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Complement activating cryoglobulins in the nephritis of systemic lupus erythematosus.

Complement activation in vitro by cryoglobulins isolated from the sera of 28 patients with systemic lupus erythematosus (SLE) was examined by incubating the cryoglobulin with normal human serum and performing crossed-immunoelectrophoresis of the mixture to detect C3 conversion. Eighteen of the 28 SLE cryoglobulins activated complement; eight by the classical pathway, four by the alternative pathway exclusively, and six by both pathways. In contrast only two out of 20 cryoglobulins isolated from the sera of normal subjects activated complement and both did so by the classical pathway. Twenty-three of the 28 SLE sera activated complement and complement activating cryoglobulins were isolated from 15 of these 23 sera. The parent sera of cryoglobulins activating complement had lower C4 and C3 concentrations than sera whose cryoglobulins did not split complement but these differences were not significant. The ability of SLE cryoglobulins to activate complement in vitro suggests that these immune complexes activate complement in vivo and thus may contribute to tissue damage in this disease. The activation of both classical and alternative complement pathways is in keeping with other evidence that both pathways are involved in SLE.

Adult↗

Features of the two gene pairs RD-SKI2W and DOM3Z-RP1 located between complement component genes factor B and C4 at the MHC class III region.

Located at the 30 kb genomic region between complement factor B and component C4 are four ubiquitously expressed genes RD, SKI2W, DOM3Z and RP1. Besides RP1, the protein products of the other three genes each has highly conserved homologues or related proteins in lower eukaryotes, contains leucine zipper motifs for protein interaction, and plays important roles related to RNA metabolism. RD is a subunit of the negative transcription elongation factor, critical for the regulation of gene expression. It has an RNA recognition motif and 24 copies of Arg-Asp (RD) repeats. Ski2w is a nucleolar and cytoplasmic protein that has a putative RNA helicase domain. Fusion proteins of human Ski2w expressed in insect cells and bacteria have ATPase activity. The cytoplasmic protein of human Ski2w is associated with the polysomes and probably the 40S subunit of ribosomes. Ski2w is probably involved in the regulation of translation and RNA turnover. Dom3z is a nuclear protein whose yeast homologue forms a complex with an exoribonuclease. RP1 (or STK19) is a Ser/Thr nuclear protein kinase. No homologues of RP1 in lower eukaryotes have been discovered. Six polymorphic residues are present in human Ski2w and two in Dom3z. The potential roles of Ski2w and Dom3z on the clearance of degraded nuclear and cytoplasmic RNA raised their possibilities as susceptibility genes of systemic lupus erythematosus that is a disease with flawed processes in the removal of apoptotic materials.

Amino Acid Sequence↗

Complement components (C1, C2, C3, C4) in bronchial secretions after intranasal infection of guinea pigs with Mycoplasma pneumoniae: dissociation of unspecific and specific defense mechanisms.

Shortly after intranasal infection of guinea pigs with Mycoplasma pneumoniae, the titers of the complement components increased significantly in bronchial secretions by the folllowing amounts, compared with the titer of a control group: C1, about 2-fold; C2, 1.6-fold; C3, 17-fold; and C4, 942-fold. Histopathological signs of inflammation were not apparent at this time. At 2 weeks after infection, when the titers of complement components in the bronchial secretions were at the level of control values or lower, the serum antibody titer increased, and it reached the highest level at 6 weeks after infection. Therefore, one can distinguish two phases of reaction of the macroorganism to intranasal inoculation. The increase in complement components shortly after infection may represent an earlyunspecific defense mechanism of the host before the specific immune response becomes effective, since the complement system can be activated by M. pneumoniae via the classical as well as the alternative pathway in the absence of antibodies.

Administration, Intranasal↗

The significant of complement and immunoglobulin determination in healthy pregnant women and patients with EPH gestoses.

Complements C3 and C4, IgG, IgM, IgA and properdin factor B (PFB) were determined in maternal blood sera, sera from the umbilical cord and amniotic fluid in the group consisting of 30 healthy pregnant women and 30 patients with EPH gestoses. PFB and IgG were measured in urine, as well. Significant decrease of C3 complement in maternal sera and PFB in urine was found in the group with EPH gestoses, while a slight C4 complement enhancement was recorded in both maternal sera and the blood sera from the umbilical cord. PFB was conspicuously increased in maternal blood sera. IgG level was higher in the blood sera from the umbilical cord in comparison with that found in maternal sera in both groups examined. IgG, IgM and IgA levels were decreased in the group of patients with EPH gestoses in all fluids examined, while IgA level was significantly increased in the sera prepared from the blood from the umbilical cord.

Amniotic Fluid↗

[Fibrinolysis and complement-system profiles during aorto-femoral bypass implantation].

In 51 patients undergoing either implantation of an aortofemoral bypass (38 patients) or of an saphenous bypass (13 patients) the fibrinolytic and complement system profiles were determined. During the course of an aortofemoral bypass the plasminogen concentration decreased by 40%, alpha 2-macroglobulin by 25%, the complement factor C3c by 20% and the complement factor C4 by 40%. Antithrombin III concentration remained stable until the third postoperative day. The alpha 1-antitrypsin concentration increased postoperatively by 40% compared to the preoperative control. The concentrations of plasminogen, antithrombin III, alpha 2-macroglobulin and complement factor C4 did not change in the patients undergoing saphenous bypass operation. Intraoperatively the complement factor C3c decreased by 20%, while alpha 1-antitrypsin showed postoperatively an increase by 30%. Anaesthesia (neuroleptanaesthesia, halothane- or continuous thoracal epidural anaesthesia) had no influence on the fibrinolytic and complement system profiles. Neither could a correlation be shown between the intraoperative haemodynamic changes and the concentrations of the factors of the fibrinolytic and complement system.

Anesthesia, General↗

[Precipitable C4-poor immune complexes in HELLP syndrome and pre-eclampsia].

In 16 patients with HELLP syndrome and 10 patients with preeclampsia, laser nephelometric analysis of PEG-precipitated immunocomplexes revealed a decrease in the complement component C4. This is interpreted as a further indication of an immunologic component in the pathogenesis of these disorders.

Adolescent↗

Molecular genetics of the S region of the murine H-2 major histocompatibility complex.

The mouse H-2S region has been conventionally identified by the functional, serological and electrophoretic variations of two plasma proteins which constitute its primary genetic markers, C4 (the fourth component of complement) and C4-Slp (sex-limited protein). Recently, recombinant DNA procedures applied in our laboratory as well as in several others have made available molecular clones corresponding to these two nonallelic genes. This paper focuses on the progress provided by the study of C4 and C4-Slp cDNA and genomic clones, as well as by the application of such clones to the probing of the S region structure in conventional and special H-2 haplotypes. At variance with the K, I and D regions of H-2, the S region contains genes which have no obvious structural interrelationship, although in some cases they display a functional interaction. The heterogeneity of S region products is emphasized by the recent detection of steroid 21-hydroxylase genes associated with each of the C4 gene copies.

Alleles↗

The phylogeny and evolution of the thioester bond-containing proteins C3, C4 and alpha 2-macroglobulin.

The complement system is an effector of both the acquired and innate immune systems of the higher vertebrates. It has been traced back at least as far as the echinoderms and so predates the appearance of the antibodies, T-cell receptors and MHC molecules of adaptive immunity. Central to the function of complement is the reaction of the thioester bond located within the structure of complement components C3 and C4. The structural thioester first appeared in a protease inhibitor, alpha 2-macroglobulin, in which it is involved in the immobilisation and entrapment of proteases. An important development in the C3 molecule has been the acquisition of a catalytic His residue which greatly increases the rate of reaction of the thioester with hydroxyl groups and with water.

Amino Acid Sequence↗

A novel immunoassay for the quantitation of human C4 gene products.

Utilizing mouse monoclonal antibodies which recognize Rodgers 1 and Chido 1 epitopes carried on the C4A and C4B molecules, and heat-aggregated IgG to activate C1, an immunoassay was developed for the quantitation of total C4 as well as C4A and C4B. Interassay variation was 12.4, 11.5 and 10.8%, respectively. The immunoassay was compared to the quantitation of total C4 by radial immunodiffusion by testing 103 random white controls and gave a Pearson's product-moment correlation coefficient of 0.81. Three genetic total-C4-deficient individuals were nonreactive in all three assays. This activated assay is specific, reproducible, and superior to existing methods for the quantitation of C4A and C4B and detection of the heterozygous C4 null state.

Complement C4↗

Inheritance of serum autoantibody, reduced serum IgA and autoimmune disease in a canine breeding colony.

Immunological parameters were examined in 113 English cocker spaniel dogs from two breeding kennels. Dogs from kennel 1 (n = 86) were grouped as having idiopathic cardiomyopathy (n = 19), autoimmune or other disease (n = 7) or being clinically normal (n = 60). Dogs from kennel 2 (n = 27) were all clinically normal and used for comparative purposes. There was a high incidence of serum antinuclear antibody (ANA) amongst all groups from kennel 1 (39/82 dogs tested), with anti-thyroglobulin and anti-erythrocyte antibodies also recorded in a dog with systemic lupus erythematosus. Thirty percent of dogs with idiopathic cardiomyopathy had anti-mitochondrial antibody. Thirteen dogs from kennel 1 had reduced serum IgA (< or = 0.3 mg/ml), but there was no consistent abnormality in the concentration of serum IgG, IgM, complement C3 or C4 in these thirteen dogs, or other dogs from this kennel. No immunological abnormality was recorded in dogs from kennel 2. Pedigree analysis of dogs from kennel 1 revealed inheritance of autoimmune disease, serum ANA and low serum IgA within several breeding lines. Inheritance of idiopathic cardiomyopathy was recorded through three generations and a strong association demonstrated between the presence of this disorder and a particular complement C4 phenotype (C4: 4).

Animals↗

Serum immunoglobulin and complement levels in patients with sickle cell anaemia from eastern province of Saudi Arabia.

Serum immunoglobulin (IgG, IgA, IgM) and complement (C3, C4) levels were determined in 61 sickle cell anaemia patients of various age groups and both sexes in their steady state by nephelometry. Serum IgG was found to be consistently elevated in 46% cases of all age groups. Increase in the levels of IgA, IgM and in the complement values (C3, C4) was also observed. Although the mechanism responsible for these variations was unclear, however, this study gave an idea about the general pattern of serum immunoglobulin and complement levels in sickle cell anaemia patients from the Eastern Province of Saudi Arabia.

Adolescent↗

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