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PubMed1981

Amino acid sequence around the proposed thiolester bond of human complement component C4 and comparison with the corresponding sequences from C3 and alpha 2-macroglobulin.

The amino acid sequence around the proposed thiolester bond in human complement component C4 has been determined. The sulphydryl and reactive acyl groups involved in the intrachain thiolester bond are contained in a short section of sequence which shows almost complete identity with the equivalent sequence from alpha 2-macroglobulin and C3. Other regions of homology between the three proteins near the proposed thiolester bond are also apparent.

Amino Acid Sequence↗
PubMed1999

Modular variations of the human major histocompatibility complex class III genes for serine/threonine kinase RP, complement component C4, steroid 21-hydroxylase CYP21, and tenascin TNX (the RCCX module). A mechanism for gene deletions and disease associations.

The frequent variations of human complement component C4 gene size and gene numbers, plus the extensive polymorphism of the proteins, render C4 an excellent marker for major histocompatibility complex disease associations. As shown by definitive RFLPs, the tandemly arranged genes RP, C4, CYP21, and TNX are duplicated together as a discrete genetic unit termed the RCCX module. Duplications of the RCCX modules occurred by the addition of genomic fragments containing a long (L) or a short (S) C4 gene, a CYP21A or a CYP21B gene, and the gene fragments TNXA and RP2. Four major RCCX structures with bimodular L-L, bimodular L-S, monomodular L, and monomodular S are present in the Caucasian population. These modules are readily detectable by TaqI RFLPs. The RCCX modular variations appear to be a root cause for the acquisition of deleterious mutations from pseudogenes or gene segments in the RCCX to their corresponding functional genes. In a patient with congenital adrenal hyperplasia, we discovered a TNXB-TNXA recombinant with the deletion of RP2-C4B-CYP21B. Elucidation of the DNA sequence for the recombination breakpoint region and sequence analyses yielded definitive proof for an unequal crossover between TNXA from a bimodular chromosome and TNXB from a monomodular chromosome.

Adrenal Hyperplasia, Congenital↗
PubMedDate not supplied

[Evaluation of complement component C4 concentration and immunoglobulins IgA, IgG, and IgM in serum of patients with primary essential hypertension].

The aim of the study was to determine serum concentration of complement component C4 and IgA, IgG, IgM immunoglobulins in hypertensive patients and healthy controls as well as to assess the interrelationships regarding some immunological and clinical data in the study group. The study group consisted of 81 hypertensive patients (with secondary forms of hypertension excluded), 44 females and 37 males (mean age 51.2 +/- 14.5 years). The control group comprised 34 healthy volunteers, 19 females and 15 males (mean age 47.5 +/- 15.3 years). C4, IgA, IgG, IgM serum concentrations were evaluated with turbidymetry. C4 serum concentration was significantly higher in hypertensive patients when compared to the controls. No significant differences in IgA, IgG, IgM serum concentrations existed between the groups. The duration of hypertension correlated positively with C4 serum concentration. Elevated C4 serum concentration may be one of the markers of immunological disturbances existing in hypertensive patients. IgA, IgG, IgM immunoglobulins do not seem to be directly associated with essential hypertension.

Adult↗
PubMedDate not supplied

Immunological parameters in patients with epilepsy.

Various immunological parameters (IgA, IgG, IgM serum levels, C3 and C4 complement components and T and B lymphocytes and T-lymphocyte subsets) were determined in 50 patients with epilepsy (20 without medication, 15 on carbamazepine and 15 on valproate) and in 20 controls. The epileptic group had fewer CD4 and more CD8 lymphocytes, while the CD4/CD8 ratio was lower; the levels of IgG and IgM were increased and C4 complement component was also decreased. Patients without medication showed all the above mentioned abnormalities. Patients on carbamazepine had a lower CD4/CD8 ratio, increased IgG and IgM levels and decreased C4 complement component while patients on valproate had more CD8 lymphocytes, a lower CD4/CD8 ratio, increased levels of IgM and decreased C4 complement component. Our results indicate that there is a defective immune mechanism in epileptic patients modified by treatment.

Adolescent↗
PubMed1984

Immune complexes and the complement factors C4 and C3 in cerebrospinal fluid and serum from patients with chronic progressive multiple sclerosis.

Immune complexes (IC) have been found in both serum and cerebrospinal fluid (CSF) in multiple sclerosis (MS). The complement system is known to play a major role as a mediator of inflammation in immune complex disease. Therefore, we have investigated paired samples of serum and CSF from 32 patients with progressive MS for IC, the levels of the complement factors C4 and C3, and presence of their activation products (AP). IC was found in serum from 17 of the 32 MS patients (53%) and in CSF from 9 of 31 MS patients (29%). No correlation was found between the occurrence of IC in serum and in CSF. The levels of C3 in serum and CSF from the MS patients did not differ from the levels in a control group, whereas the levels of C4 in MS-serum were elevated and the C4 levels in MS-CSF reduced. A low level of CSF-C4 correlated significantly to the occurrence of CSF-IC. AP of C4 and C3 in serum were seen in 11 of the 32 patients (34%), appearing significantly more frequently among patients with circulating IC. No C4- or C3AP could be identified in CSF.

Adult↗
PubMed1993

Complement (C3, C4) and C-reactive protein responses to cardiopulmonary bypass and protamine administration.

Complement activation has been deemed responsible for the damaging effects of cardiopulmonary bypass (CPB) in patients undergoing open heart surgery. We studied C3, C4 and C-reactive protein (CRP) in 22 patients undergoing CPB. In Group 1 (11 patients), protamine was given intravenously and in Group 2 (11 patients), via the aortic root after CPB. Significant decreases were observed in C3 and C4 during CPB in both groups indicating complement activation primarily by the classic pathway. Protamine did not lead to further activation of the complement system. In both groups, C3 levels gradually returned toward baseline within 24 hours but C4 levels were still lower than baseline 24 hours postoperatively. CPB and protamine administration did not cause any significant changes in CRP levels, but CRP increased abruptly 24 hours after operation. Although activation of complement system during CPB is expected to invoke an acute phase response, we conclude that this period is not long enough to induce an increased production of CRP in response to tissue injury or inflammation.

Adult↗
PubMedDate not supplied

[Seroimmunological profile of kala-azar in Tunisia].

165 sera of patients suffering from kala-azar were collected before and after treatment (N-methyl glucamine: Glucantime ) and analysed for anti-leishmania antibodies by the counter immunoelectrophoresis and fluorescent antibody techniques. Serum immunoglobulins G, A, M and Complement C4 and C3 were studied as well; and C reactive protein, rheumatoid factor and anti-nuclear, anti-mitochondrial and anti-smooth muscle antibodies were investigated. Before treatment, counter immuno-electrophoresis was positive in 63.88% and immunofluorescent antibody test in 94.6%. The analysis of immunoglobulins has shown an increase of IgG in nearly all cases, an increase of IgM in 78.26% of sera tested. Little change has been noted with IgA. C reactive protein has been found in 87.67% and rheumatoid factor in 76.4% of sera examined. In 4 patients, anti-smooth muscle antibodies have been found at a relatively weak dilution. A decrease of complement C4 has been observed whereas complement C3 was slightly increased. After treatment (2 cures of Glucantime ) counter immunoelectrophoresis was positive in 23.07% of cases whereas immunofluorescent antibody test was still positive in 84.62%. IgG remained increases in the whole cases and IgM in only 43,48%. C reactive protein and rheumatoid factor have been found in 14.81% and 50% of cases respectively. Complement C4 remained low whereas complement C3 showed normal mean value. The relationship between the serological disturbances observed and the prognosis were discussed.

Antibodies↗
PubMedDate not supplied

[Levels of total hemolytic complement, C3, C4 and antibodies against the myocardium in rheumatic fever].

The levels of the hemolytic complement (UH 50%), C3, C4 and the antibodies against myocardium and against the antigenic fractions of myocardium precipitated with ammonium sulphate were studied in 8 patients with active rehumatic fever (ARF), 28 with inactive rheumatic fever (IRF) and 26 people without cardiopaties (NI). The UH 50% was low in 2 out of 36 patients with rheumatic fever (RF). C3 was normal and C4 low in 12.5% of the ARF patients. C3 had subnormal values in 25% and C4 in 33% of IRF patients, this last value had a stadistic significant decrease with respect to the values of C4 in normal people. The 36 patients with RF had antibodies against the myocardium and also against the heart antigenic fractions precipitated with 10% ammonium sulphate. 11.5% of the normal group had anti-myocardial antibodies and none had antibodies against the fractions. The levels of anti-streptolysin-O and C-reactive protein were higher in the ARF group than in the patients with IRF or the normal people. The participation of the hemolytic complement, the anti-myocardium antibodies, the anti-streptococcus antibodies and the cytophilic activity in the etiopathogeny of rheumatic fever is discussed.

Autoantibodies↗
PubMed1982

[Intranuclear alpha 1-antitrypsin in HBs-Ag-seronegative hepatitis B with PAS-negative globular hyaline bodies containing the complements components C4, C3, and C3-activator (author's transl)].

In the liver biopsy specimen of a 16 year old patient with HBsAg-seronegative hepatitis B PAS-negative globular hyaline bodies reacted with antibodies to the complement components C4, C3, and C3-activator, but not with antibodies to alpha 1-antitrypsin. However, alpha 1-antitrypsin could be identified in the liver cell nuclei, cytoplasm, and cell membrane. Probably, these findings are caused by an hereditary or acquired metabolic disorder.

Adolescent↗
PubMed2004

Characterization of the interaction between human complement protein C4 and a single-chain variable fragment antibody by capillary electrophoresis and surface plasmon resonance.

Immunoaffinity capillary electrophoresis and surface plasmon resonance have been used for the characterization of the interaction between two large-sized proteins, the human complement protein C4 and the single-chain variable fragment C43. The rather high kinetic rate constants as determined by surface plasmon resonance pointed out that a capillary electrophoresis method had to be applied, in which the labeled C4 is preincubated with C43 before injection and the same concentration of C43 is included in the running buffer. Analysis of the concentration dependence of the small mobility shift of the fluorescent C4 signal upon binding of C43 resulted in a dissociation constant that was comparable to the one obtained with surface plasmon resonance. This study is one of the few examples where capillary electrophoresis is successfully used to characterize the interaction between large proteins.

Antibodies↗
PubMed2000

C1q-binding peptides share sequence similarity with C4 and induce complement activation.

Two peptide motifs that bind to C1q have been identified from phage displayed libraries. A first panning cycle recovered phage that displayed a [N/S]PFxL motif. A synthetic peptide with that motif blocked those phage from binding to C1q. A second panning cycle was conducted with the [N/S]PFxL motif peptide present, leading to recovery of phage displaying a different motif, SHY. The two motifs are specific for C1q and are competed by DNA and the cognate synthetic peptide but not by immunoglobulins. Phage displayed peptide sequences containing the [N/S]PFxL have significant sequence similarity to a region of complement component C4, suggesting a possible site of interaction between C4, or one of its processed forms, and C1q. The SHY motif peptide induces C4 consumption in a hemolytic assay, suggesting that it activates C1 independent of immune complexes. This peptide may activate C1 by a mechanism similar to the beta-amyloid peptides found in Alzheimer's disease.

Animals↗
PubMed1984

Drugs that induce systemic lupus erythematosus inhibit complement component C4.

The syndrome resembling systemic lupus erythematosus (SLE) associated with long-term treatment with hydralazine and isoniazid seems to be due to the drugs themselves rather than their metabolites. This syndrome is associated with deposition of immune complexes; and in the complement system inhibition of C4 is likely to increase deposition of immune complexes. In vitro, hydralazine and isoniazid inhibited 50% of the binding of C4 at 840 mumol/l and 1.05 mmol/l, respectively--ie, within the concentration ranges that have been used in therapy. Acetylated metabolites were not inhibitory at the maximum concentrations tested; and iproniazid, which does not cause SLE, gave 50% inhibition only at a concentration far exceeding that used in therapy.

Acetylation↗
PubMed1985

Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man.

The genes for four components (C) of complement in the human major histocompatibility complex (HLA) have been aligned previously in a series of overlapping cosmid cloned inserts. Those inserts, which contained the two C4 genes C4A and C4B, hybridized with human adrenal mRNA, indicating that they contain a gene expressed in the adrenal. The mRNA fraction of 2.4 kilobases (kb) hybridizes with genomic DNA of 4.5 kb, which is duplicated and lies about 1.5 kb 3' of both the C4A and the C4B complement genes. Sequencing of a 430-base section and comparison with the published cDNA sequence of bovine cytochrome P-450 21-hydroxylase, peptide sequences of porcine 21-hydroxylase, and a cDNA sequence of a rat liver cytochrome P-450 identified the gene as coding for human steroid 21-hydroxylase [steroid,hydrogen-donor:oxygen oxidoreductase (21-hydroxylating), EC 1.14.99.10]. Mapping of the gene was helped by use of a synthetic oligonucleotide based on the bovine cDNA sequence.

Adrenal Glands↗