process. The inflammatory mediator is typically produced at inflammatory sites; however, it can also be released at the sites remote from the original inflammatory insult. Although mainly expressed by vascular endothelium and smooth muscle cells, PTX3 is also synthesized by myeloid dendritic cells, mononuclear macrophages/phagocytes, vascular endothelial and smooth muscle cells, fibroblasts, adipocytes, cumulus oophorus cells mesangial cells, synovial cells and chondrocytes. PTX3 binds to several ligands including complement component C1q, factor H, ficolin-1 (M-ficolin), mannose-binding lectin, fibroblast growth factor 2, P-selectin, matrix protein TSG6 and Klebsiella pneumoniae; it is also known to play a role in humoral innate immunity as well as in degenerated and apoptotic cells clearance. PTX3 acts as a modulator of inflammatory processes, modifies angiogenesis and atherosclerotic lesion development, and participates in extracellular matrix formation. Due to the fact of PTX3 being primarily produced and released by vascular wall cells, it might be used as a sensitive and independent inflammatory marker.
10.3109/08916934.2011.611549
Anti-Pentraxin Antibodies in Autoimmune Diseases: Bystanders or Pathophysiological Actors?
Brilland Benoit,Vinatier Emeline,Subra Jean-François,Jeannin Pascale,Augusto Jean-François,Delneste Yves
Frontiers in immunology
Pentraxins are soluble innate immunity receptors involved in sensing danger molecules. They are classified as short (CRP, SAP) and long pentraxin subfamilies, including the prototypic long pentraxin PTX3. Pentraxins act mainly as bridging molecules favoring the clearance of microbes and dead cells. They are also involved in many other biological processes, such as regulation of complement activation, inflammation and tissue homeostasis. Autoantibodies directed against pentraxins have been reported in various autoimmune diseases, especially in systemic lupus erythematosus and ANCA-associated vasculitis. In this review, we review the main biological characteristics and functions of pentraxins and summarize data concerning autoantibodies directed against pentraxins in the context of autoimmune diseases and discuss their potential pathological role.
10.3389/fimmu.2020.626343
Pattern recognition by pentraxins.
Agrawal Alok,Singh Prem Prakash,Bottazzi Barbara,Garlanda Cecilia,Mantovani Alberto
Advances in experimental medicine and biology
Pentraxins are a family of evolutionarily conserved pattern-recognition proteins that are made up of five identical subunits. Based on the primary structure of the subunit, the pentraxins are divided into two groups: short pentraxins and long pentraxins. C-reactive protein (CRP) and serum amyloid P-component (SAP) are the two short pentraxins. The prototype protein of the long pentraxin group is pentraxin 3 (PTX3). CRP and SAP are produced primarily in the liver while PTX3 is produced in a variety of tissues during inflammation. The main functions of short pentraxins are to recognize a variety of pathogenic agents and then to either eliminate them or neutralize their harmful effects by utilizing the complement pathways and macrophages in the host. CRP binds to modified low-density lipoproteins, bacterial polysaccharides, apoptotic cells, and nuclear materials. By virtue of these recognition functions, CRP participates in the resolution of cardiovascular, infectious, and autoimmune diseases. SAP recognizes carbohydrates, nuclear substances, and amyloid fibrils and thus participates in the resolution of infectious diseases, autoimmunity, and amyloidosis. PTX3 interacts with several ligands, including growth factors, extracellular matrix component and selected pathogens, playing a role in complement activation and facilitating pathogen recognition by phagocytes. In addition, data in gene-targeted mice show that PTX3 is essential in female fertility, participating in the assembly of the cumulus oophorus extracellular matrix. PTX3 is therefore a nonredundant component of the humoral arm of innate immunity as well as a tuner of inflammation. Thus, in conjunction with the other components of innate immunity, the pentraxins use their pattern-recognition property for the benefit of the host.
10.1007/978-1-4419-0901-5_7
Anti-pentraxin antibodies in autoimmune systemic diseases: Focus on anti-pentraxin-3 autoantibodies.
Augusto Jean-François,Poli Caroline,Beauvillain Céline,Subra Jean-François,Jaillon Sebastien,Renier Gilles,Chevailler Alain,Puéchal Xavier,Delneste Yves,Jeannin Pascale
International reviews of immunology
Pentraxins are soluble pattern recognition molecules implicated not only in the opsonization and removal of microorganisms but also in the clearance of modified self (i.e., dying cells). Pentraxins can be classified into short pentraxins (C-reactive protein and serum amyloid-P component) and long pentraxins with pentraxin-3 (PTX3), the prototypic one of the latter. Pentraxins are involved in various physiological or pathophysiological processes such as inflammation and autoimmunity. A breakdown in immune tolerance to pentraxins has been reported in various autoimmune diseases. In the present review, we analyzed the current knowledge concerning anti-pentraxin antibodies, with a special focus on anti-PTX3 autoantibodies.
10.1080/08830185.2017.1284210