Serum Levels Of Complement Components Research Articles

Efficacy of Qingying decoction and Wuling powder in the treatment of renal hematuria: A traditional Chinese medicine approach

Purpose: To investigate the efficacy of combining Qingying decoction with Wuling powder in the treatment of renal hematuria. Method: Seventy-six patients diagnosed with renal hematuria in the Emergency General Hospital and Nanmofang Community Health Service Center in Chaoyang District of Beijing, China were randomized equally into study and control groups. Control group received standard Western treatment in addition to Shenyan Rehabilitation tablets while study group received a combination of Qingying decoction and a modified Wuling powder alongside standard treatment for eight weeks. Treatment effectiveness was evaluated using urinary red blood cell count (URBC), urinary albumin-to-creatinine ratio (UACR), urinary β 2-microglobulin (β2-MG) and α 1-microglobulin (α1-MG) levels, serum levels of complement components 3 (C3) and 4 (C4), immunoglobulin A (IgA), and Traditional Chinese Medicine (TCM) syndrome scores. Results: There was a significant difference in total therapeutic effectiveness between study and control groups (p < 0.01). Study group showed significantly improved hematuria and total syndrome scores (p < 0.01). The study group showed significantly lower URBC, UACR, β 2-MG, α 1-MG, IgA, and C3 levels compared to the control group (p < 0.05). Conclusion: Treatment with Qingying decoction and Wuling powder demonstrates efficacy in managing renal hematuria, regulates urinary red blood cell counts, reduces symptoms, and lowers early renal impairment. Future studies in multiple centers using larger number of patients to determine the mechanisms of these drug actions and interactions and other related factors would be required.

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...

Systemic complement activation in anti-neutrophil cytoplasmic antibody-associated vasculitis and necrotizing glomerulonephritis.

Due to the accumulating evidence of complement activation in anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), we decided to investigate the possibility of systemic complement activation in patients with Necrotizing Glomerulonephritis secondary to AAV. Clinical, laboratory and histological findings, and serum levels of complement components, C3a, C5a and Bb fragment of Factor B and C4d, were estimated in patients with AAV and glomerulonephritis, at time of diagnosis, before any treatment had been applied. All patients were treated with the same immunosuppressive protocol and followed up for total 24 months. Twenty age and sex matched healthy individuals served as controls. Serum levels of all complement components were significantly increased in patients, compared to controls; C5a: 19.9(0.02-48) vs 9.06(2.1-16.3)pg/mL, P = .002, Bb: 7.3(0.02-31.4) vs 0.2(0.02-1.6)pg/mL, P < .0001, C3a: 4.7(0.4-7.2) vs 2.4(1.09-5)pg/mL, P = .05 and C4d: 11.6(0.07-70) vs 0.7(0.07-8.2)pg/mL, P = .001, respectively. There was strong correlation between serum Bb levels and eGFR and FFS2009 score at time of diagnosis (r = -.41, P = .002 and r = .41, P = .003 respectively). Also, serum Bb levels were increased in patients with severe interstitial infiltration (P = .04) and focal necrosis (P = .01) on renal biopsy. Serum Bb levels could also predict renal function outcome during the acute phase of disease, but not at the end of follow up. We provided strong evidence of systemic activation of complement alternative pathway in the development and progression of AAV and glomerulonephritis. Serum Bb seem to play a critical role in the induction, also predicting disease activity and outcome, yet activation of classical pathway cannot be excluded.

Ultrasensitive serum interferon-α quantification during SLE remission identifies patients at risk for relapse

ObjectivesMaintenance of remission has become central in the management of systemic lupus erythematosus (SLE). The importance of interferon-alpha (IFN-α) in the pathogenesis of SLE notwithstanding, its expression in remission has...

Blood Cell-Bound C4d as a Marker of Complement Activation in Patients With the Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a chronic and disabling condition characterized by recurrent thrombosis and miscarriages mediated by antibodies against phospholipid-binding proteins (aPL), such as beta2glycoprotein I (β2GPI). Complement is involved in APS animal models and complement deposits have been documented in placenta and thrombotic vessels despite normal serum levels. Analysis of circulating blood cells coated with C4d displays higher sensitivity than the conventional assays that measure soluble native complement components and their unstable activation products in systemic lupus erythematosus (SLE). As C4d-coated blood cell count has been reported to be more sensitive than serum levels of complement components and their activation products in systemic lupus erythematosus (SLE) patients, we decided to evaluate the percentage of C4d positive B lymphocytes (BC4d), erythrocytes (EC4d), and platelets (PC4d) in primary APS patients and asymptomatic aPL positive carriers as marker of complement activation in APS. We assessed by flow cytometry the percentages of BC4d, EC4d, and PC4d in primary APS (PAPS; n. 23), 8 asymptomatic aPL positive carriers, 11 APS-associated SLE (SAPS), 17 aPL positive SLE, 16 aPL negative SLE, 8 aPL negative patients with previous thrombosis, 11 immune thrombocytopenia (ITP) patients, and 26 healthy subjects. In addition, we used an in vitro model to evaluate the ability of a monoclonal anti-β2GPI antibody (MBB2) to bind to normal resting or activated platelets and fix complement. EC4d and PC4d percentages were significantly higher in PAPS and aPL carriers as well as aPL positive SLE and SAPS than in aPL negative controls. The highest values were found in PAPS and in SAPS. The EC4d and PC4d percentages were significantly correlated with serum C3/C4 and anti-β2GPI/anti-cardiolipin IgG. In vitro studies showed that MBB2 bound to activated platelets only and induced C4d deposition. The detection of the activation product C4d on circulating erythrocytes and platelets supports the role of complement activation in APS. Complement may represent a new therapeutic target for better treatment and prevention of disability of APS patients.

Complement Levels in Nigeria Patients with Sickle Cell Anaemia in the Asymptomatic State.

Significantly low serum levels of complement components have been reported in patients with Sickle cell anaemia (SCA) which may result in a high susceptibility to infections. However some studies have reported a normal or high complement level. The aim of our study was to assess some haematological parameters and Complement levels in adult patients with steady state SCA in Zaria, North western Nigeria. This will serve as a guide towards infection surveillance in the quest to reduce significant morbidity and mortality in our setting. A cross sectional study of 40 patients with SCA in steady state and 40 healthy (non-matched) non-SCA controls at the Haematology clinic of Ahmadu Bello University Teaching Hospital Zaria, was carried out over a 6 month period in 2016. Institutional ethical approval and informed written consentwere obtained. Venous blood was analyzed for haematological parameters by an automated method and complement levels; alternative pathway was assessed by measuring C3, classical pathway by C4 and Terminal pathways by C5 levels using ELISA technique. Data was analyzed with statistical package for social science(SPSS) software version 20.0(2001) and a p value of ≤ 0.05 was considered significant. The age range of patients with SCA and controls were 18 to 46years and 18 to 48years respectively and these were not significantly different p > 0.05. The median levels of C3 (245μg/ml), C4 (245μg/ml) and C5 (40μg/ml) were within normal range in the study subjects but significantly higher (p < 0.05), than those of the controls C3 (165μg/ml), C4 (125μg/ml) and C5(35μg/ml). Haematological parameters showed no correlation with the levels of Complement components studied. Although Complement components C3, C4, and C5 levels in patients with SCA are significantly high, the infectious susceptibility may be due to other immunological abnormalities.

Diagnostic value of progranulin in patients with lupus nephritis and its correlation with disease activity

The aim of this study was to explore whether progranulin (PGRN) can be a useful marker not only for accurate diagnosis of patients with active lupus nephritis (LN), but also for prediction of the disease activity in this population. A total of 154 LN patients were enrolled in this study, 76 of which were diagnosed as having active LN and 78 as having stable LN. Additionally, 71 age-matched non-LN patients were enrolled as controls. The serum and urine PGRN levels of each study population were measured using the enzyme-linked immunosorbent assay method. The diagnostic performance of both indicators and their correlation with the disease activity of LN were systematically investigated using receiver operating characteristic (ROC) analysis and correlation analysis. The active LN population had significantly higher serum and urine PGRN levels than the other two populations. ROC analysis further demonstrated that these two indicators, particularly in combination, appear to have a strong performance in discriminating active LN patients from the rest of the LN population. In the active LN population, serum and urine PGRN levels were not only significantly correlated with SLEDAI score, rSLEDAI score, and activity index, but also had a considerable association with several key markers reflecting the disease activity of LN, including serum levels of complement component 3 and ds-DNA. Nevertheless, neither of the two indicators were correlated with the pathological classification of LN, chronicity index, serum creatinine level, and 24-h urine protein levels. Our findings demonstrate that PGRN may have great potential as a diagnostic factor for active LN and as a predictor for its disease activity.

Complement Split Products C3a/C5a and Receptors: Are They Regulated by Circulating Angiotensin II Type 1 Receptor Autoantibody in Severe Preeclampsia?

Background: This study measured the serum levels of complement component (C)3a and C5a and the placental expressions of C3a receptor (R) and C5aR to determine a potential correlation with circulating angiotensin II type 1 (AT1) receptor agonistic autoantibody (AT1-AA) in severe pre-eclampsia. Methods: A total of 118 women were recruited and divided into 2 groups: the control group (normotensive preterm pregnancies, n = 66) and severe pre-eclampsia group (n = 52). Levels of C3a, C5a and AT1-AA in serum were measured by enzyme-linked immunosorbent assay and C3aR and C5aR in placenta by Western blotting. Results: Levels of C3a, C5a and AT1-AA in serum from the severe pre-eclampsia group were significantly higher than in controls (p < 0.05). Placental expression of C3aR and C5aR in the pre-eclampsia group was lower than that in controls (p < 0.05). There were significant positive correlations between levels of C3a, C5a and AT1-AA in serum from the pre-eclampsia group (p < 0.05). In contrast, there was no correlation between C3aR and C5aR in the placenta and AT1-AA in serum in the pre-eclampsia group (p > 0.05). Conclusion: Increased C3a, C5a and AT1-AA in the serum provide indirect evidence that AT1-AA-mediated activation contributes to activate complement, which is a key mechanism underlying the pathogenesis of severe pre-eclampsia.

Metabolic impact on serum levels of complement component 3 in Japanese patients

The aim of this study was to explore the association between the serum concentration of complement component 3 (C3) and a variety of metabolic parameters. The study involved 125 patients in our outpatient clinic. Anthropometric and clinical laboratory data were collected and statistical associations between the serum concentration of C3 and other parameters were evaluated in a cross-sectional as well as a prospective manner. A group of male patients with metabolic syndrome (Mets, n=35) were characterized by marked increase in serum concentrations of C3, body mass index (BMI), waist circumference, hemoglobin (Hb) A1c, insulin resistance (HOMA-IR), triglyceride, uric acid, urinary protein, and Hb. In a one-way analysis of variance of all subjects, the serum concentration of C3 was significantly elevated as the number of items of complying with the Mets diagnostic criteria increased. In 60 of 125 patients who did not have diabetes and were given anti-lipogenetic medication, the serum concentration of C3 showed significant positive associations with serum levels of CH50, insulin, HOMA-IR, total cholesterol, hematocrit, LDL-c, C4, Hb, triglyceride, BMI, and albumin. In a prospective follow-up evaluation (n=35), there was a significant positive association between DeltaC3 (the second concentration of serum C3 minus the first concentration of serum C3)and DeltaHOMA-IR (the second concentration of HOMA-IR minus the first concentration of HOMA-IR). In conclusion, in Japanese patients, there is evidence implicating C3 concentration as a marker of Mets coinciding with insulin resistance.

Hypercomplementemia in adult patients with IgA nephropathy

IgA nephropathy (IgAN) is the most common form of chronic glomerulonephritis. Although glomerular deposition of complement components is well known, the evidence of serological complement activation in IgAN is inconclusive. We hypothesized that serum levels of complement components and regulatory proteins in patients with IgAN are correlated with its pathogenesis. In the present study we measured complement components in 50 patients with IgAN and 50 healthy volunteers. C5, C1 inhibitor, factor B, C4 binding protein, factor H, and factor I were measured with the use of single radial immunodiffusion. Mannose-binding lectin (MBL) and properdin (P) were measured by enzyme-linked immunosorbent assay (ELISA). The correlations among complements in the sera of patients with clinical gradings for IgAN (i.e., the good prognosis group, relatively good prognosis group, relatively poor prognosis group, and poor prognosis group) were evaluated. CH50, C4, factor B, P, factor I, and factor H were significantly higher in IgAN patients than in healthy controls. There were significant correlations between C5 and C4 binding protein, between C3 and C5, or between C4 and factor B in patients with IgAN. In the poor prognosis group, C4 binding protein was significantly higher than in the other groups of IgAN patients. hypercomplementemia occurs in IgAN and is associated with an increase in complement regulatory protein (CRP). C4 binding protein analyses can be used to predict disease prognosis.

Effects of C-Reactive Protein and the Third and Fourth Components of Complement (C3 and C4) on Incidence of Atrial Fibrillation

Although C-reactive protein (CRP) is a major cardiovascular risk factor, its association with atrial fibrillation (AF) remains controversial. This study explored whether the CRP-related incidence of AF is modified by serum markers of inflammation in a population-based cohort with follow-up data. Serum CRP and 2 components of the complement system (C3 and C4) were determined in 1,011 healthy patients (25 to 64 years old). The incidence of AF was compared between groups defined by levels of CRP, C3, and C4. The follow-up time was 4 years. A high complement level was defined as either C3 or C4 in the top quartile. High CRP was associated with high complement components. An increased CRP level was associated with an increased incidence of AF. The complement components modified these associations. After risk factor adjustment, those with high CRP and high complement components had a significantly higher risk of AF (relative risk 3.0, 95% confidence interval 2.0 to 4.2) than those with normal CRP and low complement levels. In the absence of a high complement level, a high CRP level was not significantly associated with AF (relative risk 1.1, 95% confidence interval 1.0 to 1.4). In conclusion, high CRP levels are associated with high serum levels of complement components. These proteins increase the CRP-related incidence of AF. In the absence of elevated complement components, no statistically confirmed association was found between a high CRP level and AF.

Complement components (C3, C4) in childhood asthma.

To assess the involvement of complements (C3, C4) in the pathophysiology of bronchial asthma. Selection of patients (n = 64) were made according to the recommended international criteria for diagnosis and classification of asthma. Serum levels of complement components (C3, C4) were measured by radial immunodiffusion technique in 64 Libyan children (age: 1-12 years, sex: 39 males, 25 females) with mild to moderately severe asthma (Group A). Among these patients, 35 had active disease (AA) and 29 had inactive disease (NA). According to age range, 20, 21 and 23 patients were between 1-3 years (A1), > 3-5 years (A2) and > 5-12 years (A3) respectively. A1 had 9 and 11 patients with active (AA1) and inactive (NA1) disease; A2 had 10 and 11 patients with active (AA2) and inactive (NA2) disease; A3 had 16 and 7 patients with active (AA3) and inactive (NA3) disease respectively. Age matched comparisons were made with 57 healthy children (age: 1-12 years; sex: 30 males, 27 females) (Group B). Among the controls, 15, 19 and 23 children were between 1-3 years (B1), > 3-5 years (B2) and > 5-12 years (B3) respectively. Mean C3 level was significantly elevated in patients, while C4 level was normal (A vs B --> C3: P < 0.2, C4: P > 0.2). Serum C3 level was significantly higher in patients with active disease only, while it was normal in patients with inactive disease (AA, NA, B --> P = 0.045); AA vs NA --> P < 0.05, AA vs B --> P < 0.02, NA vs B --> P > 0.05) and C4 levels were normal in both the groups (AA, NA, B --> P = 0.354). Further, C3 levels were significantly elevated in all the age groups, but in patients with active disease only (AA1, NA1, B1 --> P = 0.0024; AA2, NA2, B2 --> P = 0.0411; AA3, NA3, B3 --> P = 0.0102). The elevated C3 level was possibly due to induction by pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). The probable mechanisms of C3 involvement in the pathophysiology of bronchial asthma were discussed.

Complement activation through the lectin pathway in patients with Henoch-Schönlein purpura nephritis

Henoch-Schönlein purpura nephritis (HSPN) is considered a form of systemic vasculitis of the small blood vessels with immune pathogenesis. In this disorder, the complement system is recognized as an important mechanism of glomerular injury. The aim of this study is to determine whether the lectin pathway, a novel pathway of complement activation, is related to the pathogenesis of HSPN. Renal biopsy material from 10 patients with HSPN was studied immunohistochemically and examined for a clinicopathologic correlation. Serum levels of complement components, including mannose-binding lectin (MBL), and plasma levels of complement activation products were also evaluated in these patients and compared with levels in patients with immunoglobulin A (IgA) nephropathy or mesangial proliferative glomerulonephritis (GN) without IgA deposition (non-IgA GN). Glomerular deposition of components of the pathway, MBL and MBL-associated serine protease (MASP-1), as well as C3b/C3c, C5b-9, and C4-binding protein (C4-bp), was detected in 8 of 10 patients. Although no significant correlation was found between glomerular deposition of MBL/MASP-1 and histological or clinical findings, the biopsies on all patients with MBL/MASP-1 deposits were performed within 20 weeks from the onset of disease. Levels of plasma C4d, the activation fragment of C4, and C4-bp, a soluble regulatory protein of the pathway, were greater in patients with HSPN than in those with non-IgA GN. However, there was no difference in serum MBL levels between the three groups of patients (HSPN, IgA nephropathy, and non-IgA GN). These results suggest that complement activation through the lectin pathway was involved at the onset of HSPN, and this mechanism might be important in the disease pathogenesis.

The efficacy of short-term danazol prophylaxis in hereditary angioedema patients undergoing maxillofacial and dental procedures

Purpose: This study evaluated the efficacy of short-term danazol prophylaxis in hereditary angioedema patients undergoing maxillofacial or dental procedures. Patients and Methods: Twelve patients with a history of edema after dental procedures were administered danazol (600 mg/d) 4 days preoperatively and 4 days postoperatively. The serum levels of complement components were determined preoperatively and postoperatively as well as at 6, 12 and 24 hours in six patients. Results: None of the 12 patients developed angioneurotic edema. The serum levels of the complement components were decreased immediately after surgery and returned to normal within 24 hours. Conclusion: The short-term prophylactic use of danazol in patients with hereditary angioedema undergoing oral surgery is an effective preventive measure.

Serum levels of complement components in patients with nasal hyperreactivity

Serum levels of complement components in patients with nasal hyperreactivity

The effect of anti-reactional drugs on complement components in the type II, erythema nodosum leprosum, reaction.

Seventeen patients with the type II (erythema nodosum leprosum) (ENL) reaction were studied. They received multidrug therapy and also the anti-reactional drugs prednisolone clofazimine or chloroquin, and we measured serum levels of complement components before treatment and after the reaction had subsided. Factor B was significantly elevated after treatment with each of the three drugs. C3 levels were significantly increased after treatment, the largest change being in patients treated with clofazimine. In these patients there was also a concomitant decrease in C3d levels. This suggests that clofazimine has complement modulating activity and we would recommend it as the drug of choice in treatment of the ENL reaction.

Predictive value of complement profiles and anti-dsDNA in systemic lupus erythematosus.

In a prospective study of 143 patients with systemic lupus erythematosus (SLE) the relation between clinical exacerbations, anti-dsDNA levels, and serum levels of complement components, C1q, C4, C3, C5, and C9 was investigated. In 33 out of these 143 patients a major clinical exacerbation of the disease developed. Evaluation of anti-dsDNA levels in relation to disease activity confirmed our earlier finding that anti-dsDNA levels rose before a major exacerbation and decreased after it. In the remaining 110 SLE patients a nearly constant anti-dsDNA level was seen, but none of these patients experienced a major exacerbation. In the 21 SLE patients who developed deterioration in renal function a decrease of C4 followed by decreases of C1q and C3 levels was seen first, starting about 25 to 20 weeks before the first signs of renal involvement. In the 12 SLE patients who developed an exacerbation without renal involvement an inconsistent profile of the complement components C4, C1q, and C3 was observed. C5 levels were hardly affected at all, while C9 levels were in general higher than normal during the exacerbation, irrespective of the type of exacerbation. These results show that, by following the complement and anti-dsDNA profiles, not only can exacerbations be predicted but also a pointer can be obtained about the pattern of disease well before the first clinical signs of an exacerbation appear.

Alterations of the complement and coagulation systems in meningo coccal infections: 84

Serum levels of complement components (C1q, C4, C3, C5, C9, C3PA and C1I), platelets, prothrombin time (PT), fibrinogen concentration and fibrin degradation products were measured at admission in 93 children (mean age 3.1±2.0 y)with meningococcal infections, 86% type B. Results were compared with an age matched normal group. Patients were classified in three groups: 21 with meningitis without systemic manifestations; 39 with uncomplicated septicemia and 33 with septicemia and shock. C1q was decreased (p<.001) in the three groups; C3 was also low but only in the last two groups was significantly diminished (p<.005). Forty-seven patients, regardless of the groups, showed a prolonged PT and 7 out of these 47 showed a disseminated intravascular coagulation. These 47 patients had lower levels of Clq (p<.02), C3 (p<.05), C5 (p<.05), C3PA (p<.005) when compared with the remaining patients with normal PT. Values of PT in all patients correlated well with the levels of C1q (p<.05), C4 (p<.01), C3 (p<.001), C5 (p<.001), C9 (p<.001) and C1I (p<.05). These results suggest that activation of the classical pathway of complement occurs in all patients with meningococcal infections, even in benign cases, and that such activation may be related to the alteration of the coagulation system.

691 IMMUNOCOMPETENCE IN OBESITY

Obese individuals are susceptible to respiratory and cutaneous infections and post-operative wound sepsis. In a group of 21 children and adolescents diagnosed to be obese on the basis of weight-for-height and skin-fold thickness, a comprehensive assessment of immunity function showed serum immunoglobulins within the normal range, slight elevation of serum IgE and adequate antibody response. Subpopulations of circulating lymphocytes were comparable in proportion and number in the obese and the non-obese. Cutaneous delayed hypersensitivity and mitogeninduced lymphocyte DNA synthesis were reduced, the latter particularly when autologous plasma was used in cell cultures. Serum levels of complement components, opsonization and phagocytosis were normal, but intracellular bacterial killing was impaired. In the obese group, the mean serum lipid concentration was higher, and transferrin saturation and zinc level lower than in the control group. It is suggested that alterations in the immunocompetence of obese individuals may in part be the result of changed nutritional milieu and that such changes may contribute to increased susceptibility to infection.

Clinical and experimental investigation of immune complexes in malaria

Aotus monkeys infected with quartan malaria ( Plasmodium brasilianum) and injected iv with radiolabeled anti- P. malariae IgG and/or normal IgG (no malarial antibodies) showed (a) increased in vivo binding of malarial antibodies into abnormally insoluble form when precipitated by 7.5% polyethylene glycol, (b) faster disappearance of this antibody from circulation, and (c) its increased deposition in renal glomeruli. Similar results were obtained in monkeys infected with P. falciparum and injected with anti- P. falciparum IgG but the difference against controls was much less pronounced. Serum levels of complement components (C3, C3-PA, and C4) rose after infection, and the highest levels coincided with peaks of parasitemia. Decrease to abnormally low levels was detected when antibody was produced. In Nigerian patients with nephrotic syndrome, results similar to the quartan malaria model in monkeys were found, i.e., increased binding of anti- P. malariae IgG with sera in vitro, its faster disappearance from circulation after iv injection, and increased deposition in kidney tissue IgG. These data indicate the binding of iv-injected specific antibody to soluble antigens and/or soluble immune complexes of excess antigen type (“ in vitro complexing”) and their increased depositions in kidney (glomerular) lesions. They also strengthen the important role of P. malariae in the pathogenesis of chronic progressive nephropathies occurring in malarial areas.