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PubMed1988

Molecular heterogeneity of complement component C4-null and 21-hydroxylase genes in systemic lupus erythematosus.

C4A-null alleles (C4A*Q0) and hereditary complete C4 deficiency (homozygous C4A*Q0,C4B*Q0) are associated with systemic lupus erythematosus (SLE). Using Southern blot analysis with C4 and 21-hydroxylase (21-OH) DNA probes, we studied SLE patients and normal control subjects with or without C4A*Q0, and 2 C4-deficient SLE patients. A previously reported large C4A,21-OHA gene deletion associated in normal subjects with the HLA-A1;B8;DR3;C4AQ0 haplotype was detected by the appearance of a new C4 Hind III 8.5-kb fragment and disappearance of a 3.2-kb 21-OH Taq I fragment. In 3 SLE patients with homozygous C4A*Q0 and 15 with heterozygous C4A*Q0, this deletion pattern occurred almost exclusively in association with the HLA-B8;DR3;C4A*Q0 phenotype; the one exception was a black SLE patient. Other C4A*Q0-bearing HLA phenotypes in white patients and black patients with SLE, and the 2 completely C4-deficient SLE patients, had normal DNA hybridization to both C4 and 21-OH probes. The genetic basis for C4-null alleles in SLE is heterogeneous. A large C4A,21-OHA deletion occurs mainly on the HLA-B8;DR3;C4AQ0 haplotype in SLE and controls. Other HLA haplotypes bearing C4A*Q0 have normal C4 and 21-OH genes, as demonstrated by Southern blot analysis.

Alleles↗
PubMed1979

Isolation of the fourth component (C4) of rat complement.

The fourth component of rat complement was purified to homogeneity by sequential chromatography of rat plasma in benzamidine on QAE-A50, SP-C50, hydroxyapatite, and gel filtration on Bio-Gel A 1.5. The final material was homogeneous on SDS-PAGE analysis and had a calculated m.w. of 198,000. A monospecific antibody against rat C4 was obtained from immunized rabbits. The concentration of rat C4 in the plasma of normal 4-month-old Wistar rats was 190 +/- 34 microgram/ml (mean +/- 1 S.D.).

Animals↗
PubMed1986

Relationship between secretory IgA, IgA-containing (C3-fixing) circulating immune complexes, and complement components (C3, C4) in patients with obstructive jaundice.

Serum secretory IgA, IgA-containing circulating immune complexes (IgA-CIC), complement components, and major immunoglobulins were measured in patients with biliary tract stones and/or tumors of the biliary tract or pancreas. The levels of secretory IgA and total IgA were increased in patients with and without obstructive jaundice. The levels of both C3 and C4 were significantly higher in patients with or without obstructive jaundice than in healthy controls. In patients with obstructive jaundice the increased levels of secretory IgA, total IgA, and IgA-CIC were correlated with the increase of C3 but not with that of C4.

Adult↗
PubMed1984

Humoral immune system and ulcerative colitis activity. II. Complement level.

C4, C3 and C5 levels and the complement hemolytic activity were analysed in 84 ulcerative colitis patients and correlated with activity, extension and duration of the disease, with the presence of extraintestinal manifestation, and with therapeutic effects. The elevation of C3 was observed in both mild active and in severe colitis. Only C3 correlated with disease activity and with C-reactive protein level. On the other hand, C4 and C5 levels were significantly decreased in the active disease extended to the left side or to total great bowel. The importance of these findings is discussed. No significant connection of the examined complement components with duration, therapy and extraintestinal manifestation was observed. A trend to increase the complement hemolytic activity in severe colitis was noted. Our study of complement and its components activity suggests the secondary role of analysed parameters in pathogenesis of UC and clinical usefulness of C3 level as an indicator of the disease activity.

Adolescent↗
PubMed1975

Complement components of C3 and C4 in Nigerians.

Serum complement component of C3 was lower in both Nigerian children and adults in corresponding British subjects whereas the concentrations of C4 were similar in all groups. It would appear that in the ontogeny of the complement system the concentration of C4 reaches adult level before that of C3.

Adult↗
PubMed1979

Serum complement (C3 and C4) levels in the Malaysian adult population.

Serum C3 and C4 values were determined in 236 normal adults of three racial groups, using the single radial immunodiffusion techniques. The C3 levels varied from 47 to 119 mg/dl and C4 levels from 16 to 66 ml/dl (mean +/- 2SD). The values were found to be comparable to the normals reported in some Western series. No significant differences in the levels related to sex and race were found.

Adolescent↗
PubMed1979

The significance of serial measurements of serum complement C3 and C4 components and DNA binding capacity in patients with lupus nephritis.

Eighteen patients with systemic lupus erythematosus (SLE) and proliferative glomerulonephritis, underwent serial serum determinations of C3, C4, and native DNA binding capacity, as well as repeat renal biopsy 7 to 48 months (median 25 months) following initial biopsy. Highly significant correlations were found between serum C3 levels and renal histologic changes (P less than 0.0001), and between serum C3 levels and DNA binding capacity (P less than 0.03). Histologic deterioration correlated with depressed C3 levels, while improvement was associated with normalization of C3 levels. No correlation between renal histologic changes and either serum C4 levels or DNA binding capacity was found. The data suggest that the serum level of C3 is the best index of activity of lupus nephritis.

Adolescent↗
PubMed2004

Circulating immune complexes and complement C3 and C4 levels in a selected group of patients with rhinitis in Lebanon.

BACKGROUND: A number of reports indicate that circulating immune complexes (CIC) and activation of the complement system contribute to the pathogenesis of Type I allergy. The aim of this study was to investigate the status of CIC in 113 patients with rhinitis in Lebanon and determine complement components C3 and C4 serum levels in the CIC-positive patients. Serum specific IgE antibodies were previously detected and reported in 74 of the 113 patients. METHODS: CIC were detected by polyethylene glycol precipitation and serum C3 and C4 levels quantified by radial immunodiffusion. RESULTS: CIC was positive in 20 of the specific IgE-positive and 13 of the specific IgE-negative patients. C3 and C4 levels were within the normal range in all the 33 CIC-positive patients. CONCLUSIONS: The antibody class that constitutes the complexes does not seem to be IgG or IgM. Moreover, complement activation does not seem to be involved in the allergic reaction since both C3 and C4 levels were normal in all patients. The role of these complexes, if any, in the pathogenesis of rhinitis is yet to be determined.

Journal Article↗
PubMed2000

Cellular localization of complement C3 and C4 transcripts in intestinal specimens from patients with Crohn's disease.

It has been suggested that the increase in C3 and C4 levels in jejunal perfusates of patients with Crohn's disease (CD) results from local intestinal synthesis of complement. The present study evaluated the expression of these complement genes in inflamed tissues from patients with CD. Surgically resected specimens from patients with CD and control tissue obtained from subjects with adenocarcinoma of the colon were evaluated for C3 and C4 gene expression by the use of 35S-labelled anti-sense RNA probes. All tissue samples, diseased and normal tissue, expressed C4 mRNA throughout in the intestinal epithelium. C3 mRNA was not detected in epithelial cells in histologically normal tissue, but in diseased specimens there was a focal distribution of C3 mRNA in epithelial cells of the crypts, but not in villous epithelium. Focal C3 gene expression correlated with crypt abscess formation and the presence of polymorphonuclear leucocytes in the lumen of the crypts. In addition, C3 mRNA was also found in macrophages of the submucosa. These macrophages were CD68+, fusiform with faint cytoplasm and morphologically different from the large rounded lamina propria macrophages, which do not express C3 mRNA. Multinucleated giant cells did not express either C3 or C4 genes. In addition to its presence in intestinal epithelium, C4 mRNA was also expressed in mast cells, which however did not express C3 mRNA. These observations identify cells in the intestinal wall expressing complement genes and support the hypothesis that there is local regulated production of complement in the intestine of patients with CD, and subsequent complement activation may contribute to the inflammatory process.

Adrenal Cortex Hormones↗
PubMed1988

Secretor state and complement levels (C3 and C4) in insulin dependent diabetes mellitus.

Lower levels of C3 and C4 components of the complement system have been reported for patients with insulin dependent diabetes mellitus (IDDM) but not among those with non-insulin dependent diabetes (NIDDM). We have found a significantly higher proportion of patients who are non-secretors of the ABO blood group antigens among patients with IDDM but not among those with NIDDM. As the gene that controls secretion of these antigens is in the same linkage group as that for the C3 complement component, we compared the levels of C3 and C4 of patients with IDDM by secretor state. The mean level of C3c for 45 non-secretors (75.2 IU/ml) was significantly lower than that found for 59 secretors (86.4 IU/ml) (p less than 0.025). The level of C4 among non-secretors (77.1 IU/ml) was also significantly lower than that of secretors (96.3 IU/ml) (p less than 0.025). The significance of these observations is discussed.

ABO Blood-Group System↗
PubMedDate not supplied

[Presence of cryoprecipitates in the serum of patients with rheumatoid arthritis].

Serum samples from 140 controls (C) and from 72 patients suffering from defined rheumatoid polyarthritis (RP) were tested for cryoglobulins (CG). CG were found in 19.7 percent of C and 55 percent of RP : a highly significant difference (p less than or equal to 0.001). In the controls there was no correlation between the CG and age or sex. The RP with cryoglobulins seemed to have more inflammation, but systemic manifestations were not any more frequent than in the cryonegative RP. In the RP a correlation was noted between the presence of CG and the following parameters : increase in the sedimentation rate, rise in serum immunoglobulins, IgA and IgC, presence of antinuclear factors, and drop in the C4 fraction of complement. There was no correlation with the presence of the rheumatoid factor in the serum. In 33 cryoprecipitates in the RP, 7 contained IgG, 1 IgM, 22 IgM-IgG -- of which 11 contained C1q and 16 rheumatoid factor -- and 3 contained IgA-IgM-IgG -- of which 1 contained C1q and 2 rheumatoid factor. Some of the biochemical data support the hypothesis that likens these cryoglobulins to immune complexes.

Adult↗
PubMed1977

A solid phase fluorescent immunossay for the quantitation of the C4 component of human complement.

A non-competitive method for the determination of the C4 component of human complement in serum is described. This procedure involves use of a specific antibody covalently attached to derivatized polyacrylamide beads and a fluorescently labeled specific antibody. Reproducible results were achieved for C4 in serum in the range of 10 mg/dl to 170 mg/dl within 2 h. C4 levels as low as 150 ng/ml can also be measured. Fluorescent immunoassay and radial immunodiffusion were used to determine C4 levels in healthy adults. Good agreement was found between the two methods.

Complement C4↗
PubMed1996

Influence of hepatic mitochondrial redox state on complement biosynthesis and activation during and after cardiopulmonary bypass operations.

We have proposed the hazardous phenomena associated with cardiopulmonary bypass (CPB) are due to metabolic derangement by hepatic mitochondrial dysfunction during and after CPB. On the contrary, complement activation and consumption during CPB is reported to be related to the morbidity associated with cardiac surgery. To determine the significance of the hepatic mitochondrial function on the morbidity of cardiac surgery, we measured the serum levels of complements (C3 and C4), activated complements (C3a and C4a), and the arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state, in 30 patients undergoing CPB. The AKBR, which was at a normal level preoperatively, dropped to a critical level after the initiation of CPB and remained at a low level during the CPB, returning to the preoperative level on the second postoperative morning in a time dependent fashion. The patients group were assigned to two groups according to their AKBR on the first postoperative morning. Group I consisted of patients whose AKBR had recovered to above 0.7 on the first postoperative morning (n = 16). Group II consisted of the rest of the patients (n = 14). The serum complement concentration had considerably decreased by the end of bypass, but recovered in a time-dependent fashion after CPB. The group I patients (C3: 71% of its preoperative value, C4: 85% of its preoperative value) recovered their complements more quickly than the group II patients (C3: 56% of its preoperative value, C4: 54% of its preoperative value). However, the serum C3a and C4a concentrations increased by the end of bypass (C3a: 806% of its preoperative value, C4a: 341% of its preoperative value). The activated complements were significantly higher in the group II patients (C3a: 124% of its preoperative value, C4a: 236% of its preoperative value) than in the group I patients (C3a: 75% of its preoperative value, C4a: 113% of its preoperative value) on the first postoperative morning. It is suggested that hepatic mitochondrial function is related to recovering the complements and to reducing the activated complements after CPB.

Adolescent↗
PubMedDate not supplied

Isolation and initial characterisation of complement components C3 and C4 of the nurse shark and the channel catfish.

Complement components C3 and C4 have been isolated from the serum of the nurse shark (Ginglymostoma cirratum) and of the channel catfish (Ictalurus punctatus). As in the higher vertebrates, the fish C4 proteins have three-chain structures while the C3 proteins have two-chain structures. All four proteins have intra-chain thioesters located within their highest molecular mass polypeptides. N-terminal sequence analysis of the polypeptides has confirmed the identity of the proteins. In all cases except the catfish C3 alpha-chain, which appears to have a blocked N-terminus, sequence similarities are apparent in comparisons with the chains of C3 and C4 from higher vertebrates. We have confirmed that the activity/protein previously designated C2n is the nurse shark analogue of mammalian C4. This is the first report of structural evidence for C4 in both the bony and cartilaginous fish.

Amino Acid Sequence↗
PubMed1977

[Heterogeneity of antinuclear antibodies (ANA), immunoglobulin- and complement levels in sera of patients with rheumatoid arthritis (RA) (author's transl)].

ANA typing of RA patients according to the heavy- and light chains, complement fixing ability and immunofluorescent staining pattern was performed by the immunofluorescence technique and partially by qualitative immunoelectrophoresis. In the corresponding sera the immunoglobulins and complement components were quantiatively determined. Dependent on the ANA-immunoglobulin classes we found the following distribution: IgG-ANA; 40/93 (43%), IgM-ANA: 19/93 (20%), IgA-ANA: 2/93 (2%), and Ig-comb.-ANA:17/93 (18%). ANA only positive for polyspecific antimmunoglobulin serum: 15/93 (16%). After L-chain typing we found within a given ANA-Ig-class positivity for both L-chain subclasses (kappa and lambda): IgG-ANA: 19/40 (48%), IgM-ANA: 3/19 (16%), IgA-ANA:1/1 and Ig-comb.-ANA: 14/17 (82%). ANA cases within a given Ig-class only positive for the L-chain/type kappa:IgM-ANA:6/19 (32%), IgG-ANA: 9/40 (23%), Ig-comb.-ANA:2/12 (12%). ANA cases within a given Ig-class only positive for the L-chain type lambda: IgM-ANA: 7/19 (37%), IgG-ANA: 3/40 (8%), Ig-comb.-ANA:1/17 (6%) and IgA-ANA:1/1. In all cases of restricted ANA-positivity (only positive by use of polyspecific anti-immunoglobulin serum) no light chains were detected. In total we found approximatively 25% of complement fixing ANA, predominantly IgG-ANA (70%). Concerning the immunofluorescent nuclear staining we stated the following patterns: homogenous: 34/93 (36.6%), speckled: 29/93 (31.2%), mixed pattern : 22/93 (23.6%) peripheral: 5/93 (5.4%) and nucleolar: 3/93 (3.2%). The quantitative Ig-determination reveals a significant increase of IgG in ANA (single type) positive sera. IgG + IGM + IGA-ANA and IgG + IgM-ANA are found together with a significantly increased IgG- and IgM-serum levels, in the case of IgG + IgM-ANA we could demonstrate an additional relative decrease of the complement component C4. Sera with positive complement fixing ANA compared with non complement fixing ANA are characterized by an absolute increase of IgG and relative decrease of the complement component C4. No differences in serum-immunoglobulin- and -complement concentrations were registered dependent on ANA-immunofluorescent staining patterns.

Antibodies, Antinuclear↗