Inflammation underlies a wide variety of physiological and pathological processes, and plays a pivotal role in controlling pathogen infection. C1q/tumor necrosis factor (TNF) related proteins (CTRPs), a newly discovered adipokine family with conservative structure and wide distribution, has attracted increasing attention. The CTRP family consists of more than 15 members which fall into the characteristic C1q domain. Increasing studies have demonstrated that CTRPs are involved in the onset and development of inflammation and metabolism as well as related diseases, including myocardial infarction, sepsis and tumors. Here, we first clarified the characteristic domains of CTRPs, and then elucidated their roles in inflammatory-related diseases. Taken together, the information presented here provides new perspectives for therapeutic strategies to improve inflammatory and metabolic abnormalities.
Humans ; Complement C1q/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Inflammation/metabolism* ; Myocardial Infarction

OBJECTIVE: To investigate the risk factors of different types of Henoch-Schönlein purpura (HSP) in Tibetan patients at high altitude, as to provide reference for correctly identifying high-risk patients. METHODS: A retrospective study was used to analyze the 304 HSP patients admitted to Tibet Autonomous Region People's Hospital from April 2014 to March 2022. The gender, age, allergic history, family history, clinical type, laboratory indexes (hemoglobin, platelet count, eosinophil, C-reactive protein (CRP), albumin, immunoglobulin G, immunoglobulin A, complement C3 and C4) were analyzed retrospectively. Univariate and multivariate Logistic regression analysis to screen for risk factors affecting different types of HSP. RESULTS: Renal HSP patients showed higher IgA [(9.2±1.7) g/L <i>vs.i> (6.4±2.4) g/L, <i>Pi>=0.015], lower complement C3 [(203.3±21.6) mg/dL <i>vs.i> (301.1±19.5) mg/dL, <i>Pi>=0.043], and complement C4 [(33.5±2.3) mg/dL <i>vs.i> (53.0±7.2) mg/dL, <i>Pi>=0.032]. The patients with abdominal HSP showed lower levels of hemoglobin [(119.6±19.6) g/L <i>vs.i> (146.6±47.3) g/L, <i>Pi>=0.038] and plasma albumin [24.8 (22.1, 33.9) g/L <i>vs.i> 32.6 (24.6, 35.1) g/L, <i>Pi>=0.045]. The patients with articular HSP exhibited higher CRP [13.5 (0.2, 20.6) g/L <i>vs.i> 7.5 (0.1, 15.2) g/L, <i>Pi>=0.036] and erythrocyte sedimentation rate (ESR) [24 (5, 40) mm/h <i>vs.i> 15 (4, 30) mm/h, <i>Pi>=0.049]. Elevated IgA and decreased complement C4 were risk factors for renal HSP, anemia and decreased plasma albumin were risk factors for abdominal HSP, and elevated CRP was a risk factor for articular HSP. CONCLUSION The clinical characteristics of different types of HSP in plateau areas were different. Patients with high IgA, low complement C4, anemia, hypoalbuminemia, and significantly elevated CRP should be highly vigilant. Early and effective intervention can improve the clinical efficacy, avoid severe development, and improve the prognosis.
Humans ; Retrospective Studies ; Tibet/epidemiology* ; Complement C3/analysis* ; IgA Vasculitis/complications* ; Altitude ; Complement C4 ; C-Reactive Protein/analysis* ; Immunoglobulin A ; Risk Factors ; Anemia ; Hemoglobins/analysis* ; Serum Albumin/analysis*

OBJECTIVE: To analyze the change of serum C1q in the course of multiple myeloma (MM) and its correlation with clinical characteristics. METHODS: 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. RESULTS: 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). CONCLUSION 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.
Albumins ; Bone Marrow ; Complement C1q ; Humans ; Multiple Myeloma ; Risk Factors

Hemolytic uremic syndrome (HUS) is clinically rare, with high mortality and case fatality rates. In recent years, the research on HUS has been intensified and the pathophysiological mechanism has been continuously improved. At present, the main mechanism of pathogenesis is the excessive activation of complement alternative pathways mediated by complement-related gene mutations or the existence of antibodies. The treatment methods and strategies are also constantly updated, mainly including complement-blocking drugs such as Eculizumab, Lavalizumab, and Ravulizumab. In this review, the new developments in the pathogenesis and treatment of HUS is summarized, and provide references for the clinical treatment of HUS.
Complement System Proteins/therapeutic use* ; Hemolytic-Uremic Syndrome/therapy* ; Humans ; Mutation

Therapeutic dentin regeneration remains difficult to achieve, and a majority of the attention has been given to anabolic strategies to promote dentinogenesis directly, whereas, the available literature is insufficient to understand the role of inflammation and inflammatory complement system on dentinogenesis. The aim of this study is to determine the role of complement C5a receptor (C5aR) in regulating dental pulp stem cells (DPSCs) differentiation and in vivo dentin regeneration. Human DPSCs were subjected to odontogenic differentiation in osteogenic media treated with the C5aR agonist and C5aR antagonist. In vivo dentin formation was evaluated using the dentin injury/pulp-capping model of the C5a-deficient and wild-type mice. In vitro results demonstrate that C5aR inhibition caused a substantial reduction in odontogenic DPSCs differentiation markers such as DMP-1 and DSPP, while the C5aR activation increased these key odontogenic genes compared to control. A reparative dentin formation using the C5a-deficient mice shows that dentin regeneration is significantly reduced in the C5a-deficient mice. These data suggest a positive role of C5aR in the odontogenic DPSCs differentiation and tertiary/reparative dentin formation. This study addresses a novel regulatory pathway and a therapeutic approach for improving the efficiency of dentin regeneration in affected teeth.
Animals ; Cell Differentiation/physiology* ; Cells, Cultured ; Complement C5a/metabolism* ; Dental Pulp/physiology* ; Dentin ; Mice ; Receptor, Anaphylatoxin C5a ; Stem Cells

Objective:b> To assess the correlation of glomerular C1q or IgA deposition with clinical and pathological features of primary membranous nephropathy (PMN) in children. Methods:b> The clinical and pathological manifestations including (phospholipase A2 receptor, PLA2R) and IgG subclasses staining in renal biopsies, serum anti-PLA2R antibody and therapeutic response of 33 children diagnosed with PMN in Peking University First Hospital from December 2012 to December 2020 were retrospectively summarized and analyzed. According to results of PLA2R test and findings renal pathological, the patients were divided into PLA2R-related group and non-PLA2R-related group, typical MN group and atypical MN group, C1q deposit group and non-C1q deposit group, as well as IgA deposit group and non-IgA deposit group respectively. T-test, Mann-Whitney <i>Ui> test and Fisher's exact probability test were used for comparison between the groups. Results:b> Among the 33 children with PMN, there were 20 males and 13 females, of that the age of onset was 11 (8, 13) years, and 32 patients had nephrotic level proteinuria. Renal biopsies were performed at 4.6 (2.1, 11.6) months after onset, and 28 patients (85%) received glucocorticoid or immunosuppressive therapy prior to renal biopsy. There were 20 cases (61%) with PLA2R-related MN and 13 cases (39%) with non-PLA2R-related MN. Compared with the non-PLA2R-related group, the PLA2R-related group had an older age of onset (12 (10, 13) <i>vs.i> 7 (3, 12) years, <i>Z=-i>2.52, <i>P=i>0.011), a lower preceding infection rate (45% (9/20) <i>vsi>. 11/13, <i>P=i>0.032) and lower spontaneous remission rate (0 <i>vsi>. 4/13, <i>P=i>0.017). Renal PLA2R positivity was significantly associated with predominant or co-deposition of IgG4 (13/17 <i>vs.i> 5/15, <i>Pi>=0.031) and low albumin levels at renal biopsy ((25±6) <i>vs.i> (29±7) g/L, <i>t=i>2.14, <i>P=i>0.041). There were 12 patients with typical PMN and 21 patients with atypical PMN, and no significant difference in clinical and pathological manifestations was found between these 2 groups (all <i>Pi>>0.05). There were 10 cases (32.3%) with glomerular C1q deposition, and their disease course before renal biopsy was significantly shorter than those without C1q deposition (1.8 (0.8, 5.9) <i>vs.i> 6.0 (2.5, 22.3) months, <i>Z=-i>2.27, <i>P=i>0.023). Twelve cases (36.4%) had glomerular IgA deposition, and their course of disease,clinical and pathological manifestations were not significantly different from those without IgA deposition (all <i>Pi>>0.05). Conclusion:b> Glomerular C1q or IgA deposition may not affect the clinical manifestations, glomerular PLA2R and IgG subclasses staining pattern, or the response to treatment of PMN in children.
Autoantibodies ; Child ; Complement C1q/metabolism* ; Female ; Glomerulonephritis, Membranous/drug therapy* ; Humans ; Immunoglobulin A/immunology* ; Immunoglobulin G ; Kidney Glomerulus ; Male ; Retrospective Studies

To study the interaction between C4b-binding protein (C4BP) and Riemerella anatipestifer (RA), we cloned duck C4BPα, conducted prokaryotic expression and prepared the polyclonal antibody by immunizing mice. Then indirect immunofluorescence assay and dot blotting hybridization assay were used to verify the interaction between C4BP and RA. The full length of duck C4BPα nucleotide sequence was 1 230 bp, with the highest similarity to chicken C4BPα (82.1%). Phylogenetic tree analysis showed that duck C4BPα and chicken C4BPα were on the same phylogenetic tree branch and the genetic evolution relationship between them was the closest. C4BPα was efficiently expressed in Escherichia coli BL21 (DE3). The recombinant proteins existed in intracellular soluble form. The titer of polyclonal antibody was more than 1:10 000 and polyclonal antibodies could specifically recognize the recombinant proteins. The results of indirect immunofluorescence assay and dot blot hybridization assay showed that RA could interact with duck C4BP. The results provide a basis to further reveal the pathogenesis of RA.
Animals ; Cloning, Molecular ; Complement C4b-Binding Protein ; chemistry ; genetics ; metabolism ; Ducks ; classification ; genetics ; microbiology ; Gene Expression Regulation ; Mice ; Phylogeny ; Riemerella ; metabolism

OBJECTIVE: To study the expression and diagnostic value of plasma miR-145 and miR-183 in children with lupus nephritis (LN). METHODS: A total of 92 children with LN who were admitted from January 2016 to May 2019 were enrolled as the LN group, among whom 17 had type II LN, 15 had type III LN, 36 had type IV LN, 18 had type V LN, and 6 had type VI LN. Forty healthy children who underwent physical examination were enrolled as the healthy control group. According to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the 92 children with LN were further divided into a stable LN group with 34 children (SLEDAI score <10) and an active LN group with 58 children (SLEDAI score ≥10). RT-PCR was used to measure the expression of miR-145 and miR-183 in plasma. The receiver operating characteristic (ROC) curve was used to analyze the value of plasma miR-145, miR-183, and anti-dsDNA antibody in the diagnosis of LN. Pearson correlation analysis was used to investigate the correlation of the expression levels of miR-145 and miR-183 in plasma with laboratory markers. RESULTS: The LN, active LN, and stable LN groups had significantly higher levels of anti-dsDNA antibody, C-reactive protein, serum creatinine (Scr), and blood urea nitrogen (BUN) than the control group (P<0.05). The active LN group had significantly higher SLEDAI score, anti-dsDNA antibody, Scr, and BUN than the stable LN group (P<0.05). The LN, active LN, and stable LN groups had significantly lower levels of complement C3, complement C4, and serum albumin (Alb) than the control group (P<0.05). The active LN group had a significantly lower level of Alb than the stable LN group (P<0.05). The LN, active LN, and stable LN groups had significantly lower plasma levels of miR-145 and miR-183 than the control group (P<0.01). The active LN group had significantly lower plasma levels of miR-145 and miR-183 than the stable LN group (P<0.01). The children with difference types of LN had significantly lower plasma levels of miR-145 and miR-183 than the control group (P<0.01), and the type V-VI group and the type IV group had significantly lower plasma levels of miR-145 and miR-183 than the type II-III group (P<0.01). The ROC curve analysis showed that the optimal cut-off values of plasma miR-145, miR-183, and anti-dsDNA antibody were 1.05, 0.62, and 186.30 IU/mL respectively, in the diagnosis of LN, and the combination of these three indices had the largest area under the ROC curve of 0.896 (95%CI: 0.835-0.955), with a sensitivity of 90.5% and a specificity of 84.2%. In the children with LN, the plasma levels of miR-145 and miR-183 were negatively correlated with SLEDAI score, anti-dsDNA antibody, Scr, and BUN (P<0.05) and were positively correlated with complement C3, complement C4, and Alb (P<0.05). CONCLUSIONS There are significant reductions in the expression levels of miR-145 and miR-183 in plasma in children with LN, which are correlated with the activity level and pathological typing of LN. Combined measurement of miR-145, miR-183, and anti-dsDNA antibody has a high value in the diagnosis of LN.
Biomarkers ; Child ; Complement C4 ; Humans ; Lupus Nephritis ; genetics ; MicroRNAs ; genetics ; ROC Curve

BACKGROUND: We aimed to investigate whether various immune-related plasma proteins, alone or in combination with conventional clinical risk factors, can predict spontaneous preterm delivery (SPTD) and intra-amniotic infection in women with premature cervical dilation or a short cervix (≤ 25 mm).METHODS: This retrospective study included 80 asymptomatic women with premature cervical dilation (n = 50) or a short cervix (n = 30), who underwent amniocentesis at 17–29 weeks. Amniotic fluid (AF) was cultured, and maternal plasma was assayed for interleukin (IL)-6, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and complements C3a and C5a, using enzyme-linked immunosorbent assay (ELISA) kits. The primary outcome measures were SPTD at < 32 weeks and positive AF cultures.RESULTS: The plasma levels of IL-6, C3a, and C5a, but not of MMP-9 and TIMP-1, were significantly higher in women with SPTD at < 32 weeks than in those who delivered at ≥ 32 weeks. The women who delivered at < 32 weeks had more advanced cervical dilatation, and higher rates of antibiotic and tocolytic administration and were less likely to be given vaginal progesterone than those who delivered at ≥ 32 weeks. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma IL-6 and C3a levels, and cervical dilatation (area under the curve [AUC], 0.901). The AUC for this model was significantly greater than that for any single variable included in the predictive model. In the univariate analysis, plasma IL-6 level was the only significant predictor of intra-amniotic infection.CONCLUSION: In women with premature cervical dilation or a short cervix, maternal plasma IL-6, C3a, and C5a levels could be useful non-invasive predictors of SPTD at < 32 weeks. A combination of these biomarkers and conventional clinical factors may clearly improve the predictability for SPTD, as compared with the biomarkers alone. An increased plasma level of IL-6 predicted intra-amniotic infection.
Amniocentesis ; Amniotic Fluid ; Area Under Curve ; Biomarkers ; Blood Proteins ; Cervix Uteri ; Complement System Proteins ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-6 ; Interleukins ; Labor Stage, First ; Outcome Assessment (Health Care) ; Plasma ; Pregnancy ; Progesterone ; Retrospective Studies ; Risk Factors ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinases

BACKGROUND AND OBJECTIVES: Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL.METHODS: HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio.RESULTS: After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories.CONCLUSIONS: In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.
Amyloid ; Angiotensinogen ; Atherosclerosis ; Cardiovascular Diseases ; Cholesterol ; Complement System Proteins ; Immunoglobulin mu-Chains ; Lipoproteins ; Nitric Oxide ; Plasma ; Proteomics ; Serine Proteases ; Thyroxine-Binding Globulin ; Vascular Cell Adhesion Molecule-1 ; Vitronectin