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PubMed1981

Familial C1q deficiency in 3 siblings with glomerulonephritis and Rothmund-Thomson syndrome.

Complete absence of C1q was demonstrated in the sera of 3 siblings in association with renal and cutaneous lesions. The serologic findings were consistent with an autoimmune disorder. Hematuria was the renal symptom present in all 3 patients; proteinuria was also present in 1. Renal biopsies showed mesangial proliferative glomerulonephritis with diffuse glomerular deposits of IgM and C3 in all cases. Clinical cutaneous manifestations and the histological picture were those of the Rothmund-Thompson syndrome. Three combined diseases, characterized by renal and cutaneous affection and serologic abnormalities, are presented in this paper.

Basement Membrane↗
PubMed1988

Glomerular annular-tubular immune deposits in adult hemolytic uremic syndrome.

An 82-year-old female developed hemolytic uremic syndrome (HUS) after a prodromal illness of bloody diarrhea. No specific enteric pathogen was isolated. A renal biopsy performed 5 days after the onset of azotemia revealed typical thrombotic microangiopathy. By electron microscopy, massive annular-tubular deposits admixed with fibrillar fibrin were demonstrated in glomerular capillaries. Immunofluorescent staining of the intracapillary material was positive for IgG, IgM, C3, C1q and fibrin-related antigens. No evidence of plasma cell dyscrasia, cryoglobulinemia or systemic lupus erythematosus was found, and the patient recovered renal function uneventfully in 2 months. Organized immune deposits appear to have played a role in the pathogenesis of HUS in this patient.

Aged↗
PubMed1975

Effects of anesthesia, surgery and inflammation upon host defense mechanisms. I. Effects upon the complement system.

Complement protein levels and C7 hemolytic activity were measured in four individuals following anesthesia and surgery, and in a group of 20 patients with inflammatory diseases. Seven of the eight complement components studied characteristically were elevated, most dramatically C1s and C3PA. Elevation of C1s often was greater than elevation of C1q, displaying an independent variation of C1s and C1q in both postoperative and inflammatory disease patient groupds. The major increases of C components were seen subsequent to the peak C-reactive protein response, as was the occurrence of the 'reactor state', a propensity to formation of C56 which surprisingly was associated with increased levels of C7. Levels of properdin frequently were reduced postoperatively. It is concluded that multiple complement components, with the notable exception of properdin, respond as acute phase reactants which are elevated and changed in proportion postoperatively and during inflammatory disease.

Anesthesia, General↗
PubMed1976

The inactivator of the first component of human complement (C1INA): the complex formation with plasmin.

The reaction of C1INA with plasmin was followed by the stoichiometric inactivation of both activities. On acrylamide gel electrophoresis, the reaction mixture revealed 3 new substances. One formed a precipitin band against anti-C1INA and its molecular weight was 103,000 daltons, 14,000 less than that of C1INA, indicating that a portion of C1INA was partially cleaved by the proteolytic activity of plasmin. Each of the other two substances formed precipitin bands against anti-C1INA as well as against anti-plasminogen. Molecular weights of these two substances were 200,000 and 179,000 daltons, whereas the molecular weights of C1INA and plasmin are 117,000 and 82,000 daltons, respectively. From these results, it was concluded that a portion of C1INA in the reaction mixture was partially cleaved by plasmin, and the partially cleaved C1INA as well as the native C1INA form 1:1 molecular complexes with plasmin, leading to inactivation of these activities.

Animals↗
PubMed1976

A case of unusual SLE related syndrome characterized by erythema multiforme, angioneurotic edema, marked hypocomplementemia, and Clq precipitins of the low molecular weight type.

Our patient and those of Agnello et al. had identical clinical symptoms such as erythema multiforme, arthralgias and angioneurotic edema and both differed from systemic lupus erthematosus in several important points, i.e., in spite of marked hypocomplementemia the nephropathy is not prominent and it needs high-dose steroids to eliminate the clinical and serological abnormalities. In addition to the features reported by Agnello et al. we found increased viral antibody titers in our patient's sera.

Adult↗
PubMed1979

Inhibition of the interaction between the complement component Clq and immune complexes.

Several groups of compounds were examined for their ability to inhibit in vitro the binding of Clq to insoluble immune complexes. As expected from previous studies, polyinosinic acid, liquoid, sodium pentosan polysulfate, aliphatic diamines and heparin are good inhibitors. This study shows that compounds with much lower toxicity, such as certain amino acids and substances with vitamin B6 activity (pyridoxal-5-phosphate:P5P) were also capable of decreasing the binding of Clq. Using methods of equilibrium dialysis and difference spectra, it was shown that this compound binds to both, Clq und IgG antibody by forming Schiff bases. Clq binds approximately 10 times more P5P when compared to IgG. Immune complexes prepared with IgG antibody modified by P5P and stabilized with sodium borohydride had the same complement-fixing and Clq-binding capacity as normal immune complexes. This suggests that the inhibition of Clq-binding to immune complexes by P5P is due to a modification of lysyl resides in Clq. Collagen and IgG fragments derived from Fc were also found to inhibit Clq binding to immune complexes, but at higher concentrations than the above small-molecular compounds and with a different mode of action.

Animals↗
PubMed1979

Impairment of acute protein reactivity in chronic renal failure.

The acute phase protein response was studied after elective surgery in 13 normal subjects and 9 patients with severe chronic renal failure. Total haemolytic complement reactivity (CH50) and serum concentrations of C1q, C1s, C4, C3, factor B, properdin, C5, C9, C-reactive protein (CRP), caeruloplasmin, alpha1-acid glycoprotein and haptoglobin were measured preoperatively and on days 2, 4 and 6 after operation. Abnormalities were seen in the group with chronic renal failure. Firstly, there was no significant acute phase response of C1s, C3, C5, C9 and CH50 and a significant reduction in the response of factor B. Secondly, CRP showed prolonged elevation in the post-operative period in contrast to the transient rise seen in the control group. With the possible exception of alpha1-acid glycoprotein, the behaviour of the non-complement proteins (caeruloplasmin and haptoglobin) was comparable for the two groups. These defects could impair the physiological response to infection in patients with severe chronic renal failure.

Adult↗
PubMed1979

Complement profiles in monkeys subjected to aggregate (immune complex) anaphylaxis, and following injection of soluble and particulate polysaccharides.

Complement profiles were established in four groups of Macaca irus monkeys: (I) Aggregate (immune complex) anaphylaxis was induced following immunization, with ovalbumin. Upon challenge, systemic arterial pressure decreased from 115 to 50 mm Hg (mean values) in 10 min. The complement profiles revealed decreases in: C1q to less than 10% of initial value within 5 min; C4 proportional to hypotension; C3 slowly to 60% at 24 h; C5, C6, C7, C8 and factor B to about 80% of initial value in 5--30 min. Conversion products of C3 and factor B were detected on the day of anaphylaxis. In conclusion, mainly the classical and to a lesser extent the alternative pathway, were activated. Following injection of (II) native B 512 dextran, (III) biodegradable starch microspheres, and (IV) saline, no significant changes of complement profiles were seen. Conversion products of C3 and factor B were, however, demonstrable in groups II and III without appearance of clinical signs.

Anaphylaxis↗
PubMed1980

Asbestosis and systemic lupus erythematosus.

A case associating asbestosis and clinical lupus erythematosus (SLE), both diagnosed according to standard criteria, is described. It is suggested that such an association may bear some analogy to the well-known 'Caplan-Collinet' syndrome, associating silicosis and rheumatoid arthritis.

Adult↗
PubMed1980

Nonparticipation of C1q in the decrease of complement activity in the cold in sera of patients with chronic liver diseases.

Serum and plasma samples taken simultaneously from 560 patients with various diseases were examined for hemolytic complement activity (CH50) after incubation at 4 degrees C for 20 h. Serum CH50 titers less than 20 U/ml were observed in 39 cases and among them, a difference between serum and plasma CH50 of more than 5 U/ml were observed in 16 cases. Diagnosis of most of them were chronic liver diseases. To analyze the dissociation of CH50 titers between serum and plasma, sequential estimations of CH50 were performed on serum and plasma samples which showed the dissocation incubated at 4 and 37 degrees C. Marked decrease in CH50 titers was obtained in sera but not in plasma incubated at 4 degrees C. In such sera, however, no significant decrease of protein amount and agglutinating activity of C1q was observed. The result could indicate that C1q would not participate in the decrease of serum hemolytic activity in the cold, suggesting an activation of complement other than the classical pathway.

Antigen-Antibody Complex↗
PubMed1988

Complement subcomponent C1q in various strains of mice. Its serum content correlates with that of immunoglobulin G.

The protein amount and the hemolytic activity of the initiating complement component (C1q) in the classical pathway, and the level of immunoglobulin G (IgG) in sera of various inbred mouse strains were measured in parallel with those in sera of closed colony mice. C1q levels were significantly high in male A/He and C57BL/10Sn mice, and conspicuously high in female C57BL/10Sn mice. In these strains and C57BL/6J mice of both sexes, IgG levels were also significantly high. IgG levels were strikingly high in female NZB mice and NZW mice of both sexes. On the other hand, both C1q and IgG levels were conspicuously low in BALB/c mice of both sexes and in male CBA mice, and surprisingly low in BALB/c-nu (nude) mice of both sexes. A significant correlation was observed between serum levels of C1q and IgG. The C1q specific activity, however, was equivalent in all serum samples with approximately 2 x 10(13) effective molecules/mg. The subunit composition of C1q analyzed by polyacrylamide gel electrophoresis was well comparable within all strains of mice tested. These results may suggest that mouse serum C1q does not have any phenotypic polymorphism.

Animals↗
PubMed1988

Discrepancy between effects of in vivo and in vitro administration of gammaglobulin on phagocytic killing of Streptococcus pneumoniae in an antibody-deficient serum.

Phagocytic killing of Streptococcus pneumoniae serotypes 6A, 14, 18C, 19F and 23F was investigated in the dysgammaglobulinemic serum of a patient with recurrent pneumococcal infections. Previous studies with this serum had established combined IgG2, IgG4 and IgA deficiency, deficiency with regard to specific antipolysaccharide antibodies and essentially normal complement functions. Phagocytic killing of all serotypes was reduced in the patient's serum. Addition of immunoglobulin in vitro enhanced both classical and alternative complement pathway mediated opsonization. In constitution experiments neither purified Clq nor CRP influenced phagocytic killing. Surprisingly, intramuscular administration of a fairly small dose of gammaglobulin to the patient was associated with a rapid increase in the serum opsonic activity for serotype 23F. The increased opsonization occurred before specific anticapsular antibodies were detectable in serum. The findings suggest that the possible effects of gammaglobulin treatment may not exclusively be related to the acquisition of serotype-specific antibodies.

Complement Activating Enzymes↗
PubMed1987

Immune complexes and complement components in Bell's palsy.

The serum levels of circulating immune complexes were studied in 63 patients and the complement system in 36 patients with Bell's palsy. The IgG-C1q and IgG-C3 containing immune complexes were analyzed by an enzyme-linked immunosorbent assay. The levels were found to be significantly elevated in the acute and convalescent stages of the palsy compared with controls. The total complement activity as determined by a CH50 assay and complement component C3 titrations also showed elevated values. The levels of C2 were not altered. The results indicate in Bell's palsy an inflammatory process and an antigen-antibody response which may be triggered by a viral antigen.

Adolescent↗
PubMed1977

On the age-associated presence of immunoglobulin and complement in the renal glomeruli of mice.

Immunofluorescence studies revealed the age-associated presence of mouse IgG, with or without beta1 C in renal glomeruli of various strains of laboratory mice. These were classified into two types: (1) IgG demonstrated without beta1 C and the fluorescence of which was easily decreased by prewashing with PBS. (2) IgG demonstrated almost always with beta1 C and the fluorescence of which remained unchanged by prewashing with PBS. The deposition of immunoglobulin seems to be closely connected with the immune state of animals including the phagocytic function of the mesangium.

Aging↗
PubMed1989

Monoclonal antibodies against components of the classical pathway of complement.

Activation of the classical pathway of complement involves several binding and enzymatic cleavage processes. Binding and enzymatic activation results in the appearance of new structures in the individual components. This report describes the different activation steps for C1q, C1r, C1s, C4 and C2 and summarizes monoclonal antibodies reported so far which recognize either conserved epitopes or activation-dependent epitopes with particular emphasis on neoepitopes occurring during the activation cascade.

Antibodies, Monoclonal↗
PubMed1989

Neoepitopes expressed by immune complexes.

The impact of antibodies or other reagents selectively reacting with neoepitopes expressed by immune complexes (IC) upon the detection and isolation of IC is reviewed. Immunoglobulin, C1q and C3 are the three components which have been most utilised for the non-specific detection of IC. Particularly C3 of these three proteins is known to express neoepitopes which arise after enzymatic cleavage of the native C3 molecule. There are several monoclonal antibodies (MoAbs) which recognise these neoepitopes and their use renders IC assays and isolation both easier and less prone to spurious interactions and interference. Furthermore these MoAbs recognise neoepitopes arising at different stages of C3 degradation which may allow analysis of the human in vivo metabolism and processing of C3 bound to IC.

Antibodies, Monoclonal↗