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PubMed2002

[Long-term analysis of clinical disease activity and chronic organ damage in patients with systemic lupus erythematosus].

BACKGROUND: Systemic lupus erythematosus is a chronic inflammatory and systemic disease with multiple symptoms which is often characterized by a course of exacerbations. Over the last few decades the prognosis of SLE considerably improved with >90% patients living more than 10 years with their disease. AIM OF THE STUDY AND METHODS: The aim of this retrospective-descriptive analysis of 65 patients with the diagnosis of SLE (based on the ARA criteria) was to investigate the symptoms and the laboratory values at the time of diagnosis (TD) and over a period of 10 years (10Y) in the outpatient university clinic of the Department of Nephrology and Rheumatology at Goettingen. In addition to symptoms and laboratory values, disease activity, exacerbations, chronic organ failure, and medical therapy were to be investigated. RESULTS: The long-term analysis revealed a decline in the prevalence of ANAs (TD: 95.6%; >10Y: 78.6%), ds-DNA antibodies (TD: 78.0%; >10Y: 46.7%) and pathological levels of the complement component C3 (TD: 72.7%; >10Y: 42.9%) over time. The symptoms most prevalent at the time of first diagnosis such as the typical butterfly rash (TD: 50.0,%; >10Y: 36.8%), discoid skin lesions (TD: 38.8%; >10Y: 23.5%) were noted less often after a 10 year-disease course. On the contrary the frequency of arthralgias (TD: 61.2%; >10Y: 57.9%), myalgias (TD: 26.1%; >10Y: 26.3%) and fatigue (TD: 63.0%; >10Y: 64.7%) remained stable over time. The prevalence of arterial hypertension (TD: 17.2%; >10Y: 54.5%), proteinuria (TD: 33.3%; >10Y: 66.7%) and erythrocyturia (TD: 27.8%; >10Y: 44.4%) remarkably increased during the disease course. Besides renal damage, coronary artery disease (TD: 6.0%; >10Y: 23.0%) and neurological disease (e.g., cerebrovascular insults) (TD: 10.9%; >10Y: 26.3%) were noted more often after 10 years. Of patients, 56.9% developed one or several exacerbations of the disease. In all cases, clinical symptoms correlated with an increase in the level of ds-DNA-antibodies and a decrease of C3-complement component. Other medications included immunosuppressants, antihypertensive drugs and NSAIDs. High-dose steroids were preferred as the first diagnosis (TD: 44.4%; >10Y: 11.1%), while low-dose steroids were more often prescribed after a 10-years diseases course (TD: 6.7%; >10Y: 27.8%). CONCLUSIONS: There is a shift towards secondary organ damage with a decline of the inflammatory activity in patients with SLE after 10 years of disease. These consecutive diseases are due to the primary damage of SLE as well as to medical treatment (e.g., with steroids).

Adolescent↗
PubMed1977

Severe steroid-responsive nephrosis associated with hypersensitivity.

Sensitivity to cow's whole milk investigated in six patients with the idiopathic nephrotic and an elemental diet was given. After proteinuria had decreased to less than or equal to 500 mg/24 hours on consecutive days patients were challenged with cow's milk. This resulted in the return of significant proteinuria, oedema, and decreased urine volume together with a decrease in serum-IgG concentrations in four patients. Acute alteration of plasma C3 complement component accompanied milk challenge in all 6 patients. There were no consistent alterations in other immunoglobulin concentrations. Intradermal skin testing with cow's milk extract was positive in all patients. These results suggest that in some individuals clinical and biochemical manifestations of the nephrotic syndrome of childhood may be related to hypersensitivity of food products.

Adolescent↗
PubMedDate not supplied

Modification of mediators of immune reaction after general anaesthesia.

UNLABELLED: The adverse reactions that may occur during a surgical intervention are of concern to anesthesiologists and allergists due to the civil responsibility they entail and the increased demand for healthcare in allergology units. The aim of the present study was to determine the prevalence of adverse reactions in our setting (Island of Lanzarote) and modifications to immune response mediators using three types of representative myorelaxants (succinylcholine, cisatracurium and vecuronium) in order to predict and prevent adverse reactions. MATERIAL AND METHODS: We performed a prospective, cross sectional, observational study in a population of 201 patients scheduled to undergo surgery in the Surgery Department of the Lanzarote General Hospital from October 1998. Three groups were retrospectively selected: vecuronium (73 patients), cisatracurium (80 patients), and succinylcholine (48 patients). Blood was extracted from all patients before and after the intervention and the following in vitro variables were evaluated: histaminemia, eosinophil cationic protein, tryptase, IgE to latex, CD4/CD8 fractions, total lymphocytes, total IgE, C3 and C4, and also the histaminuria. CONCLUSIONS: The mean age of the patients was 41 years with a predominance of women. Sixty percent had not previously undergone surgery. The mean operating time was 2 hours. Digestive surgery accounted for the greatest number of interventions (38.8 %) and most of the patients had no personal history of atopy (91.5 %). The greatest number of perioperative reactions was produced by cisatracurium (38.8 %), followed by succinylcholine (27.4 %) and vecuronium (20 %). The reactions observed were immediate type 1 and 2 reactions. All reactions were reversible without sequelae. Histaminuria levels were significantly decreased in the cisatracurium group. Histaminemia and eosinophil cationic protein showed no significant changes in any of the three groups. Tryptase concentrations in blood did not increase in the postoperative period in any of the three groups. On the contrary, concentrations were significantly lower than basal values. In the vecuronium and succinylcholine groups, CD4/CD8 fractions decreased in the postoperative period. Total lymphocytes decreased in all three groups. Total IgE tended to decrease in the cisatracurium and succinylcholine groups. IgE to latex was negative in the three groups. Specific IgE to succinylcholine was unmodified. C3 complement fraction was unmodified in all three groups and C4 fraction was reduced in the vecuronium group. In our setting and in our patients, the three myorelaxants produced immunosuppression of immune response mediators. The present study confirms that tests for allergy to myorelaxants are not indicated in the preoperative period.

Adolescent↗
PubMed1990

Investigation on the humoral immune response in patients with gastro-intestinal cancer.

The humoral immune reactivity was studied in patients affected by gastro-intestinal cancer. The number of peripheral B lymphocytes, the concentration of serum immunoglobulins (Ig) and of C3 complement factor and the frequency of circulating immuno complexes (CIC) did not significantly differ between patients and age-matched controls, while the C4 factor level was significantly increased. The frequency of serum monoclonal components (M-components) was higher in the patients than in the elderly subjects. Moreover the results concerning the "in vitro" functional response of patient B lymphocytes showed a significant decrease of the proliferative responses to Staphylococcus Aureus Cowan I (SAC) and a significant increase of the IgG and IgM synthesis by peripheral blood mononuclear cells (PBMC) in unstimulated and pokeweed mitogen (PWM) stimulated cultures. The meaning of these results, taken together with those reported by others, is discussed.

Adult↗
PubMed1984

Binding capacity of sera from systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) to C3c. Evaluation by enzyme linked immunosorbent assay (ELISA).

Immunoconglutinins (IKs) are autoantibodies directed against antigenic determinants on C3 complement component. An ELISA was performed to detect IKs in sera from 50 RA patients, 50 SLE patients and 50 normal subjects. Comparison showed significantly higher levels in patients than in normal subjects (p less than 0.001) and higher IKs levels in RA than in SLE (p less than 0.001). IKs were not related to others biological tests, except a statistically significant inverse correlation between IKs and circulating immune complexes levels detected by conglutinin binding assay in RA.

Adult↗
PubMed1993

[Effect of mistletoe lectin therapy on serum level of defined serum proteins (acute phase proteins) in tumor patients].

The influence of galactoside-specific mistletoe lectin (ML-1) administration on defined acute phase reactants in the serum of cancer patients (mammary carcinoma, n = 4; larynx carcinoma, n = 11; TNM-stages II to IV; after appropriate surgery, chemotherapy, radiation) was studied. Regular subcutaneous injections of the optimal doses of ML-1 (1 mg/kg body weight, twice a week) yielded statistically significant increases of certain acute phase reactants (C-reactive protein, haptoglobin, coeruloplasmin, C3-complement, albumin, immunoglobulin IgM) after four weeks of treatment. However, serum concentrations of transferrin, C4-complement and the immunoglobulins IgG and IgA were found within the biological range (means +/- 2 s). The increase of acute phase reactants after administration of ML-1 correlates positively with the activity of lymphatic cells (e.g. expression of IL-2 and HLA-DR receptors) in FACS (fluorescence-activated cell sorter) staining experiments and indicates the immunoreactive potency of this substance which may be speculated to be cytokine-induced.

Acute-Phase Proteins↗
PubMed2004

[Determination of serum acute phase reaction protein in patients with severe acute respiratory syndrome].

OBJECTIVE: To study the diagnostic value of determinations of serum acute phase reaction protein, such as complement 3 (C3), complement 4 (C4), prealbumin (PA) and C-reactive protein (CRP), etc., in patients with severe acute respiratory syndrome (SARS). METHODS: Serum levels of C3, C4, PA and CRP were determined by turbidimetry in 54 cases of SARS, 20 of other pneumonia and 30 normal persons. RESULTS: Serum concentrations of C3, C4, CRP and PA were (1.18 +/- 0.42) g/L, (1.15 +/- 0.56) g/L, (10.52 +/- 8.77) mg/L and (107 +/- 54) mg/L in SARS patients, (1.30 +/- 0.46) g/L, (0.57 +/- 0.31) g/L, (0.88 +/- 0.43) mg/L and (291 +/- 76) mg/L in patients with other pneumonia, and (1.11 +/- 0.56) g/L, (0.38 +/- 0.26) g/L, (0.42 +/- 0.26) mg/L and (376 +/- 74) mg/L in normal persons, respectively. Serum level of PA was significantly lower and levels of C4 and CRP significantly in patients with SARS higher than those in patients with other pneumonia and normal persons (P < 0.01). There was no significant difference in serum level of C3 between the three groups (P > 0.05). CONCLUSION: Determination of serum level of C4, CRP and PA in suspected patients is beneficial to early differential diagnosis for SARS.

Acute-Phase Proteins↗
PubMed1985

Isolation of human complement factors C3, C5 and H.

An improved method for simultaneous purification of complement factors C3, C5 and H from human plasma has been developed. Using an initial batch separation technique with QAE-Sephadex, followed by chromatography on SP-Sephadex and gel filtration in Sephadex G-200, 600 mg of highly pure C3 can be prepared from 1600 ml of plasma. Simultaneously about 70 mg of highly pure factor H and 30 mg of C5 are obtained by chromatography of post SP-Sephadex material on DEAE-Sephacel. A small amount of C3 in the C5 pool is removed by anti-C3-Sepharose. By maleylation or citraconylation of reduced and alkylated C3, the constitutive polypeptide chains are modified in a way that made them separable by ion exchange chromatography.

Chromatography, Gel↗
PubMed1992

Mutagenesis of the Arg-Gly-Asp triplet in human complement component C3 does not abolish binding of iC3b to the leukocyte integrin complement receptor type III (CR3, CD11b/CD18).

The leukocyte integrin complement receptor type III (CR3, CD11b/CD18) binds the C3 cleavage product iC3b. Many other integrins bind their ligands via an Arg-Gly-Asp (RGD) triplet. Both the RGD-containing C3 peptide 1390TRYRGDQDATMS1401 (pro-C3 numbering) and the RGD-like fibrinogen peptide GGAKQAGDV, which binds to the platelet integrin glycoprotein IIb-IIIa, were shown to inhibit the iC3b-CR3 interaction, suggesting that this binding is also RGD-mediated (Wright, S.D., Weitz, J.I., Huang, A. J., Levin, S.M., Silverstein, S.C., and Loike, J.D. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7734-7738). However, unlike other integrin-ligand interactions, that of CR3 and iC3b is unaffected by the hexapeptide GRGDSP, and substitutions in the RGD triplet of C3 from other species appear to be tolerated. It was, therefore, proposed (Grossberger, D., Marcuz, A., du Pasquier, L., and Lambris, J.D. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 1323-1327) that the highly conserved DATMS portion of the inhibitory C3 peptide may have been responsible for its binding. To address these inconsistencies and directly assess the role of the 1390-1401 segment within the complete iC3b molecule in mediating binding to CR3, a human C3 cDNA was altered by site-directed mutagenesis and the expressed recombinant proteins were examined in a CR3-specific assay. Replacement of RGD by AAA did not abolish rosetting of the corresponding iC3b-coated erythrocytes to human CR3-bearing leukocytes. In addition, mutant iC3b molecules in which the positively charged R1391 (corresponding to K in the fibrinogen peptide) and the highly conserved 1397DATMS sequence were replaced by Q and NAAMA respectively, were still bound by CR3. We conclude that the iC3b-CR3 interaction is not mediated by the RGD triplet or its neighboring residues.

Amino Acid Sequence↗
PubMed1986

Serotherapy of primary rat mammary carcinoma: inhibition by ethylenedinitrilotetraacetic acid but not by [ethylenebis(oxyethylenenitrilo)]tetraacetic acid.

We reported inhibition of growth of primary rat mammary carcinomas after infusions of tumor-bearer plasma absorbed with Protein A-Sepharose or inactivated CNBr Sepharose. Absorbed plasmas were depleted of the third component of complement (C3) (other complement components defined similarly) and C5 but not C1, C4, or C2. These results suggested that activation of the alternative pathway of complement might be involved in the observed antitumor effects. To test this concept sera were treated with ethylenedinitrilotetraacetic acid or [ethylenebis(oxyethylenenitrilo)]tetraacetic acid before absorption with Protein A-Sepharose. Ethylenedinitrilotetraacetic acid, by chelating calcium and magnesium, prevents activation of both the alternative and classical complement pathways. [Ethylenebis(oxyethylenenitrilo)]tetraacetic acid, by chelating calcium but not magnesium, permits activation of the alternative pathway but inhibits activation of the classical complement pathway. Sera in the presence or absence of chelating agent were absorbed with Protein A-Sepharose twice at room temperature. After absorption calcium was added to the sera. Rats were treated by i.v. injection of sera twice a week for 2 weeks. Measurements of tumor size were made weekly for 5-7 weeks and then tumor weight was determined. Groups were compared both for size of index and total tumors. The results can be summarized as follows: tumor-bearer sera before absorption did not inhibit the growth of rat primary mammary carcinomas; tumor-bearer sera after absorption with Protein A-Sepharose showed significant consumption of C3 and did inhibit tumor growth; tumor-bearer sera absorbed in the presence of ethylenedinitrilotetraacetic acid did not show a decrease in C3 functional activity and did not inhibit tumor growth; tumor-bearer sera absorbed in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid did show a decrease in C3 functional activity and did inhibit tumor growth; sera from normal adult female rats after absorption with Protein A-Sepharose did inhibit tumor growth. The results are consistent with a role for the alternative pathway of complement in the inhibition of growth of rat primary mammary carcinomas observed after treatment with absorbed sera.

Animals↗
PubMed1999

Identification of residues within the 727-767 segment of human complement component C3 important for its interaction with factor H and with complement receptor 1 (CR1, CD35).

Mapping approaches employing blocking antibodies and synthetic peptides have implicated the 727-767 segment at the NH2 terminus of C3b alpha'-chain as contributing to the interactions with factor B, factor H, and CR1. Our previous mutagenesis study on the NH2-terminal acidic cluster of this segment identified residues Glu-736 and Glu-737 as contributing to the binding of C3b to factor B and CR1 but not factor H. We have now extended the charged residue mutagenic scan to cover the remainder of the segment (738-767) and have assessed the ability of the C3b-like C3(H2O) form of the mutant molecules to interact with factor H, CR1, and membrane cofactor protein (MCP) using a cofactor-dependent factor I cleavage assay as a surrogate binding assay. We have found that the negatively charged side chains of Glu-744 and Glu-747 are important for the interaction between C3(H2O) and factor H, a result in general agreement with an earlier synthetic peptide study (Fishelson, Z. (1991) Mol. Immunol. 28, 545-552) which implicated residues within the 744-754 segment in H binding. The interactions of the mutants with soluble CR1 (sCR1) revealed two classes of residues. The first are residues required for sCR1 to be an I cofactor for the first two cleavages of alpha-chain. These are all acidic residues and include the Glu-736/Glu-737 pair, Glu-747, and the Glu-754/Asp-755 pairing. The second class affects only the ability of sCR1 to be a cofactor for the third factor I cleavage and include Glu-744 and the Lys-757/Glu-758 pairing. The dominance of acidic residues in the loss-of-function mutants is striking and suggests that H and CR1 contribute basic residues to the interface. Additionally, although there is partial overlap, the contacts required for CR1 binding appear to extend over a wider portion of the 727-767 segment than is the case for factor H. Finally, none of the mutations had any effect on the interaction between soluble MCP and C3(H2O), indicating that despite its functional homology to H and CR1, MCP differs in its mode of binding to C3b/C3(H2O).

Amino Acid Sequence↗
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↗
PubMed1993

Production of complement component C3 in vivo following 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to decrease serum complement C3 levels in female B6C3F1 mice but failed to alter C3 production when added in vitro to either hepatoma cells (both human and mouse hepatoma cells) or mouse primary hepatocytes (Lin and White, 1993a). It has also been demonstrated that mouse liver intracellular C3 levels were not affected following TCDD exposure in vivo, while serum C3 levels were suppressed (Lin and White, 1993b). Therefore, further studies were undertaken to investigate the mechanism by which TCDD modulates newly synthesized serum C3 in vivo. Mouse serum C3 was depleted by an intravenous injection of 50 anti-complement units (ACU)/kg cobra venom factor (CVF). This dose of CVF depleted serum C3 levels to 9% of control at 24 h after treatment. Subsequently, serum C3 levels returned to 19% and 75% of the control level on d 3 and d 5. The recovery of serum C3 was then monitored following an acute oral exposure to 20 micrograms/kg TCDD. In mice exposed to both TCDD and CVF, serum C3 levels reached 15% and 69% of control on d 3 and d 5 after treatment; these results were not significantly different from those of mice treated with CVF alone. Furthermore, when the radiolabeled amino acid [3H]leucine was injected intravenously into either vehicle- or TCDD-treated mice, the incorporation of this labeled precursor into both C3 and other secreted plasma proteins was not inhibited by TCDD. These results demonstrated that TCDD did not decrease newly synthesized C3 in vivo. These studies provide additional support for the concept that TCDD does not act directly on hepatocytes to suppress C3 production. The lower serum C3 levels observed in vivo following TCDD exposure is not the result of a decrease in C3 production by hepatocytes.

Administration, Oral↗
PubMed1997

Purification and characterization of bovine complement component C3 and its cleavage products.

OBJECTIVE: To purify complement component C3 from bovine serum, characterize and analyze NH2-terminal amino acid sequences from its various cleavage products, and do cross-species homology comparisons. ANIMALS: 2 healthy lactating Holstein cows, and 2 healthy adult female New Zealand White rabbits. PROCEDURE: Bovine C3 was isolated from serum, and was cleaved to C3b. The resulting protein was analyzed to determine apparent molecular mass of resulting protein segments. Bands were electroblotted onto a membrane and excised, then NH2-terminal amino acid sequences were determined. RESULTS: The C3 preparation consisted of 6 segments, with molecular mass of 30, 40 (2 bands, a and b), 70, 75, and 115 kd. Via sequence comparisons, the 115-kd band was identified as the alpha chain; the 75-kd segment was determined to be the NH2-terminal portion of alpha chain; the 70-kd piece was identified as the intact beta chain; and the two 40-kd bands are believed to be located at the C-terminal portion of the alpha chain, at the cleavage site that yields C3f. The 30-kd band is the NH2-terminal portion of the alpha chain (minus the C3a segment). Sequence analysis of each band revealed a high degree of homology with human, rat, mouse, and horse C3. Polyclonal antibodies raised in rabbits yielded sera that reacted to the purified sample in manner similar to that of commercially available antibodies. CONCLUSIONS: The purified preparation contained intact C3, C3b, and the degradation products iC3b and C3c, which had high sequence homology with those of other species. The C3a and C3d, and C3g segments of protein were not detected and may have been lost during purification, lyophilization, or transfer steps. Structure and cleavage characteristics of bovine C3 can be used to better understand immune responses to bacterial pathogens in the mammary gland.

Amino Acid Sequence↗
PubMed1984

Chemical characterization of cyanogen bromide fragments from the beta-chain of human complement factor C3.

The isolated beta-chain of human complement factor C3 (C3 beta) was fragmented by cyanogen bromide. Nine fragments were defined by gel filtration and high-pressure liquid chromatography, and characterized with respect to their Mr, amino acid composition and N-terminal amino acid sequence. Approx. 30% of the primary structure of C3 beta was determined. Alignment of the 3 N-terminal fragments allowed determination of 61 of the amino terminal residues of C3 beta. This region demonstrated 40% homology with the sequence in the N-terminal segment of the alpha-chain of the cobra venom factor.

Amino Acid Sequence↗
PubMed1987

S protein/vitronectin in chronic liver diseases: correlations with serum cholinesterase, coagulation factor X and complement component C3.

S protein/vitronectin plays an important role as a regulatory component in the terminal steps of the complement- and coagulation cascades. In patients suffering from chronic liver diseases, plasma S protein concentration was measured and compared with changes in serum cholinesterase activity, coagulation factor X activity and complement component C3 concentration. Significant decreases of all these proteins were seen in liver cirrhosis. Changes in S protein concentration correlated closely with those of cholinesterase, factor X and complement C3. The data give support for the liver as the main organ of plasma S protein/vitronectin synthesis.

Adult↗
PubMedDate not supplied

[The pathomorphology of the kidneys in the fetuses of mothers suffering from late gestosis, type-1 diabetes mellitus and chronic glomerulonephritis].

Fetal kidneys from mothers with late gestosis, diabetes mellitus-1 and chronic glomerulonephritis were studied. There were features of the maturation slowing down and some disturbances in differentiation of rental tissue were revealed. Local degenerative, membranous, proliferative and fibroplastic changes with formation of immune complexes including IgM and C3-complement in late gestosis, IgA, G, C3-complement fractions IgG, M, C3-complement fraction and traces of membranous and proliferative alteration were observed in chronic glomerulonephritis, they were less frequent in diabetes mellitus in mothers, and not so often in late gestosis. Activation of collagen production of types I, III, IV and V was most commonly observed in diabetes mellitus, in chronic glomerulonephritis and late gestosis, it being more rare.

Antigen-Antibody Complex↗