Serum C3 Research Articles

The correlation of anxiety and depression with C3 and C4 Levels and systemic lupus erythematosus activity

BackgroundAnxiety and depression are psychosomatic disorders that are frequently observed in chronic conditions such as systemic lupus erythematosus (SLE). Anxiety and depression can be induced by immunological and neurotransmitter dysregulation, which is characterized by hypothalamic–pituitary–adrenal (HPA) axis dysfunction, production of proinflammatory cytokines, and activation of complement in the blood, such as C3 and C4. The causes of anxiety and depression in SLE are complex, ranging from neuropsychiatric involvement to drug adverse effects. Detecting anxiety and depression symptoms in SLE patients is critical to preventing disability from impacting quality of life.ObjectiveTo assess the relationship between anxiety and depression symptomatology, SLE disease activity with levels of C3 and C4 in Cipto Mangunkusumo National Hospital.MethodsThis study used a cross-sectional design. The study included 120 SLE patients from Cipto Mangunkusumo National Hospital, aged 18 to 60 years. All patients were requested to complete a Hospital Anxiety and Depression Scale (HADS) questionnaire to assess their anxiety and depression symptoms. Subjects with anxiety and depression were assessed for disease activity using the Mexican Systemic Lupus Erythematosus Systemic Disease Activity (Mex-SLEDAI), and blood samples were collected to test complement C3 and C4 levels. Spearman's correlation test was used to examine the relationship between HADS scores, Mex-SLEDAI, and C3 and C4 levels.ResultsThe results of the study showed a very weak statistically significant negative correlation between anxiety symptoms based on HADS and C3 levels (r = -0.189; p = 0.038) and a weak correlation between anxiety symptoms and C4 levels (r = -204; p = 0.026). Depressive symptoms based on HADS revealed a very poor connection and no statistical significance with levels of C3 (r = -0.056; p = 0.546) and C4 (r = -0.068; p = 0.461). Anxiety (r = 0.06; p = 0.173) and depression (r = 0.031; p = 0.753) symptoms have a weak and insignificant positive connection with SLE activity.ConclusionC3 and C4 serum levels appeared to decrease when the presence of anxious symptoms increased. There was no significant correlation in SLE disease activity between anxious and depressed patients.

Are serum C3 levels or kidney C3 deposits useful markers for predicting outcomes in patients with ANCA-associated vasculitis?

IntroductionComplement activation emerged as a key actor of anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV). Whether serum levels of C3 (sC3) or C3 kidney deposition may help to refine the prognosis of AAV remains elusive. MethodsRetrospective multicentric study that included 154 patients with a first flare of AAV and sC3 (n = 143) or C3 kidney staining (n = 95) available at diagnosis. Clinical presentations, kidney pathology, and survival of patients with normal or low sC3 were compared using univariate analyses, Kaplan-Maier curves with log-rank comparison, or multivariate Cox’ model, as appropriate. Results20 patients (14 %) had low sC3. sC3 (as bivariate low/normal or as a continuous variable) was associated with 5-year mortality but not with kidney survival. C3 kidney deposition (C3+) was identified in 23 patients who were characterized by more frequent chronic hypertension and lower eGFR at presentation (p = 0.04). C3+ correlated with IgG, IgM, C1q deposition (p = 0.07, p < 0.0001 and p = 0.003, respectively). Chronicity and activity scores were similar in C3+ and C3- patients. Among C3+ patients, those with C3 deposition ≥2+ had lower eGFR at presentation (p = 0.006) and were more frequently classified as sclerotic using the Berden classification (p = 0.04) and as ‘high risk’ using the Brix score (p = 0.03). However, eGFR improvement following induction regimen was similar between C3+ and C3- patients, and kidney survival at 5 years was similar. ConclusionsCorrelation of sC3 with mortality confirms mechanistic links between complement pathways and AAV, but the lack of clear predictive sC3 cut-off and the similar kidney outcome irrespective of C3 deposition precludes their use as biomarkers of AAV outcomes and response to treatment.

Clinical Characteristics of Retroperitoneal Fibrosis Patients at a Tertiary Hospital in Japan.

Retroperitoneal fibrosis (RPF) is a rare cause of hydronephrosis and progressive renal dysfunction with unidentified origin. RPF is categorized into idiopathic RPF with/without immunoglobulin G4 (IgG4)-related disease (IgG4-RD), and secondary RPF. Identifying the underlying cause is challenging and often associated with delayed diagnosis or therapeutic interventions. We investigated RPF's clinical characteristics based on different etiologies and factors that may help distinguish the underlying causes. We analyzed the cases of 49 patients with RPF that was radiographically diagnosed at our institution (2008-2022). The cohort was 77.6% males; 75.5% had idiopathic RPF and 24.5% had secondary RPF. Among the idiopathic patients, 54.1% had IgG4-RD. The patients were likely to have abdominal pain, lower back pain/lumbago, and constitutional symptoms including generalized fatigue and fever. The idiopathic patients were likely to have higher serum IgG4 and IgG levels and lower serum C3 levels compared to secondary RPF. The IgG4-RPF patients were likely to have higher serum IgG4 levels and lower serum C-reactive protein, ferritin, and C3 levels compared to the idiopathic RPF patients without IgG4-RD. These findings might reflect underlying systemic inflammatory responses. Comprehensive laboratory testing, including serum inflammatory markers and immunological panels, is recommended for radiologically diagnosed RPF patients.

High-dimensional analysis of T-cell profiling variations following belimumab treatment in systemic lupus erythematosus

ObjectiveThis study sought to elucidate the molecular impacts of belimumab (BEL) treatment on T-cell immune profiling in SLE.MethodsWe used mass cytometry with 25 marker panels for T-cell immune profiling in...

The correlation between trajectories of serum C3 variability and clinical course in Pediatric-onset systemic lupus erythematosus.

The aim of this study is to investigate the usefulness which 2-year trajectories of C3 variability have in predicting clinical remission and systemic corticosteroids (SCS) use in pediatric patients with systemic lupus erythematosus (pSLE). We recruited 189 confirmed pSLE patients from the electronic database of our hospital, all had undergone SCS treatment. The follow up period was 4.17-14.83 years. We used Group-Based Trajectory modeling to divide the patients into four different trajectory groups by their initial 2-year C3 variability. We divided the patients into groups A, B or C by their clinical course and SCS use. Statistical methods included Kruskal-Wallis and Chi-square tests and logic regression test. There were 4 separate trajectories. The distribution of groups A, B and C in these 4 trajectories showed a significant difference (p=0.005). Initial C3 and C4 levels in these 4 revealed significant differences (p≦0.001, p≦0.016). When compared to other trajectories, trajectory1 showed a higher risk for persistent SCS use (p<0.05). The distributions of severe clinical manifestations, including proteinuria, hematuria, CNS involvement and thrombocytopenia were different in these 4 trajectories (p=0.003). Nevertheless, none of the above manifestations contributed to the risk of persistent SCS use. We have found 4 distinct C3 trajectories in pSLE patients. Distributions of clinical outcome groups were different in these 4 trajectories. Patients with trajectory1 displayed a higher risk for persistent SCS use, thus an earlier institution of immunosuppressant(s) and biological agents can be considered for these children.

Clinical and pathological features of omicron variant of SARS-CoV-2-associated kidney injury.

Kidney injury is common in patients with Coronavirus Disease-19 (COVID-19), which is related to poor prognosis. We aim to summarize the clinical features, athological types, and prognosis of COVID-19 associated kidney injury caused by the Omicron strain. In this study, 46 patients with Omicron-associated kidney injury were included, 38 of whom performed renal biopsy. Patients were divided into twogroups: group A for patients with onset of kidney injury after SARS-CoV-2 infection; group B for patients with pre-existing kidney disease who experienced aggravation of renal insufficiency after SARS-CoV-2 infection. The clinical, pathological, and prognostic characteristics of the patients were observed. Acute kidney injury (AKI) (35%) was the mostcommon clinical manifestation in group A. Patients in group B mainly presented with chronickidney disease(CKD)(55%)and nephroticsyndrome (NS)(40%). The pathological type was mainly IgA nephropathy (IgAN) (39% in group A and 45% in group B). Among all of them, one case presenting with thrombotic microangiopathyhad worse kidney function at biopsy time. Mean serum C3 levels were 1.2 ± 0.5 and 1.0 ± 0.2 g/L in group A and group B, respectively. In renal tissues, C3 deposits were observed in 71.1% of patients. 11.8% (n = 2) patients experienced deterioration of renal function after treatment, but no patients developed to end-stage renal disease. In our single-center study in China, the main clinical manifestations were AKI, CKD, and NS, while the main pathological type was IgAN. Compared with previous strains of SARS-CoV-2, patients with the Omicron infection had a favorable prognosis.

Study of the Levels of Immunoglobulin G and Complement 3 in Gestational Diabetes and Their Newborn

Background: The most typical metabolic issue related to pregnancy is gestational diabetes. Because it eliminates undesired germs and causes inflammation, the complement system (C3) is an essential part of the cellular immune system. It has been linked to metabolic diseases, including diabetes, obesity, dyslipidemia, insulin resistance, and liver dysfunction. C3 is also becoming more well recognized as a risk factor for cardiovascular and metabolic diseases. Immunoglobulin levels in maternal blood and colostrum are decreased by hyperglycemia, which also affects IgG transfer across the placenta. Aim of study: to compare the levels of C3 and immunoglobulin G in the sera of pregnant women with gestational diabetes and their babies to pregnant women without the disease. Methods: a case control study that was carried out over the course of four months, from August 18 to December 20, 2020, at the department of obstetrics and gynecology at Salahaddin General Hospital/Salahaddin. It involved 92 pregnant women who separated into two groups and went to the delivery room to deliver a viable fetus: 47 pregnant women in the case group had been diagnosed with gestational diabetes mellitus, whereas the 45 pregnant women in the control group had no complaints and were matched with the other groups' ages and gestational ages. Results for C3 and IgG levels in maternal and cord blood were noted. Results: In this study, the case group's mean birthweight and maternal serum C3 levels were both considerably greater than those of the controls. The mean cord serum IgG level in the case group was substantially lower than that in the controls. Conclusion: Understanding the underlying chronic inflammation that affects the developing fetus' innate immune system and predisposes the person to future diabetes and its consequences may be possible with complement C3 estimate in GDM.

Serum Complement C4 Levels Are a Useful Biomarker for Predicting End-Stage Renal Disease in Microscopic Polyangiitis.

This study aimed to evaluate the risk factors for end-stage renal disease (ESRD) in microscopic polyangiitis (MPA). In total, 74 patients with MPA were enrolled, and we compared the baseline clinical characteristics and disease activity between MPA patients who have progressed to ESRD and those without ESRD to select predictive factors for ESRD. Out of 74 patients, 12 patients (16.2%) had ESRD during follow-up. Serum C4 levels were significantly higher in MPA patients who have progressed to ESRD than in those without ESRD (p = 0.009). Multivariate analyses revealed that high serum creatinine levels (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.25-15.5) and high serum C4 levels (OR 1.24, 95% CI 1.03-1.49) were risk factors for ESRD. Using receiver operating characteristic analysis, the cut-off value for initial serum C4 levels and serum creatinine levels were 29.6 mg/dL and 3.54 mg/dL, respectively. Patients with MPA with a greater number of risk factors (serum C4 levels > 29.6 mg/dL and serum creatinine levels > 3.54 mg/dL) had a higher ESRD progression rate. Serum C4 levels were significantly positively correlated with serum creatinine levels and kidney Birmingham vasculitis activity score (p = 0.02 and 0.04, respectively). These results suggest that serum C4 levels are useful tools for assessing renal disease activity and prognosis in MPA.

Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy

Complement 3 glomerulopathy (C3G) is a rare inflammatory kidney disease mediated by dysregulation of the alternative complement pathway. No targeted therapy exists for this aggressive glomerulonephritis. Efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) (measured by complement biomarkers) of iptacopan were assessed in patients with C3G. In this phase 2, multicenter, open-label, single-arm, nonrandomized study, adults with biopsy-proven, native kidney C3G (native cohort) and kidney transplant recipients with C3G recurrence (recurrent kidney transplant [KT] cohort) received iptacopan twice daily (bid) for 84 days (days 1-21: 10-100 mg; days 22-84: 200 mg). The primary end point was the urine protein-to-creatinine ratio (UPCR; native cohort) and the change in the C3 deposit score of kidney biopsy (recurrent KT cohort). The complement pathway measures included Wieslab assay, soluble C5b9, and serum C3 levels. A total of 27 patients (16 native cohort and 11 recurrent KT cohort) were enrolled and all completed the study. In the native cohort, UPCR levels decreased by 45% from baseline to week 12 (P= 0.0003). In the recurrent KT cohort, the median C3 deposit score decreased by 2.50 (scale: 0-12) on day 84 versus baseline (P= 0.03). Serum C3 levels were normalized in most patients; complement hyperactivity observed pretreatment was reduced. Severe adverse events (AEs) included post-biopsy hematuria and hyperkalemia. No deaths occurred during the study. Iptacopan resulted in statistically significant and clinically important reductions in UPCR and normalization of serum C3 levels in the native cohort and reduced C3 deposit scores in the recurrent KT cohort with favorable safety and tolerability. (ClinicalTrials.gov identifier: NCT03832114).

Prospects and Pitfalls of Plasma Complement C4 in Schizophrenia: Building a Better Biomarker

Complex brain disorders like schizophrenia may have multifactorial origins related to mis-timed heritable and environmental factors interacting during neurodevelopment. Infections, inflammation, and autoimmune diseases are over-represented in schizophrenia leading to immune system-centered hypotheses. Complement component C4 is genetically and neurobiologically associated with schizophrenia, and its dual activity peripherally and in the brain makes it an exceptional target for biomarker development. Studies to evaluate the biomarker potential of plasma or serum C4 in schizophrenia do so to understand how peripheral C4 might reflect central nervous system-derived neuroinflammation, synapse pruning, and other mechanisms. This effort, however, has produced mostly conflicting results, with peripheral C4 sometimes elevated, reduced, or unchanged between comparison groups. We undertook a pilot biomarker development study to systematically identify sociodemographic, genetic, and immune-related variables (autoimmune, infection-related, gastrointestinal, inflammatory), which may be associated with plasma C4 levels in schizophrenia (SCH; n = 335) and/or in nonpsychiatric comparison subjects (NCs; n = 233). As with previously inconclusive studies, we detected no differences in plasma C4 levels between SCH and NCs. In contrast, levels of general inflammation, C-reactive protein (CRP), were significantly elevated in SCH compared to NCs (ANOVA, F = 20.74, p < 0.0001), suggestive that plasma C4 and CRP may reflect different sources or causes of inflammation. In multivariate regressions of C4 gene copy number variants, plasma C4 levels were correlated only for C4A (not C4B, C4L, C4S) and only in NCs (R Coeff = 0.39, CI = 0.01–0.77, R² = 0.18, p < 0.01; not SCH). Other variables associated with plasma C4 levels only in NCs included sex, double-stranded DNA IgG, tissue-transglutaminase (TTG) IgG, and cytomegalovirus IgG. Toxoplasma gondii IgG was the only variable significantly correlated with plasma C4 in SCH but not in NCs. Many variables were associated with plasma C4 in both groups (body mass index, race, CRP, N-methyl-D-aspartate receptor (NMDAR) NR2 subunit IgG, TTG IgA, lipopolysaccharide-binding protein (LBP), and soluble CD14 (sCD14). While the direction of most C4 associations was positive, autoimmune markers tended to be inverse, and associated with reduced plasma C4 levels. When NMDAR-NR2 autoantibody-positive individuals were removed, plasma C4 was elevated in SCH versus NCs (ANOVA, F = 5.16, p < 0.02). Our study was exploratory and confirmation of the many variables associated with peripheral C4 requires replication. Our preliminary results point toward autoimmune factors and exposure to the pathogen, T. gondii, as possibly significant contributors to variability of total C4 protein levels in plasma of individuals with schizophrenia.

A retrospective study of myelin oligodendrocyte glycoprotein antibody-associated disease from a clinical laboratory perspective.

To analyze the differences in laboratory data between patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The study included 26 MOGAD patients who visited Beijing Tiantan Hospital from 2018 to 2021. MS and NMOSD patients who visited the clinic during the same period were selected as controls. Relevant indicators were compared between the MOGAD group and the MS/NMOSD groups, and the diagnostic performance of meaningful markers was assessed. The MOGAD group showed a slight female preponderance of 57.7%, with an average onset age of 29.8 years. The absolute and relative counts of neutrophils were higher in the MOGAD group than in the MS group, while the proportion of lymphocytes was lower. The cerebrospinal fluid (CSF) IgG level, IgG index, 24-h IgG synthesis rate, and positive rate of oligoclonal bands (OCB) were lower in MOGAD patients than in the MS group. The area under ROC curve (AUC) was 0.939 when combining the relative lymphocyte count and IgG index. Compared to the NMOSD group, the MOGAD group had higher levels of serum complement C4 and lower levels of serum IgG. The AUC of serum C4 combined with FT4 was 0.783. Statistically significant markers were observed in the laboratory data of MOGAD patients compared to MS/NMOSD patients. The relative lymphocyte count combined with IgG index had excellent diagnostic efficacy for MOGAD and MS, while serum C4 combined with FT4 had better diagnostic efficacy for MOGAD and NMOSD.

Alleviative effect of poly-β-hydroxybutyrate on lipopolysaccharide-induced oxidative stress, inflammation and cell apoptosis in Cyprinus carpio

In this study, the alleviative effects of poly-β-hydroxybutyrate (PHB) in bioflocs on oxidative stress, inflammation and apoptosis of common carp (Cyprinus carpio) induced by lipopolysaccharide (LPS) were evaluated. Common carp were irregularity divided into 5 groups and fed five diets with 0 % (CK), 2 %, 4 %, 6 % and 8 % PHB. After 8-week feeding trial, LPS challenge was executed. Results showed that appropriate level of PHB enhanced serum immune function by reversing LPS-induced the decrease of C3, C4, IgM, AKP, ACP and LZM in serum, alleviated LPS-induced intestinal barrier dysfunction by decreasing the levels of 5-HT, D-LA, ET-1 and DAO in serum, increasing ZO-1, Occludin, Claudin-3 and Claudin-7 mRNA, improving intestinal morphology. Moreover, dietary PHB reversed LPS-induced the decrease of AST and ALT in hepatopancreas, while in serum exhibited the opposite trend. Suitable level of PHB reversed LPS-induced the reduction of GSH-PX, CAT, T-SOD and T-AOC in intestines and hepatopancreas, whereas MDA showed the opposite result. PHB alleviated LPS-induced the decrease of Nrf2, HO-1, CAT, SOD and GSH-PX mRNA, the increase of Keap1 mRNA. Appropriate level of PHB alleviated LPS-induced inflammation and apoptosis by up-regulating TGF-β, IL-10 and Bcl-2 mRNA, down-regulating NF-κB, TNF-α, IL-6, Bax, Caspase-3, Caspase-8 and Caspase-9 mRNA. Furthermore, PHB inhibited activation of NLRP3 inflammasomes by reducing the levels of NLRP3, Caspase-1, ASC, IL-1β and IL-18 mRNA and protein. In addition, the increases of dietary PHB linearly and quadratically affected LPS-induced adverse effects on common carp. Summary, this study suggested that appropriate level of dietary PHB alleviated LPS-induced oxidative stress, inflammation, apoptosis and the activation of NLRP3 inflammasome in common carp. And the appropriate level of PHB in common carp diets was 4 %.

Association of STAT3 gene polymorphisms with systemic lupus erythematosus in a Chinese Han population.

Evidence supports the important role of STAT3 in SLE; however, association between STAT3 gene polymorphisms and SLE risk needs discussion. Three hundred SLE patients and 380 healthy controls from Chinese Han population were included. DNA is extracted from peripheral blood mononuclear cells and the clinical characteristics of patients are collected. STAT3 gene polymorphisms (rs6503695, rs744166, rs9912773, and rs12601982) were genotyped by the Kompetitive Allele-Specific PCR (KASP) method. SPSS 26.0 was utilized to analyze the genetic susceptibility of SLE and STAT3 gene polymorphisms. Frequencies of genotypes CT, TT, and TT+CT were significantly lower in SLE patients compared with those in healthy controls with respect to rs6503695 (p = .007, p < .001, p = .001). Frequencies of rs744166 genotypes AG, AA, and AA+AG were decreased in SLE patients as compared to those in healthy controls (p = .034, p = .006, p = .009). The recessive models (CC vs GG+GC) for rs9912773 and (AA vs GG+GA) for rs12601982 were significantly related to SLE patients (p = .014, p = .035). Moreover, allele C of rs6503695 was related to optic nerve damage in SLE patients (p = .036). rs744166 allele G was correlated with positive rash and albuminuria in SLE patients (p = .006, p = .014). For rs9912773, SLE patients carrying genotype GG had higher serum C3 and C4 levels compared to genotype GC+CC (p = .029, p = .028). The rs12601982 allele G was strongly associated with positive hypocomplementemia in SLE patients (p = .034). SLE patients carrying genotypes GG, GC, and CC had different SLEDAI score for rs12601982 (GG vs GC vs CC, p = .003). STAT3 gene polymorphisms associated with SLE susceptibility.

Beneficial effects of indigenous Bacillus spp. on growth, antioxidants, immunity and disease resistance of Rhynchocypris lagowskii

This study aimed to investigate the effect of Bacillus aryabhattai (LSG3-7) and Bacillus mojavensis (LSG3-8) on growth performance, antioxidant capacity, and immune response in Rhynchocypris lagowskii (Dybowski, 1869), at the trial and challenge periods. A 630 healthy fish (10.76 ± 0.05) were randomly divided into six groups: control group (D1) was fed the basal diet, D2 and D3 were supplemented with LSG 3–7 and LSG3-8 (1 × 108 CFU/g) for both of them, whereas D4 was supplemented with a mixture of both bacteria (0.5 × 108 CFU/g each), and D5 was supplemented with LSG3-7 0.75 × 108 CFU/g + LSG3-8 0.25 × 108 CFU/g, and D6 supplemented with LSG3-7 0.25 × 108 CFU/g + LSG3-8 0.75 × 108 CFU/g. After the trial, Aeromonas hydrophila was used in a challenge test for 14 days. Treatments showed significant differences (p < 0.05) in growth performance and antioxidant capacity (CAT, CuZn-SOD, GPX) in the liver and intestine compared to the control. The antioxidant-related genes CAT, CuZn-SOD, GPX, and Nrf2 in the liver and intestine showed upregulation compared with the control group. Serum IgM, LZM, C3, C4, and AKP showed a favorable superiority (p < 0.05) in treatments (D2 – D6) at the trial and challenge test compared to controls. In parallel, immune-related genes (IgM, NF-κB, TLR-1, TLR-2, and MyD88) showed an up-regulated level (p < 0.05) in treatments (D2 – D6) compared to the control. In addition, pro-inflammatory cytokines (IL-1, TNF-α) showed a downregulated level in treatments (D2 – D6). After the challenge test, the immune-related genes in the liver and muscle showed an up-regulated level in treatments compared to the controls. The survival rate showed a significant increase (p < 0.05) in the treatment groups (D2 – D6) compared to the control. Overall, individuals and the bacterial mixture of B. aryabhattai and B. mojavensis could improve the growth performance, antioxidant capacity, immune capacity, and survival rate of R. lagowskii and prevent side effects of A. hydrophila. However, B. mojavensis showed a slight improvement compared to B. aryabhattai without a significant difference between them.

Immunoglobulin A and complement C4 are involved in the progression of liver fibrosis in patients with chronic hepatitis B.

To explore the relationship between immunoglobulin A (IgA), complement C4, and liver fibrosis (L.F.) progression (LFP) in patients with chronic hepatitis B (CHB). This is a retrospective cohort study of CHB patients who received liver biopsies. Relevant data, including demographics, clinical serum markers, and immunological results obtained during liver biopsies, were collected and analyzed to assess and verify the relationship between IgA, C4, and LFP. This study included 1,938 CHB patients, of whom 132 received two liver biopsies (group 1). Thirty (22.7%) of these patients were diagnosed with LFP (increase in L.F. stage (Scheuer score F≥1)). IgA (C-IgA) and C4 (C-C4) change values between the first and second biopsies were independent risk factors for LFP. IgA levels increased, and C4 levels decreased during the second liver puncture. The remaining 1,806 patients received one liver puncture (group 2). They were divided into the following subgroups: A (F≤1), B (1<F≤3), and C (F>3) to verify whether the same trend was observed by cross-sectional study. IgA levels were highest, and C4 levels were lowest in group C (IgA: C>B>A, p<0.05; C4: C<B<A, p<0.05). The findings of this study suggest that serum IgA and C4 levels are independent risk factors for LFP that could serve as future targets for L.F. management and treatment.

Detection of the Serum Level of C3 and C4 Among Patients with Urinary Tract Infection

The current study aims to determine the prevalence of bacterial urinary tract infection (UTI) and estimate the serum levels of C3 and C4 in UTI patients. This study had been included 350 samples (blood and urine) obtained from outpatients suspected of having UTI from Baquba-Teaching Hospital. The detection of causative Bacteria was done using an automatic VITEK 2 system. A sample of 350 urine was taken, and after diagnoses, it found that only 205 (58.5%) had UTI; 123 (as 60 %) with a positive culture of bacteria, and 82 (as 40%) with negative culture of bacteria. Among the Gram-negative bacteria, mostly isolated were Escherichia coli 44 (resembles 35.7%), K. Pneumonia 18 (resembles 14.6%), P. aeruginosa 8 (resembles 6.5%) 2 (resembles 1.6 %) which was diagnosed as Burkholderia cepacia. Gram-positive organisms included 51 (as 41.4%) of total positive results, divided into 37 isolates (30.08%) of Staphylococcus spp. and 14 isolates (11.3%) of Enterococcus spp. Immunological parameters, which were included the determination of serum levels of C3 with C4 showed that lower levels of both C3 and C4 in UTI patients compared with the control group (18.48±1.3 versus 19.4 ± 2.9pg/ml) and (0.739±0.257 versus 1.205±0.259 pg/ml) respectively. In conclusion, E. coli, K. pneumoniae and S. aureus were found to be the highly isolated bacteria in UTI cases, with decreased levels of C3 and C4 in serum in UTI patients.

Clinical Safety and Efficacy of Pegcetacoplan in a Phase 2 Study of Patients with C3 Glomerulopathy and Other Complement-Mediated Glomerular Diseases

Dysregulated complement activation is likely the primary driver of disease in C3 glomerulopathy (C3G) and contributes to other complement-mediated diseases, including immunoglobulin A nephropathy (IgAN), lupus nephritis (LN), and primary membranous nephropathy (PMN). No complement inhibitors are proven to halt disease progression in these diseases. Pegcetacoplan, a targeted C3 and C3b inhibitor, may mitigate complement-mediated kidney damage in C3G and other glomerular diseases in which complement may have a pathogenic role. This open-label, phase 2, 48-week study evaluated the preliminary efficacy and safety of subcutaneous pegcetacoplan for patients with complement-mediated glomerular diseases. The primary end point was proteinuria reduction, measured as 24-hour urine protein-to-creatinine ratio. Secondary end points included remission status, changes in estimated glomerular filtration rate (eGFR), and pharmacodynamic biomarkers. Treatment-emergent adverse events (TEAEs) were monitored. Efficacy results for the C3G cohort are reported herein, along with safety results for the study population. In the C3G cohort, mean proteinuria reduction from baseline to week 48 was 50.9% in the intent-to-treat (ITT) population (n= 7) and 65.4% in the per-protocol (PP) population (n= 4). Mean serum albumin normalized and mean eGFR was stable over 48 weeks. Mean serum C3 levels increased 6-fold and mean soluble C5b-9 levels decreased by 57.3% at week 48. The most common adverse events (AEs) were upper respiratory tract infection, injection site erythema, nausea, and headache. No meningitis or sepsis cases were reported, and no serious treatment-related AEs were observed. Pegcetacoplan may provide therapeutic benefit for C3G and has a favorable safety profile across the 4 glomerular diseases studied.

Effects of dietary zinc levels on growth, intestinal health, antioxidant and non-specific immunity of spotted seabass (Lateolabrax maculatus) reared at two temperatures

This study investigated effects of dietary zinc levels and water temperature on growth, feed utilization, intestinal health, antioxidant and non-specific immunity of spotted seabass. Six experimental diets were formulated to contain 30, 53, 77, 98, 116, or 145 mg Zn/kg. Each diet was fed to two different groups of fish reared at low temperature (27 °C; LT) or high temperature (33 °C; HT). Triplicate groups of fish were fed the test diets to apparent satiation two times daily for 8 weeks. Results showed that fish under HT showed the lower weight gain (WG) and higher feed conversion rate (FCR) comparing to the LT treatment (P < 0.05). Also, the growth and feed utilization were significantly (P < 0.05) influenced by dietary Zn levels and broken-line regression analysis showed the optimal dietary Zn level for spotted seabass reared at 27 °C and 33 °C are 77.69 mg/kg and 93.61 mg/kg, respectively. Apparent digestibility coefficients (ADCs) of protein and lipid in HT treatment were significantly lower than those of LT treatment (P < 0.05), and ADCs significantly increased with the increase of dietary Zn levels. The histology showed HT and Zn-deficiency can cause the damage of intestine, while fish fed 77 mg Zn/kg diets presented normal structure. Serum LZM activity, C3 and IgM contents of HT treatments were lower than those of the LT treatments. Further, LZM activity, C3, and IgM contents can be significantly elevated by the increasing of dietary Zn levels. MDA content of HT treatments were significantly higher than that of LT treatments, while MDA content decreased with the increase of dietary Zn levels as SOD activity and T-AOC increased. Overall, the optimum dietary Zn level alleviated heat stress via enhancing immunity, antioxidant capacity and intestine health.

Risk Factors Analysis for the Development of Hypocomplementemia in Rheumatoid Arthritis Patients: A Single-Center Retrospective Study.

The purpose of the research was to explore the possible risk factors for the development of hypocomplementemia (HC) in rheumatoid arthritis (RA) patients by analyzing their clinical and laboratory features. This retrospective research contained 501 RA patients, divided into RA patients with HC (n=78) and RA patients without HC (n=423). Demographic characteristics and laboratory test results of RA patients were collected and analyzed, such as age, sex, anti-mutated citrullinated vimentin antibody (Anti-MCV), serum complements (C3, C4), immunoglobulins (IgA, IgG, IgM), hemoglobin (Hb), platelets (PLT) and erythrocyte sedimentation rate (ESR), etc. Spearman correlation was served as assessing the correlations of the levels of serum C3 and C4 with each index. Receiver operating characteristic (ROC) curves were served as assessing the diagnostic efficacy of each index for RA patients with HC. Furthermore, risk factors for the occurrence of HC in RA patients were analyzed by employing binary logistic regression of single and multiple factors. Compared RA patients with HC to without HC, the former were older and had a longer disease duration with increased levels of Anti-MCV, IgM and DAS28 and lower levels of Hb, PLT and ESR; Spearman correlation analysis verified the level of serum Anti-MCV was a negative correlation with C3 (r=-0.156); the area under the ROC curve (AUC) of PLT in diagnosing RA patients with HC was the largest at 0.65 (95% CI: 0.60-0.69); binary logistic regression analysis indicated that advanced age (>66 years), long disease duration (>62 months), high DAS28 value (>6.13), the levels of Anti-MCV>107.68IU/mL, IgM>1.54g/L, ESR≤69.00mm/h, Hb≤99.00g/L and PLT≤305.00×109/L were probable risk factors for the occurrence of HC in RA patients. Age and disease duration, DAS28, Anti-MCV, IgM, ESR, Hb, and PLT are closely related to the development of HC in RA patients. Timely monitoring of these indicators can help to evaluate disease activity of RA patients and further improve their prognosis.

Neutrophil extracellular traps involved in the pathogenesis of IgA vasculitis: Confirmed in two IgAV rat models.

Neutrophil extracellular traps (NETs) have been found to play a role in the development of autoimmune diseases. In the past two years, studies have demonstrated a significantly increase of NETs in skin tissues during the early stages of IgAV, indicating their involvement in disease activity among children with IgAV. However, the presence of NETs in IgAV animal models has not yet been reported. The objective of this study is to investigate whether NETs are involved in the pathogenesis of IgA vasculitis (IgAV) rats. Twenty-four SD rats were randomly divided into three groups: the ovalbumin group, the gliadin group, and the control group. The IgAV rat models were established administering Indian ink with ovalbumin (ovalbumin group) or gliadin (gliadin group) with Freund's complete adjuvant. The cell-free DNA (cf-DNA) was quantified by using dsDNA quantification kit, while the levels of Immunoglobulins, complement C3 and myeloperoxidase-DNA (MPO-DNA) in serum were tested using enzyme linked immunosorbent assay (ELISA). The IgA, complement C3 and NETs in tissues were detected through multiple immunofluorescences. Both the ovalbumin group and gliadin group showed IgA and C3 deposition in various tissues, including the glomerular mesangial region, skin, and digestive tract, while the control group showed no such deposition. The levels of circulatory cf-DNA and MPO-DNA, which are components of NETs, were significantly elevated in both ovalbumin and gliadin groups compared with the control group. Furthermore, the presence of NETs were found in gastrointestinal and renal tissues of the ovalbumin and gliadin groups, but not in the control group. IgAV model rat can be established through the combination of ovalbumin and gliadin with Indian ink and Freund's complete adjuvant. This study provides the first confirmation that NETs are involved in the pathogenesis of IgAV rat.