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Results for “Complement C4”

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PubMed1997

[Vascular intercellular adhesive molecule-1 (VCAM-1)--a new indicator of activity in systemic lupus erythematosus?].

The objective of the submitted study was to evaluate the role of the serum level of the soluble form of the vascular adhesive molecule-1(VCAM-1) in systemic lupus erythematosus (SLE) and to evaluate the possible relation to selected clinical and laboratory indicators of activity of the disease and cytokine serum levels. The analyzed group comprised 20 women, median age 37 years (range 18-65 years). Elevated VACM-1 serum levels were detected in 18 subjects (90%). Statistical analysis (Pearson's test, p < 0.05) revealed a significant relationship between serum levels of VCAM-1 and the index of clinical activity of SLE evaluated by the ECLAM system (European Consensus Lupus Activity Measurement), values of the C3 complement component, the level of antibodies against dsDNA and serum levels of IL-10. No significant correlation was found with levels of the soluble receptor IL-2 (sIL-2R) and the C4 complement component in serum. From the investigation ensues that investigation of serum levels of the adhesive molecule of the VCAM-1 type is a promising method which makes early diagnosis of exacerbation of the disease possible. However, for evaluation of its real asset in clinical practice a more widely conceived longitudinal investigation is needed.

Adolescent↗

PubMed1982

Complement components C3, C4, and Bf in six nonhuman primate species.

The extent of cross reactivity between antisera to human complement proteins [the third (C3) and fourth (C4) components and factor B (Bf)] and these proteins in the sera of six species of nonhuman primates was examined. Strong cross reactivity was found with these antisera and the specific complement proteins from rhesus monkeys, stumptailed macaques, cynomolgus macaques, patas monkeys, African green monkeys, and squirrel monkeys. Although molecular differences were apparent as indicated by differences in antigenic determinants and electrophoretic mobility, the antisera developed against human C3, C4, and Bf could be used to identify and to characterize these proteins in the nonhuman primate species examined.

Animals↗

PubMed1988

Autoimmunity and T-cell subpopulations in old age.

To investigate the interrelationship between T-cell-dependent immune functions and autoimmune phenomena in old age we determined T-cell subpopulations in 20 aged healthy individuals (80-96 years old) using monoclonal antibodies. These persons were also investigated as to humoral parameters such as antinuclear antibodies, rheumatoid factors (IgG-, IgA-, IgM-RF), antibodies to collagen types I-IV as well as autoantibodies to organ-specific antigens. In addition, immune complexes were determined. We found that aged individuals have an increased frequency of autoantibodies as compared to a young control population, each aged subject presenting with at least one autoantibody species. Immune complexes, however, were only rarely detected. Three individuals showed a slightly increased T-helper/T-suppressor cell ratio, four had a decreased ratio. An increased number of T-suppressor cells was significantly correlated with a lowered incidence of anticollagen antibodies. Other parameters tested by us: fibronectin, laminin, procollagen type III, C3 and C4 complement components, immunoglobulins and acid alpha 1-glycoprotein. Aged individuals have significantly higher serum levels of fibronectin, while laminin and procollagen concentrations are in the normal range. A large percentage of old individuals had increased serum levels of C3 and/or C4. The acute phase protein orosomucoid, however, was in the normal range.

Adult↗

PubMed1970

Genetically controlled total deficiency of the fourth component of complement in the guinea pig.

Guinea pigs with a total deficiency of the fourth component of complement (C4) have been discovered. There was no evidence for the presence of a C4 inhibitor in the serum of these animals. Mating studies indicate that C4 deficiency is transmitted as a simple autosomal recessive trait. A colony of these animals is being established at the National Institutes of Health. They will provide an opportunity to more precisely define the role of complement in immune phenomena and the defense against disease.

Animals↗

PubMed2003

Diversity in intrinsic strengths of the human complement system: serum C4 protein concentrations correlate with C4 gene size and polygenic variations, hemolytic activities, and body mass index.

Among the genes and proteins of the human immune system, complement component C4 is extraordinary in its frequent germline variation in the size and number of genes. Definitive genotypic and phenotypic analyses were performed on a central European population to determine the C4 polygenic and gene size variations and their relationships with serum C4A and C4B protein concentrations and hemolytic activities. In a study population of 128 healthy subjects, the number of C4 genes present in a diploid genome varied between two to five, and 77.4% of the C4 genes belonged to the long form that contains the endogenous retrovirus HERV-K(C4). Intriguingly, higher C4 serum protein levels and higher C4 hemolytic activities were often detected in subjects with short C4 genes than those with long genes only, suggesting a negative epistatic effect of HERV-K(C4) on the expression of C4 proteins. Also, the body mass index appeared to affect the C4 serum levels, particularly in the individuals with medium or high C4 gene dosages, a phenomenon that was dissimilar in several aspects from the established correlation between body mass index and serum C3. As expected, there were strong, positive correlations between total C4 gene dosage and serum C4 protein concentrations, and between serum C4 protein concentrations and C4 hemolytic activities. There were also good correlations between the number of long genes with serum levels of C4A, and the number of short genes with serum levels of C4B. Thus, the polygenic and gene size variations of C4A and C4B contribute to the quantitative traits of C4 with a wide range of serum protein levels and hemolytic activities, and consequently the power of the innate defense system.

Adult↗

PubMed1995

Cytokine-regulated production of the major histocompatibility complex class-III-encoded complement proteins factor B and C4 by human glomerular mesangial cells.

Local production of complement within normal or diseased kidneys could be of importance during local inflammatory reactions. In the present study, we demonstrate that human MCs are able to synthesize the MHC class-III-encoded complement proteins factor B and C4 in vitro. This synthesis is strongly upregulated following stimulation with cytokine-containing supernatants of activated peripheral blood mononuclear cells. All primary cell lines tested so far are able to synthesize factor B and C4 after stimulation. To determine more specifically whether defined cytokines are able to enhance factor B and C4 complement production, MCs were stimulated with IL-1 alpha, IFN-gamma, and TNF-alpha. Factor B synthesis was increased in a dose-dependent fashion by IL-1 alpha, TNF-alpha, and IFN-gamma, whereas C4 synthesis was only upregulated by IFN-gamma. Furthermore, factor B synthesis was upregulated after stimulation with IFN-alpha, -beta, and -gamma and C4 synthesis only by IFN-gamma. The synthesis of factor B and C4 was inhibited by cycloheximide, suggesting de novo protein synthesis. The cytoplasmic localization of both components was shown by immunofluorescence studies. Northern and dot blot analysis revealed induction of factor B and C4 mRNA after stimulation with cytokines.

Cells, Cultured↗

PubMed1991

Diminished IgG, but not complement C3 or C4 or factor B, precedes nosocomial bacterial sepsis in very low birth weight neonates.

The significance of low serum IgG and complement proteins in very low birth weight (VLBW; less than 1500 g) neonates is not known. Therefore serum IgG, C3, C4 and Factor B were quantitated weekly by rate nephelometry in 15 VLBW neonates who developed proven nosocomial bacterial or candidal sepsis (Group A) and 27 VLBW neonates who did not develop sepsis (Group B). In the first week of life the serum IgG of neonates in Group A was 295 +/- 33 mg/dl (mean +/- SEM) and in Group B it was 440 +/- 21 mg/dl (P less than 0.01). In the second week, the IgG of Group A was 270 +/- 32 mg/dl and that of Group B was 473 +/- 38 mg/dl (P less than 0.01). If the IgG was less than 350 mg/dl in the first week or less than 230 mg/dl in the second week, the relative risk of acquiring sepsis was greater than or equal to 5 (95% confidence interval in the first week, 1.7 to 11.2). The serum IgG was measured before the onset of sepsis in 14 of the 15 neonates in Group A. In the week before sepsis the IgG of the 14 neonates was less than 440 mg/dl (range, 45 to 433 mg/dl) in all cases, was below the mean IgG of Group B in 12 of 14 cases (P = 0.006 vs. Group B) and was greater than 2 SD below the mean IgG of Group B in 4 of 14 cases (P = 0.0003 vs. Group B).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

PubMed1994

Hemolytically inactive C4B complement allotype caused by a proline to leucine mutation in the C5-binding site.

The fourth component of complement (C4) is encoded by two highly homologous genes, C4A and C4B. Only one hemolytically inactive C4A allotype (C4A6) has been reported. No hemolytically inactive C4B allotype has been described. We report the first hemolytically inactive (hi) allotype of C4B, C4B*1 (hi). This unique variant was first recognized by hemolytic overlay assays and confirmed to segregate in the affected pedigree with the major histocompatibility complex haplotype A28,B35,CW4,DR6, C4A3,C4B1(hi), BFF,C2C. By single strand conformational polymorphism, we detected only a migration variant in exon 12 caused by a C to T transition in the second base of codon 459. This mutation results in a leucine substitution for proline (P459L) 1 residue downstream of a residue known to contribute to the C5-binding site. Allele-specific oligonucleotide analysis of samples demonstrated cosegregation of the mutation with the hemolytically inactive allotype in the affected pedigree. Site-directed mutagenesis and expression studies showed that the P459L mutation causes loss of hemolytic function. C4B*1(hi) is the first example of a circulating C4B protein lacking detectable hemolytic activity and the P459L mutation expands our knowledge of the C5-binding site of C4.

Base Sequence↗

PubMedDate not supplied

[Changes of IgA, IgG and IgM immunoglobulins and of 10 other plasma proteins in patients with duodenal ulcer treated with ranitidine].

In 25 patients with duodenal ulcer, before treatment and after three weeks, and another 30 days of treatment with ranitidine, plasma concentrations were determined of IgA, IgG, IgM immunoglobulins, and of 10 other proteins. In comparison to the control group of 20 persons, a statistically significant decrease was found in the concentration of alpha 2-M, prealbumins, and IgG, as well as a significant increase of alpha 1-AT, C4 complement component, and a non-significant increase of coeruloplasmin, haptoglobin and IgM. During the treatment a tendency was observed for an increase of IgG and IgM level, as well as a statistically significant decrease of alpha 1-AT, C4, and coeruloplasmin concentration. The treatment exerted no effect on the decreased level of alpha 2-M. It was accepted that the tendency for an increase of IgG and IgM level was due, most probably, to the immunostimulating action of ranitidine, and the changes of concentrations of other parameters induced by the treatment were related to the presence and healing of the ulceration. The observed decrease of alpha 2-M level was probably due to binding of alpha 2-M to pepsinogen whose blood level was increased during gastric ulcer.

Adult↗

PubMed1977

The significance of serial measurement of serum anti-native DNA antibodies and complement C3 and C4 components in the management of patients with systemic lupus erythematosus.

Serial measurements were made over a period of three years of serum DNA-binding capacity and complement C3 and C4 levels in parallel with documentation of clinical features of disease activity in Glasgow patients with SLE. Raised DNA-binding levels were noted in 27 of the 32 patients over this time period. High levels (over 80%) were found in patients with both renal and non-renal disease. In some patients increases in DNA-binding capacity and decreases in C3 levels were associated with changes in disease activity. This pattern was commonest in patients with renal SLE. In others DNA-binding capacity was elevated without any relationship to SLE disease activity. A fall in serum C3 levels was usually significant while serum C4 levels frequently fell without any change in clinical features of disease activity. Very low serum C4 levels (below 15 mg/dl), however, were usually of clinical relevance. The uses of immunological measurements in the differential diagnosis of a major illness in a patient with SLE are discussed. The finding of such an illness in a patient with normal serum DNA-binding levels made it unlikely that the illness was due to an exacerbation of the SLE and more likely that an alternative cause such as supervening bacteraemia was responsible.

Antibodies↗

PubMed1991

Selective IgA deficiency, IgG subclass deficiency, and the major histocompatibility complex.

Here we have examined the connection between IgA deficiency, IgG subclass deficiency, and the absence of alleles of complement C4, and show that IgA deficient subjects who have IgG subclass deficiencies may also have an increased frequency of C4 null alleles. In our group, we found an increased incidence of HLA B38 which might reflect the ethnic composition of the patients tested. While family studies are of primary importance to assess the relationships between histocompatibility antigens and immune deficiency, these studies are complicated by the observation that C4 null alleles are not always inherited with the humoral defect.

Adult↗

PubMed2004

Regulation of complement C3 and C4 synthesis in human peritoneal mesothelial cells by peritoneal dialysis fluid.

Although complement is activated in the peritoneal cavity during chronic peritoneal dialysis (PD), little is known about its role in peritoneal defence and injury related to long-term PD. We examined the impact of glucose and commercial peritoneal dialysis solutions on complement expression in HPMCs obtained by primary culture from omental tissues of consented patients undergoing elective abdominal surgery. Constitutive expression of C3 and C4 mRNA in HPMCs was up-regulated upon exposure to 75 mm glucose in a time-dependent manner. C3 and C4 protein was secreted in both apical and basolateral directions. Glucose doses beyond 100 mm markedly down-regulated C3 and C4 expression, and stimulated LDH release dose-dependently. Such cytotoxic effects were attenuated using equivalent doses of mannitol instead of glucose. Treatment with conventional lactate-buffered dialysis solution gave rise to down-regulation of C3 and C4 expression, and heightened LDH release in HPMCs. These effects correlated with the glucose strength of the solution, persisted despite replacement with a bicarbonate-buffered solution, aggravated by glycated albumin, and were partially abrogated by supplementation with 10% fetal bovine serum in the culture system. Our findings suggest that the artificial conditions imposed by PD lead to alterations in local complement synthesis that have implications for the role of the peritoneal mesothelium in both inflammation and defence.

Cell Membrane Permeability↗

PubMed1989

Stimulation of histamine receptors of human monocytoid and hepatoma-derived cell lines and mouse hepatocytes modulates the production of the complement components C3, C4, factor B, and C2.

The influence of histamine (and the related agonists and antagonists) alone or in the presence of recombinant human interleukin 1 alpha (IL-1 alpha) and gamma interferon (IFN-gamma) was studied on the production of complement components C3, C2, factor B, and C4 in vitro with human monocytoid cell line U937, hepatoma-derived cell line HepG2, and mouse hepatocytes. Both U937 and HepG2 cells responded to histamine through H1 and H2 histamine receptors. The effect of histamine on the biosynthesis and gene expression of complement proteins was predominantly enhancing via the H1 histamine receptors and inhibitory through the H2 receptors. The actual predominance of the histamine receptor involved (and the outcome of the ligand interaction) seemed to be greatly affected by the simultaneous activation of the cells by IL-1 or IFN-gamma.

Animals↗

PubMed1985

Normal macrophage function in infants receiving Intralipid by low-dose intermittent administration.

The effect of soybean oil emulsion (Intralipid) therapy on serum complement levels was determined in infants who received Intralipid therapeutically (1 gm/kg over 12 hours, every other day). The effect of Intralipid on macrophage priming for increased superoxide anion production was studied in a mouse model. Intralipid administration did not affect either macrophage function. Serum levels of C2 and C4, complement components synthesized and secreted exclusively in macrophages, were not decreased either during the week the infants received Intralipid or in the week following administration. Macrophages from mice that had received Intralipid produced similar amounts of superoxide anion, as did macrophages from mice that had received saline solution. Our data suggest that macrophages in infants receiving Intralipid in this regimen will function normally.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1999

An unequal crossover between the RCCX modules of the human MHC leading to the presence of a CYP21B gene and a tenascin TNXB/TNXA-RP2 recombinant between C4A and C4B genes in a patient with juvenile rheumatoid arthritis.

The RCCX module of the human MHC class III region is comprised of four genes arranged in tandem: RP, complement C4, steroid 21-hydroxylase (CYP21), and tenascin X (TNX). Variations in the number and genes of the RCCX modules may lead to genetic and/or autoimmune diseases. Restriction fragment length polymorphism (RFLP) analysis was utilized to determine the RCCX modular variation in patients with juvenile rheumatoid arthritis (JRA). In JRA patient L1, RFLP analysis suggested the presence of a bimodular RCCX structure containing both C4A long and C4B short genes, yet missing the markers for the CYP21A and TNXA genes usually located between the C4A and C4B genes. The 7.5-kb genomic fragment spanning the CYP21-TNX-RP2 genes was cloned and sequenced, revealing that a genetic recombination occurred between TNXA of a bimodular RCCX chromosome and TNXB of a monomodular RCCX chromosome. This recombination results in a new MHC haplotype with a CYP21B gene and a TNXB/TNXA-RP2 recombinant between the two C4 genes. Elucidation of the breakpoint region provides further evidence for the instability of the MHC class III gene region as a result of the RCCX modular variation.

Amino Acid Sequence↗

PubMed2002

Pneumonia-associated acute glomerulonephritis.

OBJECTIVE: Post-infectious glomerulonephritis typically occurs 7-14days after an infection. However, in several children we observed acute glomerulonephritis (AGN) to develop concurrently with pneumonia. The objective of the study was to delineate the clinical course and outcome of pneumonia-associated AGN. STUDY DESIGN: The hospital database was searched from 1984 - 1999 for c+hildren admitted with both acute pneumonia and AGN, each diagnosis having been made within 72 hours of each other. RESULTS: 11 boys, age 3.8- 12.7 years, were identified. Ten children had lobar pneumonia and I had an interstitial infiltrate. All responded to antibiotic therapy with resolution of fever and respiratory symptoms. Only I child developed an empyema. The mean +/- SD hospital stay was 5.9 +/- 3.9 days. All patients had an abnormal urinalysis with hematuria (gross hematuria in 5), proteinuria and cellular casts. At presentation, 7 children had a serum creatinine > 1.0 mg/dl and creatinine clearance < or = 80 ml/min/1.73 m2; in all, serum creatinine returned to normal and the creatinine clearance was > 80 ml! min/1.73 m2 on follow-up. Nine of the 11 children had a low serum complement C3, 3 of whom also had low complement C4. Anti-streptolysin-O (ASO) titers were elevated in all 10 children tested. Six children developed hypertension and received antihypertensive medications. Only I child was severely oliguric requiring peritoneal dialysis for 4 days. He underwent a kidney biopsy, which showed acute proliferative glomerulonephritis without crescents. Neither a biopsy nor dialysis was performed in the other children. At follow-up, blood pressure, urinalysis and serum complements had normalized in the 9 children in whom follow-up was available. CONCLUSION: Children with pneumonia who are found to have abnormal urinalysis. hypertension, azotemia or oliguria should be evaluated for concomitant glomerulonephritis. In most children, pneumonia-associated AGN runs a benign course and has a good prognosis, however, in some short-term medical intervention may be necessary.

Acute Disease↗

PubMed2004

Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury.

Reperfusion injury of ischemic tissue represents an acute inflammatory response that can cause significant morbidity and mortality. The mechanism of injury is not fully elucidated, but recent studies indicate an important role for natural antibody and the classical pathway of complement. To test the hypothesis that injury is initiated by specific IgM, we have screened a panel of IgM-producing hybridomas prepared from peritoneal cells enriched in B-1 cells. One clone, CM22, was identified that could restore pathogenic injury in RAG-1(-/-) mice in an intestinal model of ischemia/reperfusion (I/R). In situ activation of the classical pathway of complement was evident by deposition of IgM, complement C4, and C3 in damaged tissue after passive transfer of CM22 IgM. Sequence analysis of CM22 Ig heavy and light chains showed germ-line configurations with high homology to a V(H) sequence from the B-1 repertoire and a V(K) of a known polyreactive natural IgM. These data provide definitive evidence that I/R injury can be initiated by clonally specific natural IgM that activates the classical pathway of complement. This finding opens an avenue for identification of I/R-specific self-antigen(s) and early prevention of injury.

Animals↗

PubMed2000

Effects of lead on immune parameters in occupationally exposed workers.

BACKGROUND: To assess the immune competence of workers occupationally exposed to lead, several subsets of peripheral lymphocytes, i.e., T, TCD4(+), TCD8(+), B, NK cells, serum immunoglobulin and complement protein concentrations, chemotaxis, and intracellular killing activity of neutrophils of 25 male storage battery workers have been analyzed and compared to 25 healthy males with no history of lead exposure. RESULTS: The results of this study which indicated that industrial exposure to lead resulting in group mean blood lead concentrations of 75 +/- 18 microg/dl are associated with a significant depression of: T helper lymphocytes, Ig G, Ig M and C3, C4 complement levels, chemotaxis, and random migration of neutrophils. No correlation was found between the duration of exposure and the altered immune parameters. CONCLUSIONS: The immune system can be a target for lead toxicity and elimination of lead hazard in working places is necessary.

Adult↗