Plasma Levels Of Complement Factor Research Articles

Indices of complement activation and coagulation changes in trauma patients

ObjectivesEarly complementopathy and coagulopathy are shown often after trauma. However, the prevalence of any interplay between complement cascade (ComC) and coagulation cascade (CoaC) after trauma remains unclear. This study intended...

Complement Factor H as a potential atherogenic marker in chronic Chagas' disease.

We aimed to investigate the association between plasma levels of complement Factor H (FH) with cardiac involvement, inflammatory and cardiometabolic parameters in patients with chronic Chagas' disease (CD). FH plasmatic levels were determined in 80 chronic CD patients. Glycaemic index, lipidogram (high-density lipoprotein cholesterol HDL-C, low-density lipoprotein cholesterol LDL-C, triglycerides and total cholesterol) and Ultrasensitive C-Reactive Protein (uCRP) values were obtained from medical records. Height, weight, body mass index (BMI) blood pressure and left ventricular ejection fraction (LVEF) were obtained from echocardiography examinations. Comparisons between chronic CD clinical forms were performed using Mann-Whitney test and correlation Spearman's test. FH levels were correlated positively with triglycerides (P=.001, r=.39), LDL-C (P=.009, r=.3), cholesterol (P=.02, r=.28), uCRP (P=.029, r=.31) and BMI (P=.008, r=.34); and negatively with HDL-C (P=.03, r=-.25) levels. Dyslipidemic patients showed higher FH levels compared to normolipidemic, although no difference for FH levels was observed between chronic CD clinical forms. Alternative pathway of complement may be a link between immune response and metabolic disorders, with important immunoregulatory role in chronic CD.

Complement Factor H Inhibits Anti-Neutrophil Cytoplasmic Autoantibody-Induced Neutrophil Activation by Interacting With Neutrophils.

Our previous study demonstrated that plasma levels of complement factor H (FH) were inversely associated with the disease activity of patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). In addition to serving as an inhibitor of the alternative complement pathway, there is increasing evidence demonstrating direct regulatory roles of FH on several cell types. Here, we investigated the role of FH in the process of ANCA-mediated activation of neutrophils and neutrophil–endothelium interaction. We demonstrated that FH bound to neutrophils by immunostaining and flow cytometry. Interestingly, ANCA-induced activation of neutrophils, including respiratory burst and degranulation, was inhibited by FH. Although FH enhanced neutrophils adhesion and migration toward human glomerular endothelial cells (hGEnCs), it inhibited ANCA-induced activation of neutrophils in the coculture system of hGEnCs and neutrophils. Moreover, the activation and injury of hGEnCs, reflected by the level of endothelin-1 in the supernatant of cocultures, was markedly reduced by FH. However, we found that FH from patients with active AAV exhibited a deficient ability in binding neutrophils and inhibiting ANCA-induced neutrophil activation in fluid phase and on endothelial cells, as compared with that from healthy controls. Therefore, our findings indicate a novel role of FH in inhibiting ANCA-induced neutrophil activation and protecting against glomerular endothelial injury. However, FH from patients with active AAV are deficient in their ability to bind neutrophils and inhibit neutrophil activation by ANCA. It further extends the current understanding of the pathogenesis of AAV, thus providing potential clues for intervention strategies.

Plasma Levels of Complement Factor I and C4b Peptides Are Associated with HIV Suppression.

Individuals who exhibit long-term HIV suppression and CD4 T-cell preservation without antiretroviral therapy are of great interest for HIV research. There is currently no robust method for rapid identification of these “HIV controller” subjects; however, HLA-B*57 (human leukocyte antigen (major histocompatibility complex), class I, B*57) genotype exhibits modest sensitivity for this phenotype. Complement C3b and C4b can influence HIV infection and replication, but studies have not examined their possible link to HIV controller status. We analyzed HLA-B*57 genotype and complement levels in HIV-positive patients receiving suppressive antiretroviral therapy, untreated HIV controllers, and HIV-negative subjects to identify factors associated with HIV controller status. Our results revealed that the plasma levels of three C4b-derived peptides and complement factor I outperformed all other assayed biomarkers for HIV controller identification, although we could not analyze the predictive value of biomarker combinations with the current sample size. We believe this rapid screening approach may prove useful for improved identification of HIV controllers.

Complement factor H levels in steady state sickle cell anaemia

Objective : The red cell membrane of sickle cell anaemia is vulnerable to attack from the alternative complement pathway. The activation of the alternative complement pathway is initiated by externalization of phosphatidylserine on red cell membrane. Serum and cell bound regulators normally prevent amplification of the cascade. However, red blood cells in sickle cell anaemia appear to be exposed and the cell lysing membrane attack complex is ubiquitous on irreversible sickle red blood cells. It is possible that there are deficiencies (either functional or quantitative) of complement regulators. In this study the quantitative defects of the most abundant serum phase regulator, complement factor H in sickle cell anaemia was investigated. Methods : We compared the plasma levels of complement factor H (a serum phase regulator of the alternative pathway) in 61 steady state Hb SS with 60 healthy Hb AA using an enzyme linked immunosorbent assay to analyze complement factor H level in the plasma. The full blood count parameters were estimated using flow cytometry. Results : There was no significant difference in the serum complement factor H levels between the steady state Hb SS and healthy Hb AA. Significant inverse relationships existed between complement factor H, total white cell count, granulocyte cell count and platelet count as well as significant direct relationships between complement factor H, haematocrit, and the haemoglobin concentration. Conclusion : Complement factor H in patients with sickle cell anaemia who are in steady state is not significantly lower than in controls. Keywords : Complement factor H, sickle cell anaemia, alternative pathway

Maternal plasma levels of complement Factor H in miscarriage and in normal pregnancy: A cohort study

The incidence of clinically recognizable miscarriage in general population is up to 15%. It has been shown that complement Factor H (CFH) mRNA levels were increased in endometrium of women during early pregnancy, compared to non-pregnant women. We hypothesized that patients with miscarriage could have lower protein levels of CFH. The objectives of this prospective cohort is to measure plasma levels of Factor H in pregnancies up to 20 weeks, and to investigated whether there is an association between CFH and miscarriage. Plasma levels of CFH were measured in a cohort of pregnant women, ranging from 3 to 19.6 weeks who attended a gynecologic emergency unit in Brazil. Subjects had a blood sample obtained at the first consultation and were followed up to 24 weeks. After reaching outcome, subjects were divided into 4 groups: (1) miscarriage at entry the study, (2) normal pregnancy, (3) those that evolved to miscarriage, and (4) a control group of 6 non-pregnant, fertile proven women. Kruskal–Wallis test was used for statistical analysis. From 193 eligible women, 4 were excluded due technical problems and 33 were lost to follow-up. Median levels (range) of CFH were 989.2μg/mL (372–1644) n=64; 1042μg/mL (600.7–1915) n=74; 1089μg/mL (813.7–1250) n=12; 1004μg/mL (901.7–1335) n=6 in groups 1–3 and control, respectively; p=0.46—Kruskal–Wallis; post-hoc power (1-β)=31.6%. Therefore, median plasma levels of CFH are not different between women with miscarriage or normal pregnancy up to 19.6 weeks.

Abstract T P395: Complement Activation in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage - An Autopsy Study

Background: The pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. It has been hypothesized that an inflammatory response in the subarachnoid space and microthrombosis contribute to DCI. Previous studies showed that plasma levels of complement factors are associated with DCI and functional outcome after aSAH. We performed an autopsy study to investigate the relationship between complement activation, microthrombosis and DCI. Methods: In autopsy material from 7 patients who died from DCI, we isolated 9 areas of cerebral infarction and 15 areas without infarction. From autopsy material of 5 controls (myocardial infarction: n=3; heart failure: n=1; pulmonary embolism: n=1) we isolated 15 corresponding areas. We performed immunohistochemistry to investigate the presence of C1q, C3c, and fibrin(ogen) (which is strongly correlated with microthrombosis). Optical density measurements were used for quantitative assessments. Optical density values were compared between areas with infarction, without infarction, and controls, and analyzed with a Mann-Whitney U test. Spearman correlation tests were performed to investigate the relationships of C1q and C3c with fibrin(ogen). Results: Optical density values of C1q, C3c, and fibrin(ogen) were higher in areas of infarction than in areas without infarction or controls (Table 1, p<0.001 for all comparisons). Correlations were found between C1q and fibrin(ogen) (r=0.73, p<0.001) and C3c with fibrin(ogen) (r=0.74, p<0.001). Conclusion: Our results show that areas of cerebral infarction in patients with aSAH have more complement activation and microthrombosis than areas without infarction or control brains. A strong correlation was found between complement activation and microthrombosis. Future studies are needed to investigate if drugs targeting complement activation decrease the risk of DCI and improve outcome after aSAH.

The Effect of Lutein Supplementation on Blood Plasma Levels of Complement Factor D, C5a and C3d

Lutein is selectively taken up by the primate retina and plays an important role as a filter for harmful blue light and as an antioxidant. Recent studies have shown that lutein has systemic anti-inflammatory properties. Dietary lutein has been associated with reduced circulating levels of inflammatory biomarkers such as CRP and sICAM. Whether lutein also affects activation of the complement system has not yet been addressed and was the purpose of the study described here. Seventy-two subjects with signs of early macular degeneration were randomly assigned to receive either a 10 mg lutein supplement or a placebo during one year. EDTA blood samples were collected at 0, 4, 8 and 12 months. Complement factor D (CFD), a rate limiting component of the alternative pathway of complement activation and the complement activation products C5a and C3d were determined in the plasma samples by ELISA. A significant 0.11 µg/ml monthly decrease in plasma CFD concentration was observed in the lutein group (p<0.001), resulting in a 51% decrease from 2.3 µg/ml at baseline to 1.0 µg/ml at 12 months. The C5a concentration showed a significant 0.063ng/ml monthly decrease in the lutein group (p<0.001) resulting in a 36% decrease from 2.2ng/ml at baseline to 1.6ng/ml at 12 months. The C3d concentration showed a significant 0.19µg/ml monthly decrease in the lutein group (p=0.004) that gave rise to a 9% decrease from 15.4µg/ml at baseline to 14.4µg/ml at 12 months. In the placebo group we found a significant 0.04 µg/ml monthly decrease in plasma CFD concentration, whereas no changes were observed for C5a and C3d. Lutein supplementation markedly decreases circulating levels of the complement factors CFD, C5a and C3d levels, which might allow a simple method to control this inflammatory pathway of the innate immune system.

Plasma levels of complement C3 is associated with development of hypertension: a longitudinal cohort study

Hypertension has been associated with raised plasma levels of complement factor 3 and 4 (C3 and C4). The nature of this association is unclear. This population-based longitudinal study explored whether C3 or C4 is associated with development of hypertension. Blood pressure and plasma levels of C3 and C4 were determined in 2178 healthy men, aged 35-50 years, initially without treatment for hypertension. Incidence of hypertension and blood pressure increase over 15.7 (+/-2.2) years follow-up was studied in relation to C3 and C4 at baseline. Among men with initially normal blood pressure (<160/95 mm Hg), incidence of hypertension (>or=160/95 mm Hg or treatment) was 32, 42, 37 and 47%, respectively, for men with C3 in the first, second, third and fourth quartile (trend: P=0.001). This relationship remained significant after adjustment for confounding factors. Among men without blood pressure treatment, systolic BP increase (mean+standard error, adjusted for age, initial blood pressure and follow-up time) was 17.5+0.8, 19.6+0.9, 19.8+0.8 and 20.8+0.8 mm Hg, respectively, in the C3 quartiles (trend: P=0.004). C3 was not associated diastolic blood pressure at follow-up. Although C4 was associated with blood pressure at the baseline examination, there was no relationship between C4 and development of hypertension or future blood pressure increase. It is concluded that C3 in plasma is associated with future blood pressure increase and development of hypertension.

Weight gain in relation to plasma levels of complement factor 3: results from a population-based cohort study

Mice that are deficient for complement factor 3 (C3) have shown resistance to weight gain, despite increased food intake. Cross-sectional studies of humans have reported correlations between C3 and obesity. This longitudinal study explored whether C3 predicts a large weight gain in middle-aged men. Plasma concentrations of C3 and complement factor 4 (C4) were measured in 2,706 non-diabetic healthy men aged between 38 and 50 years, who were re-examined after a mean period of 6.1 years. After adjustments for initial weight, age, height and follow-up time, the odds of incurring large weight gain (75th percentile, > or =3.8 kg) were 1.00 (reference), 0.96 (95% CI:0.7-1.2), 1.1 (CI:0.9-1.5) and 1.4 (CI:1.1-1.8), respectively, among men with C3 levels in the first, second, third and fourth quartiles (p for trend=0.01) respectively. This relationship remained significant after further adjustments for lifestyle factors (physical inactivity, alcohol, smoking), metabolic factors (glucose or homeostasis model assessment values, cholesterol, triglycerides), inflammatory markers (fibrinogen, haptoglobin, ceruloplasmin, orosomucoid, alpha1-antitrypsin) and for C4. C4 was associated with weight gain after adjustments for initial weight, height, follow-up time and lifestyle factors, but not after adjustments for C3. C3 is a risk factor for incurring large weight gain in middle-aged men.

Factor H and the pathogenesis of renal diseases.

Complement factor H is a potent inhibitor of alternative pathway complement activation. The factor H gene, a member of the regulators of complement activation (RCA) gene cluster, encodes two plasma proteins, one 150 kilodaltons (kDa) and one 43 kDa. Homozygous deficiency of factor H results in low plasma levels of complement factor B and C3 and depletion of the terminal complement proteins C5-C9; heterozygotes may have reduced or normal levels of factor B, C3, and C5-C9. Although factor H deficiency is infrequently reported, it has been associated with a number of types of renal disease, the most common being atypical membranoproliferative glomerulonephritis and idiopathic (non-diarrhea-associated) hemolytic uremic syndrome (HUS). The molecular defects responsible for factor H deficiency have been described in only two cases; clearly more research is needed in this area. The possible role of factor H deficiency or dysfunction in the pathogenesis of HUS is discussed.

Lowering plasma levels of complement factor D with AN69 dialysis membranes.

Lowering plasma levels of complement factor D with AN69 dialysis membranes.

Lowering plasma levels of complement factor D with AN69 dialysis membranes

Lowering plasma levels of complement factor D with AN69 dialysis membranes

Lowering plasma levels of complement factor D with AN69 dialysis membranes

Lowering plasma levels of complement factor D with AN69 dialysis membranes

Detection of renal allograft rejection by complement components C5A and TCC in plasma and urine

Allograft rejection is associated with complement activation. Yet inconsistent results were obtained in evaluating plasma levels of complement factors or activation products as rejection markers. Therefore the human anaphylatoxin C5a and the soluble terminal complement complex (TCC) were measured by daily enzyme immunoassays on plasma (P) and urine (U) samples from 28 patients undergoing renal transplantation over a mean postoperative period of 25.8 days. The complement levels were evaluated longitudinally (cutoff of 100% increase on the previous day's level) during periods of rejection, stable graft function, acute tubular necrosis, and cytomegalovirus disease. Regarding the detection of 13 acute rejection episodes, U-C5a showed a diagnostic accuracy of 81% (sensitivity of 85%, specificity of 77%), P-C5a one of 62%, and P-TCC one of only 30%. The U-C5a increment (mean rise of 379%) preceded the clinical diagnosis of rejection by an average of 1.6 days. Cytomegalovirus diseases ( n = 4) were associated with high P-C5a levels (mean increase of 251% by the time of the first detection of viral DNA). In contrast, resumption of kidney function after acute tubular necrosis ( n = 10 periods) was heralded by marked peaks of U-C5a (x̄ = 43.7 μg/l). U-TCC was not detected in any clinical setting. In conclusion, as opposed to P-TCC, U-TCC, and P-C5a, the anaphylatoxin C5a, measured daily in urine, might have potential as an early and reliable marker for acute renal allograft rejection.

Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid carriers and complement factors induced by oral contraceptives

Three low-dose oral contraceptives Trinordiol ®, Gynatrol ®, and Marvelon ®, containing ethinylestradiol (EE) in combination with triphasic levonorgestrel (LNg), monophasic levonorgestrel, and monophasic desogestrel (DSG), respectively, were given to 65 healthy women, n = 21–22 in each group. Blood levels of antithrombin III (AT III), α 2-macroglobulin ( α 2M) α1-antitrypsin ( α 1at), complement factors (factor B, C3, C4), pregnancy zone protein (PZP), corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG) and albumin were measured before treatment and during the first and third treatment cycles. AT III levels decreased and α 1at levels increased in all three groups during treatment. α 2M increased during cycle 3 in the Trinordiol and Gynatrol groups. CBG, PZP and SHBG levels increased in all 3 groups, the CBG and PZP increase being higher in the Marvelon group than in the Gynatrol group. Increases in SHBG levels were found in the order Marvelon > Trinordiol > Gynatrol. Plasma levels of complement factors B, C3 and C4 remained unchanged. It is concluded that the increase in α 1at partly compensates for the fall in AT III, that the rise in PZP presumably enhances fibrinolysis, and that LNg has higher anti-estrogenicity and androgenicity than DSG.

Specific plasma proteins as indices of inflammation during a modified fast in patients with rheumatoid arthritis.

Fourteen patients with classical rheumatoid arthritis and 7 healthy controls underwent a modified fast, containing diluted fruit and vegetable juices, for a 10-day period. To evaluate the effect of fasting on the inflammatory activity, plasma protein determinations were performed before and on the 10th day of fasting. Both patients and healthy controls developed reduced plasma levels of complement factor 3 (C3), orosomucoid and haptoglobin, although only the decrease in C3 and orosomucoid was greater in the patient group. An unchanged level in plasma of albumin, IgG, IgA, IgM and complement factor 4 was found. We conclude that determination of C3 and orosomucoid in plasma may be useful as indices of inflammation during fasting conditions.

Polymorphonuclear Function in Patients with Skin and Joint Symptoms after Small-Intestinal Shunt Operations

Previous studies have shown that the small-bowel shunt operation for morbid obesity may be followed by signs of enhanced cell-mediated immunity and polymorphonuclear (PMN) granulocyte bactericidal capacity. In the present study seven patients, operated 4 months--4.5 years previously and exhibiting postoperative arthralgias, arthritis, and/or skin rashes, were investigated with regard to their PMN adherence and bactericidal capacity and plasma levels of complement factors 3 and 4 (C3 and C4). There patients showed a decreased PMN bactericidal capacity compared both with 10 other shunt-operated patients without skin and joint symptoms and with healthy controls, whereas PMN adherence was lower than for the non-symptomatic patients but similar to that of the controls. Two patients had C3 levels above the reference value; all had normal C4 values. Thus, a small-bowel shunt operation for obesity, complicated by skin and joint symptoms, might be associated with decreased PMN bactericidal capacity.

Plasma levels of complement factors 3 and 4, orosomucoid and opsonic functions in anorexia nervosa.

Acta PaediatricaVolume 68, Issue 5 p. 617-618 PLASMA LEVELS OF COMPLEMENT FACTORS 3 AND 4, OROSOMUCOID AND OPSONIC FUNCTIONS IN ANOREXIA NERVOSA J. Palmblad, J. Palmblad Department of Medicine IV Karolinska Institutet Södersjukhuset S-100 64 Stockholm 38 SwedenSearch for more papers by this authorLars Fohlin, Lars Fohlin Department of Medicine IV Karolinska Institutet Södersjukhuset S-100 64 Stockholm 38 SwedenSearch for more papers by this authorRenée Norberg, Renée Norberg Department of Medicine IV Karolinska Institutet Södersjukhuset S-100 64 Stockholm 38 SwedenSearch for more papers by this author J. Palmblad, J. Palmblad Department of Medicine IV Karolinska Institutet Södersjukhuset S-100 64 Stockholm 38 SwedenSearch for more papers by this authorLars Fohlin, Lars Fohlin Department of Medicine IV Karolinska Institutet Södersjukhuset S-100 64 Stockholm 38 SwedenSearch for more papers by this authorRenée Norberg, Renée Norberg Department of Medicine IV Karolinska Institutet Södersjukhuset S-100 64 Stockholm 38 SwedenSearch for more papers by this author First published: September 1979 https://doi.org/10.1111/j.1651-2227.1979.tb05067.xCitations: 9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume68, Issue5September 1979Pages 617-618 RelatedInformation

Ageing does not change blood granulocyte bactericidal capacity and levels of complement factors 3 and 4.

The bactericidal capacity of blood polymorphonuclear granulocytes and the plasma levels of complement factors 3 and 4 did not differ between 15 aged patients and 15 young control subjects, nor did these important antimicrobial functions predict morbidity and mortality in the next 6 months.