Properdin

Envenomation by Loxosceles spiders can result in local and systemic pathologies. Systemic loxoscelism, which can lead to death, is characterized by intravascular hemolysis, platelet aggregation, and acute kidney injury. Sphingomyelinase D (SMase D) in Loxosceles spider venom is responsible for both local and systemic pathologies, and has been shown to induce metalloprotease activity. As the complement system is involved in many renal pathologies and is involved in hemolysis in systemic loxoscelism, the aim of this study was to investigate its role and the role of complement regulators and metalloproteases in an in vitro model of Loxosceles venom induced renal pathology...

Despite the progress of anti-cancer treatment, the prognosis of many patients with solid tumors is still dismal. Reliable noninvasive biomarkers are needed to predict patient survival and therapy response. Here, we propose a Humoral Complementomics approach: a work-up of assays to comprehensively evaluate complement proteins, activation fragments, and autoantibodies targeting complement proteins in plasma, which we correlated with the intratumoral complement activation, and/or local production, focusing on localized and metastatic clear cell renal cell carcinoma (ccRCC)...

INTRODUCTION: Disease subtyping and monitoring are essential for the management of nephrotic syndrome (NS). Although various biomarkers for NS have been reported, their clinical efficacy has not been comprehensively validated in adult Japanese patients. METHODS: The Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study is a nationwide, multicenter, and prospective cohort study in Japan, enrolling adult (≥18 years) patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), and lupus nephritis (LN)...

BACKGROUND: Emerging evidence has shown that myeloid cells that infiltrate into the peri-infarct region may influence the progression of ischemic stroke by interacting with microglia. Properdin, which is typically secreted by immune cells such as neutrophils, monocytes, and T cells, has been found to possess damage-associated molecular patterns (DAMPs) properties and can perform functions unrelated to the complement pathway. However, the role of properdin in modulating microglia-mediated post-stroke neuroinflammation remains unclear...

Schizophrenia has been linked to polymorphism in genes encoding components of the complement system, and hyperactive complement activity has been linked to immune dysfunction in schizophrenia patients. Whether and how specific complement components influence brain structure and cognition in the disease is unclear. Here we compared 52 drug-naïve patients with first-episode schizophrenia and 52 healthy controls in terms of levels of peripheral complement factors, cortical thickness (CT), logical memory and psychotic symptoms...

Activation of the alternative pathway (AP) of complement is involved in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), although the underlying molecular mechanisms are unclear. To gain insight into the role of the AP, common gene variants in CFH/CFHR1-5, CFB, C3 and MCP, and longitudinal determinations of plasma C3, C4, FH, FHR-1, FHR-2, FHR-5, FB, properdin and sC5b-9 levels were analyzed in a Spanish AAV cohort consisting of 102 patients; 54 with active AAV (active cohort) and 48 in remission not receiving immunosuppressants or dialysis therapy (remission cohort)...

BACKGROUND: Despite several advantages compared to haemodialysis (HD), peritoneal dialysis (PD) remains an underused dialysis technique due to its high technique failure rate related to membrane fibrosis and peritonitis events. Previous work has suggested a harmful role for the complement system in these processes, highlighting the need for a more comprehensive examination in PD. METHODS: Plasma levels of C1q, mannose-binding lectin (MBL), Properdin, Factor D, C3d/C3-ratio and soluble membrane attack complex (sC5b-9) were determined in PD patients ( n = 55), HD patients ( n = 41), non-dialysis chronic kidney disease (CKD) patients ( n = 15) and healthy controls ( n = 14)...

Cartilage acidic protein-1 (CRTAC1) is produced by several cell types, including Type 2 alveolar epithelial (T2AE) cells that are targeted by SARS-CoV2. Plasma CRTAC1 is known based on proteomic surveys to be low in patients with severe COVID-19. Using an ELISA, we found that patients treated for COVID-19 in an ICU almost uniformly had plasma concentrations of CRTAC1 below those of healthy controls. Magnitude of decrease in CRTAC1 distinguished COVID-19 from other causes of acute respiratory decompensation and correlated with established metrics of COVID-19 severity...

Hepatic ischemia/reperfusion injury (IRI) often causes serious complications in liver surgeries, including transplantation. Complement activation seems to be involved in hepatic IRI; however, no complement-targeted intervention has been clinically applied. We investigated the therapeutic potential of Properdin-targeted complement regulation in hepatic IRI. Male wild-type mice (B10D2/nSn) were exposed to 90-minute partial hepatic IRI to the left and median lobes with either monoclonal anti-Properdin-antibody (Ab) or control-immunoglobulin (IgG) administration...

INTRODUCTION: Upregulation of complement system factors are reported to be increased in polycystic ovary syndrome (PCOS) and may be due to obesity and insulin resistance rather than inherently due to PCOS. We directly compared complement factors from an obese, insulin-resistant PCOS population to a nonobese, non-insulin-resistant PCOS population in a proteomic analysis to investigate this. METHODS: Plasma was collected from 234 women (137 with PCOS and 97 controls) from a biobank cohort and compared to a nonobese, non-insulin-resistant population (24 with PCOS and 24 controls)...

BACKGROUND AND OBJECTIVE: Human plasma is used for the generation of several life-saving drugs and contains valuable antibodies from the immunoglobulin classes IgG, IgM and IgA. Purified intravenous IgG solutions (IVIGs) form the majority of plasma-derived medicine to treat patients with various forms of immunodeficiencies. In conventional IVIG manufacturing processes, immunoglobulin classes IgM and IgA are often discarded as contaminants, but these antibody classes have been proven to be effective for the treatment of acute bacterial infections...

[This corrects the article DOI: 10.3389/fimmu.2023.1183768.].

Proteinuria drives progressive tubulointerstitial fibrosis in native and transplanted kidneys, mainly through the activation of proximal tubular epithelial cells (PTECs). During proteinuria, PTEC syndecan-1 functions as a docking platform for properdin-mediated alternative complement activation. Non-viral gene delivery vectors to target PTEC syndecan-1 could be useful to slow down alternative complement activation. In this work, we characterize a PTEC-specific non-viral delivery vector composed of the cell-penetrating peptide crotamine complexed with a syndecan-1 targeting siRNA...

Phagocytosis plays vital roles in injury and repair, while its regulation by properdin and innate repair receptor, a heterodimer receptor of erythropoietin receptor (EPOR)/β common receptor (βcR), in renal ischaemia-reperfusion (IR) remains unclear. Properdin, a pattern recognition molecule, facilitates phagocytosis by opsonizing damaged cells. Our previous study showed that the phagocytic function of tubular epithelial cells isolated from properdin knockout ( PKO ) mouse kidneys was compromised, with upregulated EPOR in IR kidneys that was further raised by PKO at repair phase...

OBJECTIVE: Exacerbated inflammatory pathway has emerged as a predominant etiological construct of major depressive disorder (MDD). Innate immune molecules like complement proteins induce inflammatory responses and also regulate key neurobiological processes. However, there is a dearth of literature on the impact of critical complement proteins in MDD. Herein, plasma profiling of seven complement proteins was carried out to obtain a better insight into the role of the complement pathway in MDD...

OBJECTIVES: Pre-eclampsia (PE) is a leading cause of obstetric morbidity, with no definitive therapy other than delivery. We aimed to compare complement markers in maternal and fetal circulation, and placental tissue, between women with PE and healthy pregnant controls. STUDY DESIGN: Maternal and umbilical cord blood was tested for iC3b, C3, C4, properdin, Ba and C5b-9, and placental tissue for C3d, C4d, C9 and C1q, from women with PE (n = 34) and healthy pregnant controls (n = 33)...

BACKGROUND: Rates of Cannabis Use Disorder (CUD) are highest amongst young adults. Paucity of brain tissues samples limits the ability to examine the molecular basis of cannabis related neuropathology. Proteomic studies of neuron-derived extracellular vesicles (NDEs) isolated from the biofluids may reveal markers of neuropathology in CUD. METHODS: NDEs were extracted using ExoSORT, an immunoaffinity method to enrich NDEs from plasma samples from patients with young onset CUD and matched controls...

Complement is a major innate defense system that protects the intravascular space from microbial invasion. Complement activation results in the assembly of C3 convertases, serine proteases that cleave complement protein C3, generating bioactive fragments C3a and C3b. The complement response is rapid and robust, largely due to a positive feedback regulatory loop mediated by alternative pathway (AP) C3 convertase. C3 nephritic factors (C3NEFs) are autoantibodies that stabilize AP convertase, resulting in uncontrolled C3 cleavage, which, in principle, can promote critical tissue injury similar to that seen in certain renal conditions...

BACKGROUND: This study investigated the significance of galactose-deficient immunoglobulin A1 staining in kidney diseases with IgA deposition. METHODS: A total of 120 patients with IgA-dominant deposition in kidney tissues were enrolled and divided into four groups: primary IgA nephropathy (PIgAN), secondary IgA nephropathy (SIgAN), monotypic IgA nephropathy (MIgAN), and IgA variant monoclonal gammopathy of renal significance (IgA-MGRS). KM55 (the antibody of galactose-deficient immunoglobulin A1), IgA subtypes, and complement pathway factors (properdin, C4d, and C1q) were detected through immunofluorescence or immunohistochemistry analysis...

BACKGROUND: Anti-neutrophil cytoplasmic antibody vasculitis is characterized by antibodies to myeloperoxidase or proteinase 3. Previous work in murine anti-myeloperoxidase vasculitis has shown a role for the alternative pathway complement component factor B and the anaphylatoxin C5a. However, mice deficient in properdin, which stabilizes the alternative pathway convertase, were not protected. V-Type immunoglobulin domain-containing suppressor of T-cell activation (VISTA)-deficient mice were protected in the nephrotoxic nephritis model but the role of VISTA in anti-myeloperoxidase vasculitis is unknown...