C1q Levels Research Articles

Effect of electroacupuncture on complement C1q and microglia phagocytosis in hippocampus of SAMP8 mice

To observe the effect of electroacupuncture (EA) on the expression of Iba-1, complement C1q and CD68 in hippocampus of SAMP8 mice, so as to explore its mechanisms underlying improvement of Alzheimer's disease (AD). Twenty-four male SAMP8 mice were randomly and equally divided into model and EA groups, and 12 SAMR1 mice were used as the control group. EA (2 Hz, 1.5-2.0 mA) was applied to "Baihui" (GV20), "Dazhui"(GV14) and "Shen-shu"(BL23) for 20 min once daily in the EA group, each course of treatment was 8 days, with an interval of 2 days between two courses, and the mice were treated for 3 courses. Morris water maze test was performed to assess the learning-memory ability of mice. The positive expression levels of Iba-1 and CD68 proteins in the hippocampus CA1 region were detected by immunohistochemistry. The mRNA and protein expression levels of Iba-1,C1q and CD68 in the hippocampus were detected by real-time PCR and Western blot, separately. Compared with the control group, the average escape latency of Morris water maze test was prolonged in the model group (P<0.01), duration of swimming in the original platform quadrant and the number of original platform crossing were significantly shorter and decreased respectively (P<0.01). Compared with the model group, the average escape latency in the EA group was shortened (P<0.05, P<0.01), the duration of swimming in the original platform quadrant and the number of original platform crossing were significantly prolonged and increased (P<0.01). The immunoactivity of Iba-1 and CD68 in hippocampal CA1 region, and mRNA and protein expression levels of hippocampal Iba-1,C1q and CD68 were significantly up-regulated in the model group in contrast to the control group (P<0.01, P<0.05), and obviously down-regulated except the mRNA expression level of hippocampal Iba-1 in the EA group relevant to the model group (P<0.01, P<0.05). EA can improve the learning and memory ability of SAMP8 mice, which may be associated with its effect in inhibiting of complement C1q-dependent microglial phagocytosis in the hippocampus.

Elevated Plasma Complement C1q Levels Contribute to a Poor Prognosis After Acute Primary Intracerebral Hemorrhage: A Prospective Cohort Study.

ObjectiveThe complement cascade is activated early following intracerebral hemorrhage (ICH) and causes acute brain injury. We intended to explore the effects of plasma complement component 1q (C1q) levels on hemorrhagic severity and functional outcome in ICH patients.MethodsIn this prospective cohort study, we measured the plasma C1q levels of 101 ICH patients and 101 healthy controls. The Glasgow Coma Scale (GCS) score and hematoma volume were used to assess the ICH severity. Poor prognosis was referred to as a Glasgow Outcome Scale (GOS) score of 1-3 at three months following a stroke. A multivariate logistic regression model was configured to determine the independent relation of plasma C1q levels to severity and poor prognosis. Under receiver operating characteristic (ROC) curve, prognostic capability of plasma C1q levels was evaluated.ResultsThere was a significant elevation of plasma C1q levels in patients, as compared to controls [median (percentiles 25th-75th), 225.04 mg/l (156.10-280.15 mg/l) versus 88.18 mg/l (70.12-117.69 mg/l); P<0.001]. Plasma C1q levels of patients were independently related to GCS score (t =-3.281, P=0.001) and hematoma volume (t = 2.401, P=0.018), and were highly correlated with the GOS score at 3 months post-stroke (r=-0.658, P<0.001). Plasma C1q levels were obviously higher in poor prognosis patients than in other remainders (median percentiles 25th-75th), 278.40 mg/l (213.81-340.05 mg/l) versus 174.69 mg/l (141.21-239.93 mg/l); P<0.001). Under the ROC curve, plasma C1q levels significantly discriminated the development of poor prognosis (area under ROC curve 0.795; 95% confidence interval, 0.703–0.869; P<0.001). Using maximum Youden method, plasma C1q levels > 270.11 mg/l distinguished patients at risk of poor prognosis at 3 months with 56.52% sensitivity and 94.55% specificity. Meanwhile, the prognostic predictive ability of plasma C1q levels was equivalent to those of GCS score and hematoma volume (both P>0.05). Moreover, plasma C1q levels > 270.11 mg/l independently predicted a poor prognosis at 3 months (odds ratio, 4.821; 95% confidence interval, 1.211-19.200; P=0.026).ConclusionPlasma C1q levels are closely related to the illness severity and poor prognosis of ICH at 3 months. Hence, complement C1q may play an important role in acute brain injury after ICH and plasma C1q may represent a promising prognostic predictor of ICH.

Variation of Complement Protein Levels in Maternal Plasma and Umbilical Cord Blood during Normal Pregnancy: An Observational Study.

The complement system constitutes a crucial part of the innate immunity, mediating opsonization, lysis, inflammation, and elimination of potential pathogens. In general, there is an increased activity of the complement system during pregnancy, which is essential for maintaining the host’s defense and fetal survival. Unbalanced or excessive activation of the complement system in the placenta is associated with pregnancy complications, such as miscarriage, preeclampsia, and premature birth. Nonetheless, the actual clinical value of monitoring the activation of the complement system during pregnancy remains to be investigated. Unfortunately, normal reference values specifically for pregnant women are missing, and for umbilical cord blood (UCB), data on complement protein levels are scarce. Herein, complement protein analyses (C1q, C3, C4, C3d levels, and C3d/C3 ratio) were performed in plasma samples from 100 healthy, non-medicated and non-smoking pregnant women, collected during different trimesters and at the time of delivery. In addition, UCB was collected at all deliveries. Maternal plasma C1q and C3d/C3 ratio showed the highest mean values during the first trimester, whereas C3, C4, and C3d had rising values until delivery. We observed low levels of C1q and C4 as well as increased C3d and C3d/C3 ratio, particularly during the first trimester, as a sign of complement activation in some women. However, the reference limits of complement analyses applied for the general population appeared appropriate for the majority of the samples. As expected, the mean complement concentrations in UCB were much lower than in maternal plasma, due to the immature complement system in neonates.

Single-cell RNA sequencing reveals immunological rewiring at the maternal-fetal interface following asymptomatic/mild SARS-CoV-2 infection.

While severe coronavirus 2019 (COVID-19) is associated with immune activation at the maternal-fetal interface, responses to asymptomatic/mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain unknown. Here, we assess immunological adaptations in blood and term decidua in response to asymptomatic/mild disease in pregnant women. We report attenuated antigen presentation and type I interferon (IFN) signaling pathways, loss of tissue-resident decidual macrophages, and upregulated cytokine/chemokine signaling in monocyte-derived decidual macrophages. Furthermore, we describe increased frequencies of activated tissue-resident T cells and decreased abundance of regulatory T cells with infection while frequencies of cytotoxic CD4/CD8 T cells are increased in the blood. In contrast to decidual macrophages, type I IFN signaling is higher in decidual T cells. Finally, infection leads to a narrowing of T cell receptor diversity in both blood and decidua. Collectively, these observations indicate that asymptomatic/mild COVID-19 during pregnancy results in remodeling of the immunological landscape of the maternal-fetal interface, with a potential for long-term adverse outcomes for the offspring.

Changes of Serum Complement C1q in Patients with Multiple Myeloma

To analyze the change of serum C1q in the course of multiple myeloma (MM) and its correlation with clinical characteristics. A total of 138 newly diagnosed MM patients in Zhongnan Hospital of Wuhan University from June 2016 to December 2019 were selected as research objects, during the same period 50 age-matched anemia patients, 50 lymphoma patients, 50 leukemia patients, and 50 myelodysplastic syndrome (MDS) patients were selected as control groups. All the patients met WHO disease classification, and were definitely diagnosed by pathology or bone marrow smear/biopsy. The changes of C1q between MM patients and control group, as well as in different therapeutic responses of MM patients before and after treatment were compared, also the difference of clinical characteristics among MM patients with different C1q level, so as to analyze risk factors which led to C1q decline. The average value of C1q in MM patients was (128.18±51.24) mg/L, which was significantly lower than control group (P<0.01). The levels of white blood cell, platelet (PLT), hemoglobin (Hb), serum calcium, albumin, lactate dehydrogenase (LDH) in newly diagnosed high C1q group were significantly higher than those in low C1q group (P<0.05). Logistic analysis showed that the levels of PLT, Hb, albumin, and LDH in newly diagnosed high C1q group were higher than those in low C1q group (r=0.248, r=0.394, r=0.405, r=0.295). After treatment, the levels of C1q in MM patients with complete remission and very good partial remission were significantly higher than before treatment (P<0.05), while those with partial remission and stable disease also increased but not significantly (P>0.05). The C1q level in MM patients is significantly lower than that in patients with other hematologic system diseases, and it increases with the remission of the disease after treatment.

Circulating Levels of Anti-C1q and Anti-Factor H Autoantibodies and Their Targets in Normal Pregnancy and Preeclampsia.

Preeclampsia (PE) generally manifests in the second half of pregnancy with hypertension and proteinuria. The understanding of the origin and mechanism behind PE is incomplete, although there is clearly an immune component to this disorder. The placenta constitutes a complicated immune interface between fetal and maternal cells, where regulation and tolerance are key. Stress factors from placental dysfunction in PE are released to the maternal circulation evoking the maternal response. Several complement factors play a role within this intricate landscape, including C1q in vascular remodeling and Factor H (FH) as the key regulator of alternative pathway complement activation. We hypothesize that decreased levels of C1q or FH, or disturbance of their function by autoantibodies, may be associated with PE. Autoantibodies against C1q and FH and the concentrations of C1q and FH were measured by ELISA in maternal sera from women with preeclamptic and normal pregnancies. Samples originated from cohorts collected in the Netherlands (n=63 PE; n=174 control pregnancies, n=51 nonpregnant), Finland (n=181 PE; n=63 control pregnancies) and Norway (n=59 PE; n=27 control pregnancies). Serum C1q and FH concentrations were higher in control pregnancy than in nonpregnant women. No significant differences were observed for serum C1q between preeclamptic and control pregnancy in any of the three cohorts. Serum levels of FH were lower in preeclamptic pregnancies compared to control pregnancies in two of the cohorts, this effect was driven by the early onset PE cases. Neither anti-C1q autoantibodies nor anti-FH autoantibodies levels differed between women with PE and normal pregnancies. In conclusion, levels of anti-C1q and anti-FH autoantibodies are not increased in PE. C1q and FH are increased in pregnancy, but importantly, a decrease in FH concentration is associated with PE.

Natural antibody IgG levels are associated with HBeAg-positivity and seroconversion in chronic hepatitis B patients treated with entecavir

B1 cell-derived natural antibodies are non-specific polyreactive antibodies and can activate the complement pathway leading to lysis of enveloped virus particles before activation of the adaptive immune response. We investigated the relationship between natural antibody levels and treatment outcomes of 126 treatment-naïve chronic hepatitis B (CHB) patients, who underwent entecavir (ETV) treatment. Serum IgG1-3 and complement C3 levels were significantly higher in HBeAg-positive patients. In pre-treatment, IgG1 (odd ratios [OR] 2.3, p < 0.0001), IgG2 (OR 9.8, p < 0.0001), IgG3 (OR 7.4, p < 0.0001), and C3 (OR 7.2, p < 0.0001) were associated with HBeAg-positive patients. At baseline, IgG2 (OR 10.2, p = 0.025), IgG4, (OR 3.4, p = 0.026), and complement C1q (OR 5.0, p = 0.0068) were associated with seroconverters. Post-treatment levels of IgG1-4 and C3/C1q were also associated with HBeAg-positive patients and seroconverters. High levels of IgG2-4 and C1q were observed in seroconverters but not in virological responders. Thus, high pretreatment and post-treatment levels of natural antibody IgG1-4, complement C3, and/or C1q were significantly associated with HBeAg-positivity and HBeAg seroconverters in CHB patients with ETV treatment. These results suggest that the presence of preexisting host immunity against chronic hepatitis B is closely related to outcome of ETV treatment.

Contribution of Coronavirus-Specific Immunoglobulin G Responses to Complement Overactivation in Patients with Severe Coronavirus Disease 2019.

BackgroundExcessive complement activation has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19), but the mechanisms leading to this response remain unclear.MethodsWe measured plasma levels of key complement markers, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies against SARS-CoV-2 and seasonal human common cold coronaviruses (CCCs) in hospitalized patients with COVID-19 of moderate (n = 18) and critical severity (n = 37) and in healthy controls (n = 10).ResultsWe confirmed that complement activation is systemically increased in patients with COVID-19 and is associated with a worse disease outcome. We showed that plasma levels of C1q and circulating immune complexes were markedly increased in patients with severe COVID-19 and correlated with higher immunoglobulin (Ig) G titers, greater complement activation, and higher disease severity score. Additional analyses showed that the classical pathway was the main arm responsible for augmented complement activation in severe patients. In addition, we demonstrated that a rapid IgG response to SARS-CoV-2 and an anamnestic IgG response to the nucleoprotein of the CCCs were strongly correlated with circulating immune complex levels, complement activation, and disease severity.ConclusionsThese findings indicate that early, nonneutralizing IgG responses may play a key role in complement overactivation in severe COVID-19. Our work underscores the urgent need to develop therapeutic strategies to modify complement overactivation in patients with COVID-19.

Different Complement Activation Pathways Underly Cognitive Impairment and Type 2 Diabetes Mellitus Combined With Cognitive Impairment.

BackgroundThe immune response and the complement system are associated with cognitive impairment and diabetes mellitus, respectively. Activation of the complement system in these diseases occurs mainly through either the classical pathway or the alternative pathway. However, the specific complement proteins involved in the development of the type 2 diabetes mellitus (T2DM) and cognitive impairment are still unclear. Here, we investigated complement proteins in serum from patients with T2DM, cognitive impairment, or both T2DM and cognitive impairment.ObjectiveTo investigate the levels of serum immune complement proteins in patients with T2DM, cognitive impairment, or T2DM combined with cognitive impairment and the associations between these complement proteins and risk factors for T2DM or cognitive impairment.MethodsClinical markers were collected from blood samples of 264 participants. Luminex multiplex assays were used to detect serum complement proteins. All statistical analyses were performed using Prism or R studio.ResultsThere was a difference in serum levels of the complement proteins C1q, C3, C3b, and FH between the three different groups. Hyperglycemia was significantly correlated with elevated C3b or reduced C3, C1q, and FH. In addition, hyperlipidemia was positively correlated with elevated levels of C3, C4, C1q, and FH proteins. There was an association between C1q, C3, C4, and FH and β-pancreas cell function, whereas only FH was associated with insulin resistance. Higher serum C1q was significantly associated with an increased risk of cognitive impairment.ConclusionSerum levels of complement proteins were closely associated with hyperglycemia and hyperlipidemia. We found that classical complement pathway activation mainly occurred in the cognitive impairment only group, whereas the alternative pathway may reflect T2DM and T2DM with cognitive impairment.

Diversity of complement activation in different thyroid diseases

ObjectiveTo investigate complement components expression in both thyroid tissues and serum from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD), and papillary thyroid cancer (PTC). MethodsC1q, mannose binding lectin (MBL), Bb, C4d, C3d and membrane attack complex (MAC) (C5b-9) deposition and complement regulate proteins (CD46, CD55 and CD59) expression in thyroid tissues from HT, GD, PTC, and control groups were examined by IHC. C1q, MBL, Bb, C4d, C3a, and soluble C5b-9 (sC5b-9) serum levels in the HT, GD, PTC, and healthy donor (HD) groups were measured by ELISAs. ResultsMAC deposition was detected in thyroid tissues in the HT, GD and PTC groups, but not the control group. MBL, Bb, C4d, C3d and MAC staining intensities in thyroid tissues were significantly higher in the HT and PTC groups than in the control group (all P < 0.05). The C1q level was higher in HT tissues than in control tissues (both P < 0.05). No complement component had a significant difference in staining intensities between the GD and control groups. CD55 and CD59 expression levels in thyroid tissues were higher in the PTC group than in the HT, GD and control groups (all P < 0.05). Similarly, CD46 levels were higher in HT tissues than in control tissues. Bb, C4d, C3a and sC5b-9 serum levels were significantly increased in HT, GD and PTC patients compared with HDs (all P < 0.05). ConclusionComplement is overactivated in HT and PTC, but not in GD. All the three pathways are activated in HT, and the MBL and alternative complement pathways are activated in PTC. These distinct complement activation profiles may participate in HT, GD and PTC pathogenesis.

Activation of Complement Components on Circulating Blood Monocytes From COVID-19 Patients.

The coronavirus disease-2019 (COVID-19) caused by the SARS-CoV-2 virus may vary from asymptomatic to severe infection with multi-organ failure and death. Increased levels of circulating complement biomarkers have been implicated in COVID-19-related hyperinflammation and coagulopathy. We characterized systemic complement activation at a cellular level in 49-patients with COVID-19. We found increases of the classical complement sentinel C1q and the downstream C3 component on circulating blood monocytes from COVID-19 patients when compared to healthy controls (HCs). Interestingly, the cell surface-bound complement inhibitor CD55 was also upregulated in COVID-19 patient monocytes in comparison with HC cells. Monocyte membrane-bound C1q, C3 and CD55 levels were associated with plasma inflammatory markers such as CRP and serum amyloid A during acute infection. Membrane-bounds C1q and C3 remained elevated even after a short recovery period. These results highlight systemic monocyte-associated complement activation over a broad range of COVID-19 disease severities, with a compensatory upregulation of CD55. Further evaluation of complement and its interaction with myeloid cells at the membrane level could improve understanding of its role in COVID-19 pathogenesis.

Comparison of Complement Pathway Activation in Autoimmune Glomerulonephritis

IntroductionStudies on complement activation have implicated a combination of the classical pathway (CP), lectin pathway (LP), and alternative pathway (AP) in triggering the terminal pathway (TP) for each common autoimmune glomerulonephritis (GN). Evaluating different pathways simultaneously may help identify whether one is preferentially activated and, consequently, which is best to target for each disease.MethodsWe followed 112 patients with focal segmental glomerular sclerosis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), lupus nephritis (LN), and antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) for a median duration of 22 (12–52) months. At the time of greatest clinical activity, we simultaneously evaluated urinary C3a (C3 convertase activity), C5a and sC5b-9 (TP), MASP-1 and MASP-2 (LP), C1q (CP), C4a (CP/LP), and Ba and Bb (AP). We evaluated the relation between activation fragments of the AP and CP/LP with the TP.ResultsUrinary complement biomarkers for each pathway were associated with the severity of proteinuria. Fragments of the TP were higher among patients with FSGS and MN compared with patients with IgAN, LN, and AAV. For the AP, urinary Ba level was lower in those with IgAN and LN compared with those with FSGS. For the CP/LP, urinary C4a, MASP-1, and MASP-2 levels were similar between diseases whereas urinary C1q levels were lower in those with LN. For each GN, independent associations existed between the activation markers of the AP and CP/LP with the degree of TP activation, except for the AP in AAV, although perhaps underpowered.ConclusionThe AP and CP/LP contribute individually to the TP activation in autoimmune GN, and both seem to be valid potential therapeutic targets.

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.

High complement protein C1q levels in pulmonary fibrosis and non-small cell lung cancer associated with poor prognosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is the most common type of interstitial pneumonia. Lung cancer, mainly non-small cell lung cancer (NSCLC), is a complication of idiopathic pulmonary fibrosis. IPF is also an independent risk factor of lung cancer. Some studies have shown that the complement system can promote the progression of interstitial pulmonary fibrosis. In addition, C1q has also demonstrated to exert a tumor-promoting effect in many tumors. However, the role of C1q in idiopathic pulmonary fibrosis and lung cancer still remain unclear.MethodsWe selected common differentially expressed genes in IPF and non-small cell lung cancer using datasets from GEO, and investigated common hub gene. The hub genes were validated in IPF by establishing mouse model of IPF and using another four datasets from the GEO. Multiple databases were analyzed including those of Kaplan–Meier Plotter, Tumor Immune Estimation Resource (TIMER2.0) and the Human Protein Atlas (HPA) for NSCLC.ResultsIn this study, 37 common DEGs were identified in IPF and NSCLC including 32 up-regulated genes and 5 down-regulated genes, and C1q was identified as common hub gene. The methylation status of C1q decreased and the expression levels of C1q increased in both lung cancer and idiopathic pulmonary fibrosis. The prognosis of non-small cell lung cancer and IPF patients with high levels of C1q is poor.ConclusionsThese results show that C1q participates in pulmonary fibrosis and non-small cell lung cancer, and may be a potential diagnostic / prognostic biomarker or a therapeutic target.

Classical complement pathway factor alterations in narcolepsy.

Narcolepsy is a chronic sleep disorder long hypothesised to be an autoimmune disease. Complement-mediated immune mechanisms have not been investigated in detail in narcolepsy. Our aim was to establish the significance of classical pathway activation in narcolepsy. Sera of 42 narcolepsy patients and 26 healthy controls were screened with ELISA to determine the levels of C1q, C3a, C4d and complement component 4 binding protein (C4BP). A home-made ELISA method was developed to detect antibodies to C4BP-alpha (anti-C4BPA). The correlation between complement levels and clinical findings was examined. C1q levels were significantly higher in narcolepsy patients while C4d and C4BP levels were significantly lower compared to healthy controls. C3a levels were comparable among patients and controls. Eleven narcolepsy patients showed serum anti-C4BPA levels. Total rapid eye movements (REM) time, sleep onset latency, REM sleep latency, sleep activity, percentage of wakefulness after sleep onset and Epworth sleepiness scale scores were correlated with levels of different complement factors. Complement-mediated immune mechanisms might partake in narcolepsy pathogenesis. The precise role of autoantibodies on complement level alterations needs to be investigated. Levels of complement factors and degradation products may potentially be utilised as biomarkers to predict the clinical severity of narcolepsy.

Association of C1q gene cluster variants with rheumatoid arthritis: a pilot study.

Single-nucleotide polymorphisms (SNPs) in C1q gene cluster were previously linked to autoimmunity and SLE, but data are scarce for their association with RA. In the present study, we evaluated associations of five SNPs (rs665691, rs682658, rs172378, rs292001 and rs294179) in the C1q genetic region with RA and some of its clinical and immunologic characteristics. Fifty-eight RA patients and 67 age- and gender-matched healthy controls, all Caucasian, participated in the study. They were genotyped for the five SNPs using TaqMan allelic discrimination assay, and their C1q levels were estimated by ELISA. Rheumatoid factor and anti-citrullinated peptide antibodies were measured (using latex agglutination and ELISA resp.) in the RA patients' group and relevant clinical information was collected. RA patients and healthy controls had similar frequencies of alleles and genotypes of rs665691, rs682658 and rs294179. Minor G-allele and GG genotype of rs172378 were associated with RA (OR = 2.80; 95% CI 1.62-4.81; p = 0.0002 and OR = 5.01; 95% CI 1.55-16.24; p = 0.007, resp.), as well as AA genotype of rs292001 (OR = 3.23; 95% CI 1.15-9.08; p = 0.026). C1q levels were significantly lower (still normal) in RA patients' group compared to healthy volunteers: 89µg/ml (68-121) vs 114µg/ml (60-169), p < 0.0001. Significant association was established between rs172378 and rs292001 and RA, in contrast to rs665691, rs682658 and rs294179. RA patients had lower C1q levels than healthy controls. Our findings correspond to the scientific knowledge so far and add additional clarity from a Bulgarian cohort.

Serum complement component 3, complement component 4 and complement component 1q levels predict progressive visual field loss in older women with primary angle closure glaucoma

AimTo evaluate the association between serum levels of complement component (C) 3, C4 and C1q and visual field (VF) loss in patients with primary angle closure glaucoma (PACG).MethodsIn this prospective...

Identification of biomarkers of chronic kidney disease among kidney-derived proteins

BackgroundChronic kidney disease (CKD) has few objective symptoms, and it is difficult to make an early diagnosis by using existing methods. Therefore, new biomarkers enabling diagnosis of renal dysfunction at an early stage need to be developed. Here, we searched for new biomarkers of CKD by focusing on kidney-derived proteins that could sensitively reflect that organ’s disease state.MethodsTo identify candidate marker proteins, we performed a proteomics analysis on renal influx and efflux blood collected from the same individual.ResultsProteomics analysis revealed 662 proteins in influx blood and 809 in efflux. From these identified proteins, we selected complement C1q as a candidate; the plasma C1q level was significantly elevated in the renal efflux of donors. Moreover, the plasma concentration of C1q in a mouse model of diabetic nephropathy was significantly increased, in association with increases in blood glucose concentration and urinary protein content. Importantly, we demonstrated that the tendency of C1q to increase in the plasma of CKD patients was correlated with a decrease in their estimated glomerular filtration rate.ConclusionOverall, our results indicate that our approach of focusing on kidney-derived proteins is useful for identifying new CKD biomarkers and that C1q has potential as a biomarker of renal function.

Association of Serum Complement C1q and C3 Level with Age-Related Macular Degeneration in Women

PurposeTo investigate the association between serum complement components and age-related macular degeneration (AMD).Patients and MethodsA total of 118 AMD patients and age- and sex-matched 106 control subjects were included. Demographic data and the level of serum complement component (C)1q, C3 and C4 were evaluated. Based on sex, the subjects were stratified into male and female subgroups.ResultsThe level of C1q (226.31±45.33mg/dL) was significantly higher and C3 (121.14±15.76mg/dL) was significantly lower than that in control group (200.03±38.54mg/dL) (128.42±19.81mg/dL) in the female AMD patients (p = 0.005, p = 0.045). Logistic regression showed that increased C1q (OR = 1.132, p = 0.016) and decreased C3 (OR = 0.960, p = 0.048) were independent risk factors for female AMD patients. No statistical significance was observed in the male.ConclusionIncreased C1q and decreased C3 were associated with increased risk of AMD, suggesting that the complement classical pathway probably be involved in AMD, especially in female.

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.