C4B gene polymorphism detected in a human cosmid clone.
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Chromosome Mapping↗
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Results for “Complement C4”
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Quantitation of human C4A and C4B, in serum and plasma by enzyme-linked immunoadsorbent assay.
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Alleles↗
Complement system activation by contrast media in neuroradiology.
Complement system activation was studied in six series of 12 patients undergoing routine contrast study following IV injection of five recently developed contrast media. The decreasing order of effectiveness on the complement system was as follows: ioxaglic acid, metrizamide, iodamidol. Metrizoic and ioxithalamic acids did not provoke any complement depletion at the doses used in this study. Both pathways of activating the complement system were involved. We could not find any definite correlation with osmolarity, ionic or nonionic formulation, protein binding, or hydrophobicity.
Complement Activation↗
Analysis of the proinflammatory property of epidermal cyst contents: chemotactic C5a anaphylatoxin generation.
We investigated in vitro the contents of epidermal cysts for complement activation and found that they activated complement mainly through the alternative pathway. Chemotactic C5a anaphylatoxin produced by the cyst contents after contact with serum most likely plays a significant role in the initiation and aggravation of inflammation in ruptured epidermal cysts. Our additional study disclosed that components of three representative follicular resident microorganisms (Pityrosporum ovale, Propionibacterium acnes, and Staphylococcus epidermidis) also produced C5a anaphylatoxin mainly through the alternative pathway; the C5a production was more vigorous than that by a virulent pathogen, Staphylococcus aureus. These results suggest that accidental colonization of the cyst contents by these follicular microbial flora further augments the inflammatory changes in ruptured epidermal cysts.
Adult↗
Susceptibility to IDDM is marked by MHC supratypes rather than individual alleles.
107 patients with insulin-dependent diabetes mellitus (IDDM) were typed for HLA A, B, C-, and DR antigens, and for complement C4A, C4B, and Bf alleles, and the results were compared with those of a combined reference group of 332 appropriately matched healthy subjects. Supratypes (allelic combinations) were identified from the phenotype of each group, and it was shown that the frequency of several supratypes is increased in patients with IDDM, in particular supratypes (A1 Cw7) B8 C4AQ0 C4B1 BfS DR3 (P = 0.0001), (A30 Cw-) B18 C4A3 C4BQ0 BfF1 DR3 (P = 0.0003), (A2 Cw3) B62 C4AR C4B2.9 BfS DR4 (P = 0.0002), and three other supratypes including DR4. It was also shown that increases in the frequency of individual alleles are secondary to increases in supratype frequency. Moreover, supratypes appeared to interact; the presence of two relevant supratypes being particularly important. The absolute risk of IDDM was approximately 0.5 in subjects who were homozygous for B18 C4A3 C4BQ0 BfF1 DR3. We concluded that genetic susceptibility is best recognized by MHC supratypes rather than isolated alleles, and that supratype combinations make the identification of even greater disease risk possible.
Alleles↗
DNA antibodies and complement in SLE patients. A follow-up study.
Sixty-seven patients with systemic lupus erythematosus (SLE) were followed up for 3-19 months (mean 12) in a prospective study. The activity of SLE was estimated on clinical grounds and correlated with DNA antibody and complement levels. The disease reactivations consisted mostly of articular and cutaneous symptoms. There were 17 relapses and 22 complicating infections during the follow-up period. The levels of antibodies to native, double-stranded (ds) DNA (P less than 0.001) and antibodies to denatured, single-stranded (ss) DNA of IgG class (P less than 0.001) and C3 (P less than 0.001) correlated best with disease activity, which was estimated on the clinical symptoms and signs. These assays were not reliable, however, in predicting minor exacerbations. The levels of IgM class ss-DNA antibodies were significantly higher in SLE patients without nephritis than in SLE nephritis patients. In most cases, the combination of IgG class ss-DNA antibody and complement (C3 and CH50) determinations differentiated SLE relapse from infection.
Autoantibodies↗
[Methodological and clinical studies on the properdin system. III. Studies on the behavior of 4 complement components after major gynecological operations].
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Biomedical Research↗
HLA complement gene polymorphisms in multiple sclerosis. A study on 80 Italian patients.
We studied C4A, C4B, and Bf complement gene polymorphisms in 80 Italian patients with multiple sclerosis (MS). We observed a significantly higher frequency of C4AQ0 allele in patients with the relapsing-remitting form of MS than in ethnically homogeneous controls. Restriction fragment length polymorphism analysis by Southern blotting of the C4/CYP21 gene complex showed that a structural gene deletion was present in 45% of patients with the C4AQ0 allele. Our data support the hypothesis that relapsing-remitting MS and primarily chronic progressive MS are immunogenetically distinct diseases; further, complement factor abnormalities typical of autoimmune diseases could influence the pathogenesis of MS.
Case-Control Studies↗
Comparative study on biological activities of various anaphylatoxins (C4a, C3a, C5a). Investigations on their ability to induce platelet secretion.
Several anaphylatoxic substances (human C3a, guinea pig C3a, human C4a, guinea pig C5a, and a synthetic C3a-related hexapeptide) were compared with regard to their ability to induce secretion of [3H] serotonin from guinea pig platelets. Functional identity of the C3a preparations, C4a, and the hexapeptide was demonstrated by the phenomenon of crossed desensitization. Whereas C3a of human and guinea pig origin proved to be qualitatively and quantitatively identical, C4a expressed only 3% of the activity of the C3 fragments on a molar basis. Investigations with goat anti-guinea pig C3a demonstrate that human and guinea pig C3a possess one antigenic determinant in common; however, this determinant is not the C-terminal amino acid sequence. Addition of the anaphylatoxins with low doses of thrombin led to a potentiation of [3H] serotonin release from the platelets. Under these conditions C3a concentrations of 1.5 X 10(-10) mumol/liter (65 pg of C3a) could be detected. Thus the platelet system represents the most sensitive in vitro assay known for evaluation of biological activity of the C3a anaphylatoxins.
Anaphylatoxins↗
Parasitological and immunological aspects of Trypanosoma cruzi infection in nude rats.
The role of the thymus on immunity of rats against Trypanosoma cruzi infection was investigated in vivo. The athymic (nu/nu) rats were shown to be significantly more susceptible to the acute phase of the infection than the control nu/+ rats, as measured by increased parasitemia and mortality. Specific anti-T. cruzi antibodies, complement, IgM and IgG2a serum levels were determined. The results would indicate the essential role of antibodies in immunity to acute Chagas' disease through T-dependent immune response.
Animals↗
Acquired c1-inhibitor deficiencies in lymphoproliferative diseases with serum immunoglobulin abnormalities. A study of three cases.
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Aged↗
Structural and functional studies on C4b-binding protein, a regulatory component of the human complement system.
The binding and cofactor activities of C4b-binding protein were examined before and after limited proteolysis by pepsin, trypsin and chymotrypsin. The major fragments generated were characterized by amino acid sequencing, thus establishing the precise points of limited proteolysis. These studies allow a tentative assignment of the cofactor activity site to the residues 177-322 of the 549 amino acid long chain of C4b-binding protein but indicated that residues in the region 332-395 are important in the binding activity.
Amino Acid Sequence↗
Effect of dehydroepiandrosterone on hereditary angioedema.
Hereditary angioneurotic edema (HAE) is a complement-related clinical disorder with a deficiency of the C1 esterase inhibitor protein. Eight patients with severe attacks of the disease were treated with the adrenal "androgen" dehydroepiandrosterone sulphate (DS). Steroid therapy for 3-28 months resulted in dramatic improvement in their clinical state and a moderate increase in the serum concentration of C1 inhibitor. There was a significant increase in the serum level of either unconjugated dehydroepiandrosterone (D) or of DS during treatment.
Adolescent↗
Mapping of prolactin and tumor necrosis factor-beta genes on human chromosome 6p using lymphoblastoid cell deletion mutants.
A collection of human B lymphoblastoid cell lines (LCLs) was used to map two genetic sequences for which polymorphism had not been identified: human prolactin (PRL) and tumor necrosis factor-beta (TNFB). The LCLs have overlapping deletions on chromosome 6p produced by gamma-irradiation of LCL 721. After using two chromosome 6p sequences for which LCL 721 is heterozygous to validate our scanning densitometry (SD) method for inferring gene copy number, SD was used to map TNFB and PRL. TNFB maps to the interval between the C4 complement and HLA-B loci within the MHC on chromosome 6p. PRL lies within the 6p21.3-6p22.2 interval distal to HLA-C. We found that LCL 721 is heterozygous for PRL DNA fragment lengths generated by HpaII but not MspI digestion, indicating that the two copies of PRL in LCL 721 are differentially methylated. This novel methylation RFLP was used to corroborate the region PRL assignment.
Blotting, Southern↗
[Lymphocyte function in children with iron deficiency].
In 23 children with mild iron-deficiency anemia, 22 children with latent iron-deficiency, and in 46 healthy controls the 3H-thymidine incorporation in blood lymphocytes after stimulation with phytohemagglutinin, concanavalin A, pokeweed mitogen, and serum against thymocyte cells was measured. In 11 of the children with iron-deficiency anemia, in 13 of the children with latent iron-deficiency, and in 20 controls the lymphotoxin secretion after phytohemagglutinin stimulation was also performed. All patients studied were without intercurrent infections and were well nourished. No alteration of the lymphocyte function in the patients was found. The concentrations of immunoglobulins and the components C3 and C4 of complement system were also found to be normal. It is suggested that lymphocyte functions are eventually only altered in more severe states of iron-deficiency anemia.
Anemia, Hypochromic↗
The early diagnosis of impending coagulopathies following surgery and multiple trauma.
Blood coagulation problems, either disseminated intravascular coagulation (DIC) or adult respiratory distress syndrome (ARDS) are frequent complications during the recovery of the polytraumatized surgical patient or accident victims. The key to their successful control lies in prompt recognition and aggressive treatment of the disease as soon as it appears. Unfortunately their onset is not usually well defined clinically and success in handling usually depends upon clinical expertise in recognising "high risk" situations coupled with measurements in the haematological laboratory of changes in plasma coagulation factors. It is suggested in this communication that a relatively simple examination of plasma complement profiles in the high risk, intensive care patient, may not only provide early warning of the onset of a coagulopathy but also distinguish the type. Simple tests are described, based on the assessment of plasma complement C5 levels, which have a high predictive value for the onset of ARDS, a disease with few early clinical manifestations and notably lacking in early changes in haematological parameters. In prospective trials complement tests correctly identified 18 patients who later developed ARDS but were no more effective than haematological tests in the identification of 24 patients who subsequently developed DIC.
Blood Protein Electrophoresis↗
Immune complex p24 antigen: a new prognostic marker in human immunodeficiency virus infection.
p24 antigen (p24 Ag) is usually not found in patients in the asymptomatic phase of HIV infection, mainly because it is bound to anti-p24 antibodies (p24 Ab), with which it forms immune complexes. Nine asymptomatic patients positive for HIV-1 antibodies (stage II CDC criteria) treated with r alpha-interferon were followed (7.5 +/- 0.5 months), and a basal and final sample were tested for p24 Ag immune complexes (p24 Ag-IC), free p24 Ag, p24 Ab, CD4 count, beta 2-microglobulin, properdin B factor, and C3 and C4 complement fractions. p24 Ag-IC was detected in 55.5% of the samples, whereas free p24 Ag was detected in 5.5%. The finding of no change or an increase in p24 Ag-IC serum levels may be considered a prognostic marker. We believe that p24 Ab cannot be used as a prognostic marker unless p24 Ag-IC detection is simultaneously evaluated.
Antigen-Antibody Complex↗
Complement studies in children with treated coeliac disease after gluten challenge.
Changes of the complement components in the sera of 13 children with treated coeliac disease were studied after gluten challenge. The levels of C 1 and C3-activator (factor B) were significantly decreased at 4 h after the challenge, as were the levels of total complement (CH 50) and the components C 1, C 4 and C 1-inactivator at 8 h. After 24 h most values returned to normal but there was another significant decrease in serum C 4 after 24 h, and for CH 50, C 1, C 2 and C 4 after 48 h.
Celiac Disease↗