Serum C1q Levels Research Articles

Ocular Tuberculosis Diagnosis Through Biomarkers: Clinical Relevance of Serum C1q and Whole Blood Interferon Gene Signature Score

ABSTRACT Purpose To assess the clinical relevance of pathophysiology-based biomarkers, specifically serum C1q and whole blood interferon gene signature score (IGSS), in ocular tuberculosis (OTB) diagnosis by conducting an integrative analysis of clinical presentations and treatment response. Methods This retrospective cohort study analysed data from 70 patients with suspected OTB at a tertiary care uveitis practice in Indonesia. Serum C1q levels and whole blood IGSS were quantified. Patients were categorized into four quadrants based on their biomarker profiles: quadrant 1 (high C1q & low IGSS), quadrant 2 (high C1q & high IGSS), quadrant 3 (low C1q & high IGSS), and quadrant 4 (low C1q & low IGSS). Characteristics of clinical presentations, work-up results, and treatment outcomes were explored according to the predefined quadrants. Results We identified that the majority of OTB patients diagnosed with concurrent active pulmonary TB were in quadrant 1, 2, or 3 (20/23, 87.0%). Twenty-seven patients (27/47, 57.4%) with clinically undifferentiated uveitis were in quadrant 4 (p < 0.001). Among patients in quadrants 1, 2, and 3, completion of a full course of antitubercular treatment (ATT) was associated with a lower number of patients showing persistence or recurrence of ocular inflammation compared to those who were not fully treated with ATT (14.3% vs 85.7%, p = 0.001). Conclusions Based on the analysis of clinical features and treatment outcomes, patients with elevated levels of either or both serum C1q and whole blood IGSS may reflect active TB disease in the eye, necessitating full ATT management.

Increasing serum complement component 1q is associated with worse prognosis in advanced non-small cell lung cancer treated with immune checkpoint inhibitors: a single-center, retrospective study.

There is a lack of readily available clinical markers of non-small cell lung cancer (NSCLC) immunotherapy efficacy. Previous studies have found that overexpressed complement component 1q (C1q) promotes macrophage M2 polarization and an immunosuppressive tumor microenvironment. This study aimed to evaluate the association between serum C1q and the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced NSCLC. A total of 168 patients with advanced NSCLC who received ICIs in the Renmin Hospital of Wuhan University were included in this study. Serum C1q levels were collected before and 3 weeks after immunotherapy treatment, together with other data on clinical and demographic characteristics. The primary outcome was overall survival (OS) (months from first dose of ICIs to death, censored at date of last follow-up). Secondary outcome was progression-free survival (PFS) [defined as months from first dose of ICIs to clinical or radiographic progression by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death, censored at date of last follow-up] and objective response rate (ORR) which was defined as rate of complete response (CR) or partial response (PR) at best response by RECIST 1.1. A total of 168 patients were included in this study, including 127 males (75.60%) and 41 females (24.40%). Thirty-nine patients achieved objective response (2 CR, 37 PR), and 111 patients (66.07%) had stable disease (SD) as best response. The ORR was 23.21% and the disease control rate was 89.28%. The upward trends of serum C1q levels between baseline and post-treatment were strongly associated with the shorter PFS [hazard ratio (HR) =1.554, 95% confidence interval (CI): 1.07-2.10, P=0.01] and OS (HR =1.444, 95% CI: 1.01-1.98, P=0.03). Moreover, taking the median OS 18.9 months as the cut-off of prognosis, receiver operating characteristic (ROC) analysis showed that serum baseline C1q yielded an area under the ROC curve of 0.785 (95% CI: 0.711-0.869). The optimal serum baseline C1q cut-off point to predict immunotherapy prognosis was 216.2 mg/L. These findings suggested that elevated serum C1q after ICIs treatment was related to a worse prognosis in NSCLC. Monitoring the baseline and dynamic data of C1q during hospitalization showed the potential to predict the prognosis of NSCLC patients.

Clinical value of serum complement component 1q levels in the prognostic analysis of aneurysmal subarachnoid hemorrhage: a prospective cohort study.

To analyze the relationship between serum complement component 1q (C1q) levels and functional prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH), and to reveal its clinical value. In this prospective cohort study, we collected clinical data of aSAH patients admitted to the Department of Neurosurgery, Hangzhou First People's Hospital from January 2020 to October 2022. Parameters such as serum C1q levels, Hunt-Hess grade, modified Fisher grade, and the modified Rankin scale (mRS) at 3 months were included for evaluation. Patients were grouped based on the occurrence of delayed cerebral ischemia (DCI). Spearman rank correlation test and Kruskal-Wallis rank sum test were used to analyze the correlation between serum C1q levels, disease severity, and prognosis. Potential risk factors affecting prognosis and the occurrence of DCI were screened through Independent sample t-test or Mann-Whitney U test. Variables with significant differences (p < 0.05) were incorporated into a logistic regression model to identify independent risk factors affecting prognosis and DCI occurrence. Serum C1q levels were plotted as a ROC curve for predicting prognosis and DCI, and the area under the curve was calculated. A total of 107 aSAH patients were analyzed. Serum C1q levels positively correlated with Hunt-Hess grade, modified Fisher grade and mRS (all p < 0.001). Significant differences were observed in C1q levels among different Hunt-Hess grade, mFisher grade and mRS (all p < 0.001). Notably, higher serum C1q levels were seen in the poor prognosis group and DCI group, and correlated with worse prognosis (OR = 36.927, 95%CI 2.003-680.711, p = 0.015), and an increased risk for DCI (OR = 17.334, 95%CI 1.161-258.859, p = 0.039). ROC analysis revealed the significant discriminative power of serum C1q levels for poor prognosis (AUC 0.781; 95%CI 0.673-0.888; p < 0.001) and DCI occurrence (AUC 0.763; 95%CI 0.637-0.888; p < 0.001). Higher C1q levels independently predicted a poor prognosis and DCI with equivalent predictive abilities to Hunt-Hess grade and modified Fisher grade (both p < 0.05). High levels of C1q in the blood is an independent risk factor for poor prognosis and the development of DCI in patients with aSAH. This can more objectively and accurately predict functional outcomes and the incidence of DCI. C1q may have a significant role in the mechanism behind DCI after aSAH.

Diagnostic and Prognostic Value of C1q in Sepsis-Induced Coagulopathy.

Early identification of biomarkers that can predict the onset of sepsis-induced coagulopathy (SIC) in septic patients is clinically important. This study endeavors to examine the diagnostic and prognostic utility of serum C1q in the context of SIC. Clinical data from 279 patients diagnosed with sepsis at the Departments of Intensive Care, Respiratory Intensive Care, and Infectious Diseases at the Renmin Hospital of Wuhan University were gathered spanning from January 2022 to January 2024. These patients were categorized into two groups: the SIC group comprising 108 cases and the non-SIC group consisting of 171 cases, based on the presence of SIC. Within the SIC group, patients were further subdivided into a survival group (43 cases) and non-survival group (65 cases). The concentration of serum C1q in the SIC group was significantly lower than that in the non-SIC group. Furthermore, A significant correlation was observed between serum C1q levels and both SIC score and coagulation indices. C1q demonstrated superior diagnostic and prognostic performance for SIC patients, as indicated by a higher area under the curve (AUC). Notably, when combined with CRP, PCT, and SOFA score, C1q displayed the most robust diagnostic efficacy for SIC. Moreover, the combination of C1q with the SOFA score heightened predictive value concerning the 28-day mortality of SIC patients.

Identification of circulating monocytes as producers of tuberculosis disease biomarker C1q

Tuberculosis (TB) is a prevalent disease causing an estimated 1.6 million deaths and 10.6 million new cases annually. Discriminating TB disease from differential diagnoses can be complex, particularly in the field. Increased levels of complement component C1q in serum have been identified as a specific and accessible biomarker for TB disease but the source of C1q in circulation has not been identified. Here, data and samples previously collected from human cohorts, a clinical trial and a non-human primate study were used to identify cells producing C1q in circulation. Cell subset frequencies were correlated with serum C1q levels and combined with single cell RNA sequencing and flow cytometry analyses. This identified monocytes as C1q producers in circulation, with a pronounced expression of C1q in classical and intermediate monocytes and variable expression in non-classical monocytes.

Association between serum baseline C1q and IgG levels and the efficacy of combined immunotherapy in patients with esophageal squamous cell carcinoma: a retrospective study

Background To assess the clinical value of serum complement component 1q (C1q) and immunoglobulin G (IgG) levels in predicting the response to combined immunotherapy in patients with esophageal squamous cell carcinoma. Methods We conducted a retrospective study of 44 patients with esophageal squamous cell carcinoma who received combined immunotherapy in our hospital. Serum IgG and C1q levels were collected before and three weeks after immunotherapy treatment, together with other data on clinical and demographic characteristics. Results Twenty seven patients (61.4%) showed partial response (PR), 13 (29.5%) stable disease (SD), and 4 (9.1%) progressive disease (PD). None of the patients presented complete response (CR). The PR group displayed lower IgG and higher C1q levels both before and after immunotherapy than patients showing SD or PD. The IgG reduction (59.3%) and C1q increment (70.3%) in the PR group three weeks post-treatment were significantly larger than those in patients showing SD or PD. Moreover, the pretreatment C1q level and the post-treatment change of C1q levels were strongly associated with the immunotherapy response. Conclusions High pre- and post-treatment C1q levels and reduced post-treatment IgG levels correlate with efficacy of combined immunotherapy in patients with esophageal squamous cell carcinoma. Serum baseline C1q level may predict immunotherapy response in such patients.

Complement complex 1 subunit q-mediated hepatic stellate cell activation with connective tissue growth factor elevation is a prognostic factor for survival in rat and human chronic liver diseases.

Complement complex 1 subunit q (C1q) has multiple functions, including cell migration, in addition to its traditional complement-activating effect. Research shows C1q is a ligand for frizzled receptors (FZDs). FZD-induced yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) alternate Wnt signaling activation induces connective tissue growth factor (CTGF) production and hepatic stellate cell (HSC) activation. However, no study exists in which C1q directly induces CTGF in HSCs. Here, we investigated the role of C1q in HSC activation. Human HSCs (LX2) were incubated with C1q to assess HSC activation. C1q and fibrotic markers were assessed using immunohistochemistry, immunoblotting, and quantitative reverse-transcription polymerase chain reaction in cirrhotic rats administered CCl4 for 21 weeks. Serum C1q, liver function, and fibrosis score were measured in 91 patients with chronic liver disease. The correlations between serum C1q and liver function, fibrosis score, and survival prognosis were examined. C1q-activated LX2s showed morphologic changes, up-regulation of CTGF, tissue inhibitors of metalloproteinases (TIMP-1),and alternate Wnt signal genes FZD2, TAZ, and cysteine-rich angiogenic inducer 61 (Cyr61). Cirrhotic rat liver C1q expression correlated with the Azan-positive area and expression of CTGF, TIMP-1, hyaluronan synthase (HAS)1, HAS3, and CD44. Expression of C1q protein and C1q, CTGF, and TIMP-1 genes were higher in deceased cirrhotic rat livers compared to surviving rats. Human serum C1q levels increased in liver cirrhosis compared to chronic hepatitis and correlated with liver fibrosis and functional markers. Ten patients suffered liver-related death over a 66-month observation period. The C1q cut-off value (11 mg/dl) showed patients with serum values < 11 mg/dl had longer rates of survival compared to C1q ≥ 11 mg/dl. Conclusion: C1q-mediated HSC activation in liver fibrosis is associated with CTGF elevation. Additionally, serum C1q may be diagnostic for survival in human chronic liver diseases.

The differences in serum C1q levels between first-episode patients with bipolar disorder and major depressive disorder

ObjectiveThis study aimed at exploring the changes of serum complement C1q levels in patients with Bipolar Disorder (BD) using a cross-sectional design, and the differences between Major Depressive Disorder (MDD) and BD. Moreover, the correlation between complement C1q and bech-rafaelsdn mania rating scales (BRMS) in patients with MDD and BD was assessed. MethodsSerum complement C1q levels were measured by ADVIA 2400 biochemical analyser in 104 patients with MDD, 71 patients with BD type I and 42 patients with BD type II diagnosed by Diagnostic and Statistical of Mental Disorder 5 (DSM-5). Then simple and multivariate linear regression analysis was conducted between the level of serum C1q and BRMS among patients with BD. ResultsThe serum complement C1q levels were higher in BD type I than BD type II (P < 0.001); Serum complement C1q levels were higher in MDD than BD type II (P < 0.001). We discovered that there was a positive correlation relationship between serum complement C1q levels and BRMS in BD type I (r = 0.756, P < 0.001). ConclusionWe confirmed that serum complement C1q levels were higher in patients with BD type II than in MDD patients. These current results support the view that the complement C1q may play an important role in the pathophysiology of BD. Serum complement C1q was strongly associated with BD and is worth investigating in future studies.

Abnormal lower expression of GPR183 in peripheral blood T and B cell subsets of systemic lupus erythematosus patients

G protein-coupled receptor 183 (GPR183) has been indicated to mediate the migration and localisation of immune cells in T cell-dependent antibody responses. Systemic lupus erythematosus (SLE) is a canonical autoimmune disease involving B cell-mediated tolerance destruction and excessive pathogenic autoantibody production, in which multiple GPCRs play a role. To date, there has been no systematic study regarding the expression of GPR183 in lymphocyte subsets of SLE patients. In this research, firstly, we observed the expression trends of GRP183 in various T and B cell subsets in human tonsil tissues. These lymphocyte subsets include CD4+, CD8+, naïve T, effector T, Tfh, activated Tfh, Th1, Th2, Th17, Treg, CD19+CD27-, CD19+CD27+, naïve B, germinal centre B, memory B, and plasma cells. Further, compared with healthy controls (HCs), GPR183 expression levels in above peripheral blood lymphocyte subsets of patients with SLE were reduced overall. The differential expression of GPR183 expression between inactive and active SLE patients indicates that GPR183 expression may be concerned with the disease activity of SLE. This was further confirmed through the strong negative correlation with SLEDAI score and positive correlation with serum complement protein C3, C4 and C1q levels. Further receiver operating characteristic (ROC) curve analysis revealed that GPR183 expression in circulating CD27-IgD+ B cells may be beneficial in distinguishing between inactive and active SLE patients. In addition, type I interferon stimulation could down-regulate the expression of GPR183 in peripheral blood T and B cell subsets. Aberrant expression of GPR183 may provide some novel insights into disease activity prediction and underlying pathogenesis of SLE.

Circulating Complement C1q as a Novel Biomarker is Associated with the Occurrence and Development of COPD.

PurposeIncreasing evidence has shown that the immune response interacts with the chronic inflammatory response and gives rise to the occurrence and development of COPD. Complement component 1q (C1q), as a subcomponent of the C1 complex, could be involved in innate and adaptive immunity. Our study aimed to investigate the relationship between C1q and the clinical characteristics of COPD subjects.Patients and MethodsSerum C1q levels were measured in 203 COPD subjects and 191 non-COPD controls. Correlations between C1q and the characteristics of COPD were analyzed using Spearman’s rho. Receiver operating curve (ROC) analysis was used to evaluate the threshold value in differentiating disease status. All 203 COPD subjects were followed up for 1 year for future acute exacerbations.ResultsThere were significant reductions in serum C1q levels in COPD subjects compared to non-COPD controls. Moreover, serum C1q levels were obviously positively correlated with the FEV1/FVC ratio and predicted FEV1% but had a weakly negative correlation with the %LAA-950 and the percentage of neutrophils in peripheral blood. Using a cutoff value of 137.150 mg/l as the boundary in ROC analysis, the sensitivity and specificity were 65.9% and 76.0%, respectively. The 1-year follow-up results showed that C1q levels less than 137.150 mg/l were negatively related to the time to the next severe exacerbation and the time to death.ConclusionCirculating C1q levels may be a novel biomarker not only related to the pulmonary function of COPD but also having great potential to predict the risk of COPD deterioration in the future. However, further prospective trials are needed to clarify the influences of C1q on the pathogenesis of COPD.

Elevated Serum Complement C1q Levels After Traumatic Brain Injury and Its Association with Poor Prognosis.

ObjectiveComplement C1q is implicated in neuroinflammation. We intended to discern the relationship between serum C1q levels and severity in addition to prognosis following traumatic brain injury (TBI).MethodsIn this prospective, observational study, serum C1q levels were quantified in 188 TBI patients and 188 healthy controls. Glasgow coma scale (GCS) and Rotterdam computed tomography (CT) classification were used as clinical and radiological indicators of severity. Patients with extended Glasgow outcome scale (GOSE) score of 1–4 at 6 months after trauma were considered to have a poor outcome. Multiple logistic regression model was built to ascertain the independent association of serum C1q levels with 6-month poor outcome. Receiver operating characteristic (ROC) curve was configured for analysis of prognostic capability with respect to serum C1q levels.ResultsTBI patients exhibited substantially higher serum C1q levels than controls (median, 223.9 mg/l versus 75.4 mg/l). Serum C1q levels of patients were tightly correlated with GCS score (r = −0.671), Rotterdam CT classification (r = 0.604) and GOSE score (r = −0.581). An area under the ROC curve was yielded of 0.793 (95% confidence interval = 0.728–0.849), and serum C1q levels above 345.5 mg/l discriminated the risk of 6-month poor outcome with 59.6% sensitivity and 92.6% specificity. Serum C1q levels above 345.5 mg/l retained as an independent predictor for 6-month poor outcome with odds ratio of 4.922 (95% confidence interval = 1.552–15.606; P = 0.017).ConclusionElevated serum C1q levels are closely correlated with traumatic severity and independently predicted the risk of long-term poor prognosis after TBI.

C1q inhibits differentiation of oligodendrocyte progenitor cells via Wnt/β-catenin signaling activation in a cuprizone-induced mouse model of multiple sclerosis

Multiple sclerosis (MS) is a chronic central nervous system demyelinating disease of autoimmune originate. Complement C1q, a complex glycoprotein, mediates a variety of immunoregulatory functions considered important in the prevention of autoimmunity. Although we found that the increased serum C1q level was highly associated with the Fazekas scores and T2 lesion volume of MS patients, the effect and mechanism of C1q on demyelination remains unclear. Cluster analysis and protein array results showed that serum Wnt receptors Frizzled-6 and LRP-6 levels in MS patients were both increased, we proposed that C1q may be involved in demyelination via Wnt signaling. The increased C1q protein levels in the serum and brain tissue were confirmed in a cuprizone (CPZ)-induced demyelination mice model. Moreover, CPZ treatment induced significant increase of LRP-6 and Frizzled-6 protein in mice corpus callosum. LRP-6 extra-cellular domain (LRP-6-ECD) level in the serum and cerebrospinal fluid (CSF) of CPZ mice also significantly increased. Knockdown of the subunit C1s of C1 not only substantially attenuated demyelination, promoted M2 microglia polarization and improved neurological function, but inhibited β-catenin expression and its nuclear translocation in oligodendrocyte progenitor cells (OPCs). In vitro, C1s silence reversed the increased level of LRP-6-ECD in the medium and β-catenin expression in OPCs induced by C1q treatment. Meanwhile, inhibition of C1s also markedly lowered the number of EDU positive OPCs, but enhanced the number of CNPase positive oligodendrocyte and the protein of MBP. The present study indicated that C1q was involved in demyelination in response to CPZ in mice by preventing OPC from differentiating into mature oligodendrocyte via Wnt/β-catenin signaling activation.

Serum Level of Complement C1q is Associated with Contrast-Associated Acute Kidney Injury in Patients Undergoing Emergency Percutaneous Coronary Intervention.

BackgroundAs an inflammatory factor, complement C1q is related to the prevalence and progression of atherosclerosis; however, in patients undergoing emergency percutaneous coronary intervention (PCI), it is unclear whether C1q is related to the prevalence of contrast-associated acute kidney injury (CA-AKI).MethodsFrom November 2018 to March 2021, 1182 patients who underwent emergency PCI were continuously recruited. Patients were divided into CA-AKI group (n = 234) and non-CA-AKI group (n = 948). CA-AKI was defined as an increase in serum creatinine from the baseline level (≥25% or ≥0.5 mg/dL) 48–72 hours after contrast exposure. All subjects were tested for serum C1q levels when they were admitted to the hospital.ResultsAmong the 1182 patients undergoing emergency PCI, 234 patients (19.80%) developed CA-AKI. The level of preoperative serum complement C1q in the CA-AKI group was significantly higher than that in the non-CA-AKI group. Logistic regression and restricted cubic spline analyses showed that the incidence of CA-AKI was positively associated with the serum C1q level pre-PCI. Univariate and multivariate logistic regression analyses showed that C1q was an independent predictor of whether CA-AKI occurred after emergency PCI. The area under the curve (AUC) of the C1q was 0.703 [95% confidence interval (CI) 0.667–0.739] in patients receiving emergency PCI. CA-AKI model included the following three predictors: C1q, eGFR, and IABP use. The AUC of forecast probability was 0.718 [95% CI 0.682–0.754].ConclusionIn patients receiving emergency PCI procedure, a high C1q level before PCI is associated with the increased risk of CA-AKI.

A Preliminary Study of the Complement Component 1q Levels in Predicting the Efficacy of Combined Immunotherapy in Patients with Lung Cancer.

ObjectiveTo evaluate the value of serum complement component 1q (C1q) levels in predicting the efficacy of combined immunotherapy in patients with lung cancer.MethodsA total of 42 patients with lung cancer who received combined immunotherapy in the cancer center of Renmin Hospital of Wuhan University were included in this study. The clinical data of serum C1q and lactate dehydrogenase (LDH) levels before and three weeks after immunotherapy were collected.ResultsResponse evaluation showed that the number of patients with complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) was 0 (0%), 26 (61.9%), 14 (33.3%), and 2 (4.8%), respectively. The CR/PR group (patients with CR or PR) showed higher pC1q (C1q level before immunotherapy) and iC1q (C1q level 3 weeks after immunotherapy) than the SD/PD group (patients with SD or PD). The LDH reduction (96.2%) and C1q increment (84.6%) in the CR/PR group 3 weeks after immunotherapy were higher than those of the SD/PD group, and the differences were statistically significant. Logistic regression analysis indicated that pC1q, iC1q, and LDH level trends 3 weeks after the treatment were significantly correlated to the efficacy of combined immunotherapy with odds ratios of 8.185, 5.500, and 0.031, respectively.ConclusionHigh C1q levels before immunotherapy and increased C1q levels and decreased LDH levels 3 weeks afterward suggest good therapeutic effects of combined immunotherapy in patients with lung cancer. Serum C1q levels have certain clinical significance in predicting the efficacy of combined immunotherapy.

Serum C1q Levels Have Prognostic Value for Sepsis and are Related to the Severity of Sepsis and Organ Damage.

ObjectiveTo explore the clinical application value of serum complement component C1q levels in sepsis.MethodsThe clinical data and laboratory examination data of 320 research subjects (including 132 cases as sepsis group, 93 cases as nonsepsis group and 95 cases as control group) who were diagnosed and treated in Renmin Hospital of Wuhan University from July 2020 to March 2021 were collected. We compared the levels of each index among the three groups and further analyzed the C1q levels of different severity subgroups and different outcome subgroups of sepsis. Afterwards, we explored the correlation between C1q levels and SOFA score, organ damage indexes and coagulation indexes. Finally, the receiver operating characteristic curve (ROC) was used to analyze the prognostic value of C1q in patients with sepsis.ResultsC1q levels were significantly reduced in the serum of patients with sepsis; the level of C1q in the death group was lower than that in the survival group (127.1 mg/L vs 153.2 mg/L, P < 0.05), and the mortality in the C1q decreased group was higher when compared with C1q normal group; in addition, serum C1q levels were correlated with SOFA score, organ damage indexes and coagulation indexes; C1q had a high area under the curve (AUC) for the prognosis of sepsis, and the combination of other indexes can further improve the prognostic value.ConclusionSerum C1q levels have potential clinical value for the condition and prognosis of sepsis.

Novel Monoclonal Antibodies Against Mouse C1q: Characterisation and Development of a Quantitative ELISA for Mouse C1q

Recent studies have identified roles for complement in synaptic pruning, both physiological during development and pathological in Alzheimer’s disease (AD). These reports suggest that C1q initiates complement activation on synapses and C3 fragments then tag them for removal by microglia. There is an urgent need to characterise these processes in rodent AD models; this requires the development of reagents and methods for detection and quantification of rodent C1q in fluids and pathological tissues. These will enable better evaluation of the role of C1q in disease and its value as disease biomarker. We describe the generation in C1q-deficient mice of novel monoclonal antibodies against mouse and rat C1q that enabled development of a sensitive, specific, and quantitative ELISA for mouse and rat C1q capable of measuring C1q in biological fluids and tissue extracts. Serum C1q levels were measured in wild-type (WT), C1q knockout (KO), C3 KO, C7 KO, Crry KO, and 3xTg and APPNL-G-F AD model mice through ageing. C1q levels significantly decreased in WT, APPNL-G-F, and C7 KO mice with ageing. C1q levels were reduced in APPNL-G-F compared to WT at all ages and in 3xTg at 12 months; C3 KO and C7 KO, but not Crry KO mice, also demonstrated significantly lower C1q levels compared to matched WT. In brain homogenates, C1q levels increased with age in both WT and APPNL-G-F mice. This robust and adaptable assay for quantification of mouse and rat C1q provides a vital tool for investigating the expression of C1q in rodent models of AD and other complement-driven pathologies.

Serum Complement C1q Activity Is Associated With Obstructive Coronary Artery Disease.

Background: Complement C1q plays a dual role in the atherosclerosis. Previous studies showed inconsistent results about the association of serum C1q levels and coronary artery disease (CAD). Here, we explored the associations of serum C1q activity with CAD, coronary stenosis severity, cardiovascular biomarkers, and 1-year restenosis after coronary artery revascularization.Methods: We enrolled 956 CAD patients and 677 controls to evaluate the associations of serum complement C1q activity to the presence and severity of obstructive CAD and non-obstructive CAD. Serum C1q activity and the concentrations of laboratory markers were measured in all subjects. All the data were analyzed using SPSS22.0 software.Results: Serum C1q activity in Obstructive CAD and Non-Obstructive CAD groups was significantly higher than the control group (195.52 ± 48.31 kU/L and 195.42 ± 51.25 kU/L vs. 183.44 ± 31.75 kU/L, P < 0.05). Greater C1q activity was significantly correlated with higher total cholesterol (TC) and triglyceride (TG) levels. C1q activity was associated with an increased Odds Ratio (OR) of CAD (OR = 1.322, 95% CI 1.168–1.496, P < 0.05) and 1-year restenosis after revascularization (the highest OR = 3.544, 95% CI 1.089–12.702, P < 0.05). Complement C1q activity was not correlated with Gensini score in the Obstructive CAD group after adjustment for confounders. C1q activity has low value in predicting the incidence of CAD.Conclusion: Serum complement C1q activity is associated with obstructive CAD.

Elevated Serum C1q Levels in Children With Sepsis.

Objective: To analyze the serum complement C1q levels in children with sepsis, and explore the suggestive effect of serum C1q levels on the condition of children with sepsis.Methods: The clinical and laboratory data of children with sepsis (n = 95) and healthy children (n = 71) in Renmin Hospital of Wuhan University from January 2019 to October 2019 were collected, and each index of the two groups was compared. Then we divided children with sepsis into three subgroups based on the Pediatric Critical Illness Score (PCIS): non-critical group, critical group, and extremely critical group. The serum C1q and PCT levels of the three subgroups were analyzed, and the correlation analysis was carried out between the levels of serum C1q and PCT levels as well as PCIS among children with sepsis. Finally, we analyzed the serum C1q levels of septic children infected by different pathogens.Results: The serum C1q levels of children with sepsis were significantly higher than those of healthy children (median 198.4 vs. 186.2 mg/L, P < 0.001). In the analysis of subgroups, the serum C1q levels of non-critical group, critical group, and extremely critical group septic children were 182.80 (166.75, 195.85) mg/L, 219.90 (209.10, 246.40) mg/L and 249.95 (239.10, 272.25) mg/L, respectively, which were correlated with the severity of the disease. At the same time, we also found that serum C1q in children with sepsis was positively correlated with PCT levels (r = 0.5982, P < 0.001), and negatively correlated with PCIS score (r = −0.6607, P < 0.001). The serum C1q levels of septic children with bacterial infections, mycoplasma infections, viral infections, and co-infection were higher than those of the control group (P < 0.05).Conclusion: The serum levels of C1q in children with sepsis were increased and related to the severity of sepsis, suggesting that C1q may be involved in the occurrence and development of sepsis, which had reference value for the preliminary diagnosis and severity classification of sepsis.

Serum C1q concentration is associated with disease activity in Chinese Takayasu arteritis patients: A case-control study.

BackgroundC1q is a crucial component of the classical complement pathway. This study is the first to assess the association between disease activity and serum levels of C1q in Chinese Takayasu arteritis (TA) patients.MethodsSerum C1q levels in 198 TA patients and 154 healthy controls were assessed, and the relationship between serum C1q levels and indices of TA disease activity was analyzed. Moreover, we examined the correlation between serum C1q levels and two traditional inflammatory biomarkers; erythrocyte sedimentation rate (ESR) and hypersensitive CRP (hs‐CRP).ResultsSerum C1q levels were increased in TA patients compared with healthy controls (P = .008). TA patients with active disease had higher levels of serum C1q than patients who had inactive disease (P < .0001). In addition, treatment‐naïve patients had higher serum C1q levels than those who had been treated with corticosteroids or at least one immunosuppressant (P = .001). Furthermore, a positive correlation between serum C1q levels and traditional inflammatory biomarkers in TA patients was found. The role of C1q in assessing disease activity was studied, and the area under the receiver operating characteristic curve (AUC) of C1q for predicting active disease was 0.752, and a serum cutoff value of 167.15 mg/L C1q maximized the ability of disease activity assessment, with a sensitivity/specificity of 77.80%/64.90%. When the three indicators (C1q, ESR, and hs‐CRP) were combined, the AUC increased to 0.845, and the sensitivity to 84.40%.ConclusionsThe serum C1q is associated with the disease activity of TA and the combination of three indicators (C1q, ESR, and hs‐CRP) increases the sensitivity of disease activity assessment.

Association of Serum Complement C1q Concentration with Severity of Neurological Impairment and Infarct size in Patients with Acute Ischemic Stroke

Inflammation occurs after acute ischemic stroke (AIS), and complement C1q is involved in inflammation. However, studies about the association of complement C1q with AIS are still rare. The aim of our study is to investigate the relationship between serum C1q concentration and the clinical severity of AIS. A total of 1294 patients were enrolled in our study, including 647 patients with AIS and 647 non-stroke controls. The infarction volume of AIS was assessed by the diameter of maximum transverse section (DMTS) based on diffusion-weighted imaging (DWI) of brain magnetic resonance imaging. Neurological impairment was assessed by the National Institute of Health Stroke Scale (NIHSS). The association of serum C1q levels with DMTS or NIHSS was investigated by Pearson's or Spearman's correlation analysis. Serum C1q levels of patients with AIS were significantly higher than those of individuals without AIS. Serum levels of C1q were associated with DMTS (r=0.511, p<0.001) and NIHSS (r=0.433, p<0.001) among patients with AIS. Serum C1q concentration was positively associated with DMTS and NIHSS of patients with AIS.