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PubMed1980

Immunochemical quantitation of serum complement components in SFD and AFD infants.

Components of complement (protein concentrations of C1q, C3, C3-activator, C4, C5 and C9 and whole complement (hemolytic activity)) were measured in sera from full-term small-for-date (SFD) and appropriate-for-date (AFD) infants and their mothers. (1) Half the SFD infants showed lower C1q levels than the AFD infants. (2) SFD infants showed the same levels of C3 as AFD infants. (3) Although SFD infants showed slightly higher levels of C3-activator than AFD infants, there was no significant difference. (4) SFD infants and AFD infants showed the same level of C4. (5) With respect to C5, half the SFD infants showed lower levels than the AFD infants. (6) Levels of C9 in the SFD infants were essentially the same as those in the AFD infants. (7) The amount of protein in every complement component of an infant was smaller than that of the mother. In AFD infants, the infant-maternal ratios were 0.64 for C1q, 0.45 for C3, 0.29 for C3-activator, 0.43 for C4, 0.54 for C5 and 0.12 for C9. (8) The whole complement titers of umbilical cord sera from the AFD infants were approximately one half of those of the maternal sera. This is due to the smaller amount of complement protein itself in the infant sera. (9) The whole complement titers of umbilical cord serum agreeably correlate with gestational weeks and birth weight of the infants. (10) The whole complement titer in full-term SFD infants was lower than that in normal full-term AFD infants.

Complement C1↗
PubMed1993

Perioperative alterations in polymorphonuclear leukocyte function of gastrointestinal surgery.

To characterize the alteration of perioperative polymorphonuclear leukocytes (PMNs) function in surgical stress, we studied twenty six patients undergoing gastrointestinal surgery. Seventeen patients with thoracic esophageal cancer underwent total thoracic esophagectomy through a right thoracotomy (severe surgical stress group). Nine patients underwent cholecystectomy (slight surgical stress group). Phagocytic oxygen-dependent microbicidal activity in the esophagectomy patients significantly increased postoperatively, by measuring O2- production (35.3 +/- 7.0 nmol/10(6) cells/ml/20 min on postoperative day 1 vs. 28.6 +/- 6.2 preoperatively, p < 0.01) and luminol-dependent chemiluminescence (99.5 +/- 29.9 x 10(5) cpm/10(5) cells on postoperative day 3 vs. 67.5 +/- 12.8 preoperatively, p < 0.01). On the other hand, only a slight change was seen in the cholecystectomy patients. We conclude that the postoperative PMN function in terms of oxygen-dependent microbicidal activity significantly increases when the degree of surgical stress is sufficient. In order to gain insight into the mechanism of PMN activation, we specifically analyzed the expression of complement receptors. Up-regulation of complement receptors were seen in the esophagectomy patients, which parallels the activation of PMN microbicidal activities. It was suggested that phagocytic PMN function in severe surgical stress significantly increases postoperatively, in part, based on the upregulation of cell surface complement receptors.

Blood Bactericidal Activity↗
PubMed1981

Disruption of complement-mediated reactions by insoluble dentifrice ingredients.

It has been strongly suggested that the complement system plays a critical role in the pathological processes occurring in periodontal disease. Because individuals with this common disease are often instructed to brush their teeth more often and for longer periods of time, several commercial toothpastes were tested for their effects on complement-mediated reactions. In this study, six of the nine toothpastes tested activated the classical complement pathway, leading to C3 cleavage, as determined by crossed immunoelectrophoresis. The activating ingredients were contained in the insoluble fraction of the toothpastes. Of the toothpaste abrasives, Ca++ pyrophosphate was determined to have C3-converting activity. One of the toothpastes, which contains a particular type of amorphous silica abrasive, appeared to bind both native C3 and its conversion products. In general, disruption of complement-mediated functions in affected tissues could alter local immunological responses and interfere with healing. The in vitro studies described here suggest a need for clinical studies to ascertain the in vivo influences of dentifrice ingredients on complement-mediated reactions in periodontal disease.

Complement Activation↗
PubMedDate not supplied

Complete Clq deficiency associated with IgG multiple myeloma.

We report a case of IgG multiple myeloma with selective complete Clq deficiency. The patient was a 75-year-old Japanese woman who exhibited urticaria on the arm and an absence of serum hemolytic complement activity (CH50). Further studies revealed no vasculitis in the urticarial lesion but showed selective complete deficiency of Clq without low molecular weight Clq precipitin. Addition of highly purified Clq restored the CH50 level of the patient's serum to normal. It is suggested that this abnormality was a primary Clq deficiency. We discussed a relationship between the Clq deficiency and myeloma and reviewed the literature.

Aged↗
PubMed1987

Deposits of immunoglobulins, complement, and immune complexes in inflamed human gingiva.

Gingival biopsy specimens from 20 patients with moderate to advanced periodontitis were obtained from inflamed sites with pockets of 5 mm or more. Sections were studied by an immunofluorescence technique, using polyclonal rabbit or goat anti-IgG, anti-IgM, anti-C1q, anti-C3a, and anti-C3c and mouse monoclonal anti-C9. Prewashed ethanol-fixed and nonwashed ethanol-fixed or frozen specimens showed many plasma cells staining for IgG or C3a, suggesting the possible occurrence of a receptor for C3a in plasma cells. Plasma cells containing IgM were also seen. Deposits of IgG and IgM with C1q, C3a, and C3c, suggesting immune complexes, were demonstrated by a double staining technique, combining fluorescein (FITC) or rhodamine (TRITC)-labeled anti-immunoglobulins with TRITC- or FITC-conjugated antibody to C3a, C3c, and C1q. The complexes were located mainly within or around vessel walls. Deposits of C3a and C1q were found in vessel walls, in the basement membrane zone of oral gingival epithelium, or diffusely distributed in the tissues. Deposits of C3c were found to a lesser extent and only in vessel walls. Mouse monoclonal anti-C9, visualized with FITC-labeled rabbit anti-mouse and swine anti-rabbit antiserum, showed granular deposits of C9, mainly in the basement membrane zone of oral gingival epithelium. The study indicates the involvement of immune complex vasculitis in inflammatory periodontal lesions. Also, our observations of the occurrence of deposits of complement factors support the hypothesis that complement factors play an important role in the immunopathology of the periodontal lesion.

Antigen-Antibody Complex↗
PubMed1988

Immunocytochemical analysis of contact lens surface deposits in transmission electron microscopy.

We studied 8 soft contact lenses from asymptomatic wearers by means of an immunocytochemical method, in transmission electron microscopy. In particular, the presence of IgA, IgG, IgE, Clq complement fraction within the surface deposits was analyzed. All the lenses were found positive for the immunoglobulins and the Clq, being the tarsal side more heavily coated than the corneal one. IgA was the predominant Ig, followed by IgG, IgE, and Clq in this descending order. New, never worn lenses were found completely negative for any of the proteins under investigation. We conclude that the Igs come from the tear fluid and speculate about the Clq as a possible sign of involvement of the host immuno-defense mechanism against the prosthesis.

Adult↗
PubMed1980

An evaluation of two methods for detection of circulating immune complexes in patients with rheumatoid arthritis.

Immune complexes were detected by Clq-binding activity (Clq-BA) in 58% of 107 patients with seropositive rheumatoid arthritis (RA), and in 24% of 31 patients with seronegative arthritis. The difference is significant. Immune complexes were detected by the anticomplementarity test (AC) in approximately half of the patients without significant inter-group differences. No correlation was observed between the two methods. In 35 randomly selected patients with seropositive RA, a significant correlation was observed between Clq-BA and the functional class and the latex titre for rheumatoid factor. In patients with seronegative RA, the Clq-BA was significantly correlated to the number of joints with impaired mobility. The AC test was correlated to the erythrocyte sedimentation rate and the concentration of hemoglobin and gammaglobulin in patients with seropositive RA. As regards the clinical activity of disease, erythrocyte sedimentation rate and hemoglobin seem better parameters than the Clq-BA and AC tests.

Antigen-Antibody Complex↗
PubMed1995

Genetic deficiencies of complement.

Genetic deficiencies of proteins of the complement system are associated with diverse clinical phenotypes. These clinical manifestations vary as a function of the specific component that is missing. Molecular and cellular biological methods, coupled with more intensive clinical studies, have defined the pathophysiological basis for this set of genetic disorders. Insights into the normal function of complement and its role in immunopathology have been derived from the extensive work in this field during the past few years.

Complement C1↗
PubMed1977

Complement receptors and cell associated complement components.

Membrane receptors for activated complement components are widely distributed amongst tissue cells of most mammalian species. Common amongst these are receptors for C3b which mediate many of the biological functions of C3. In addition, the genetic control of certain complement components is linked to the genes which code for the major histocompatibility complex. Many of these components are also present on cell surfaces. This suggests that the function of the complement system and the major histocompatibility complex may be related.

Animals↗
PubMed1993

Genetic deficiencies of the complement system and association with disease--early components.

Genetic deficiency of one of the early components of the classical pathway of complement (C1q, C1r, C1s, C4 and C2) is often associated with clinical symptoms and immunochemical abnormalities common in idiopathic autoimmune diseases, such as lupus erythematosus, but also with an increased incidence of various, local and generalized infections. These observations are consistent with the current view of the complement system's role in handling immune complexes and combating microbial invasion. However, the absence of absolute correlations in these experiments of nature suggests that genetic defects of the classical pathway act only epistatically to other host factors and the primary etiologies of the associated diseases. In contrast, the strong association of properdin and factor D deficiency with serious infections caused by encapsulated Gram-negative bacteria suggests a more immediate involvement of the alternative pathway in a specific segment of immunity and its pathology. This concept is also supported by the primordial role of the alternative pathway in the evolution of the complement system and the apparent lethality of factor B deficiency. The gene structures of most of these early components have now been elucidated providing the basis for detailed analyses of the defective alleles, the determination of carrier status, and prenatal diagnosis.

Complement C1↗
PubMed1976

Plasma concentrations of connective tissue compounds: I. the effect of uterine involution.

The information obtained in a prospective study of plasma concentrations of connective tissue components during the third trimester of pregnancy, 4 days, and again at 6 weeks postpartum, suggests that the increased concentrations of plasma protein-hydroxyproline (hypro-protein), free proline, and GAG are associated with increased rate of hydrolysis of extraskeletal connective tissue components.

Adolescent↗
PubMed2000

Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19.

Mannan-binding lectin (MBL) and C1q activate the complement cascade via attached serine proteases. The proteases C1r and C1s were initially discovered in a complex with C1q, whereas the MBL-associated serine proteases 1 and 2 (MASP-1 and -2) were discovered in a complex with MBL. There is controversy as to whether MBL can utilize C1r and C1s or, inversely, whether C1q can utilize MASP-1 and 2. Serum deficient in C1r produced no complement activation in IgG-coated microwells, whereas activation was seen in mannan-coated microwells. In serum, C1r and C1s were found to be associated only with C1q, whereas MASP-1, MASP-2, and a third protein, MAp19 (19-kDa MBL-associated protein), were found to be associated only with MBL. The bulk of MASP-1 and MAp19 was found in association with each other and was not bound to MBL or MASP-2. The interactions of MASP-1, MASP-2, and MAp19 with MBL differ from those of C1r and C1s with C1q in that both high salt concentrations and calcium chelation (EDTA) are required to fully dissociate the MASPs or MAp19 from MBL. In the presence of calcium, most of the MASP-1, MASP-2, and MAp19 emerged on gel-permeation chromatography as large complexes that were not associated with MBL, whereas in the presence of EDTA most of these components formed smaller complexes. Over 95% of the total MASPs and MAp19 found in serum are not complexed with MBL.

Calcium↗
PubMed1977

NIH conference. Pathophysiology of immune hemolytic anemia.

Studies of the pathophysiology of autoimmune hemolytic anemia emphasize the important role of cell membrane receptors for various immunologically active proteins in the clearance of foreign or damaged particulate materials from the blood stream. Receptors for the Fc fragment of immunoglobulin G (IgG) antibodies and for opsonically active fragments of the third component of complement on cells of the reticuloendothelial system function to clear from the circulation erythrocytes coated with these proteins. Our studies show the key role that complement plays in the biologic function of immunoglobulin M (IgM) antibodies like many cold agglutinins and isoagglutinins. They show how complement may contribute to IgG-mediated cell destruction. The IgG and IgM antibodies have dramatically different effects on erythrocyte survival, and these effects explain many of the clinical differences between IgG- and IgM-mediated hemolytic diseases. These studies also show that many of the factors that influence the course of autoimmune hemolytic anemia act by altering the level of immunologic sensitization required to mediate clearance.

Agglutinins↗
PubMed1978

Clinical and antibody responses after influenza immunization in systemic lupus erythematosus.

After immunization with A/New Jersey/76 and A/Victoria/75 influenza vaccines, 11 patients with systemic lupud erythematosus were serially evaluated for changes in disease activity, serologic abnormalities, and their capability to generate specific antibodies. One patient, with active disease, developed a diffuse, proliferative glomerulonephritis. None of the other patients or control subjects had significant local or systemic side effects. Significant levels of antibodies were generated to A/New Jersey/76 in eight of the 11 patients and in seven of eight control subjects and to A/Victoria/75 in seven of 11 patients and five of eight control subjects. The geometric mean responses of both total and IgG antibodies to each viral antigen were no different in patients with systemic lupus erythematosus than in control subjects. In patients with stable systemic lupus erythematosus, immunization with killed influenza viral vaccine appears to be safe and effective.

Adolescent↗
PubMed1979

Sjögren's syndrome: a defect in reticuloendothelial system Fc-receptor-specific clearance.

To determine the functional status of reticuloendothelial system Fc receptors in patients with Sjögren's syndrome, we studied the rate of clearance from the circulation of 51Cr-labeled IgG-sensitized autologous erythrocytes in 19 patients. Fc-receptor-mediated clearance was abnormal in 12 of the 19 patients, with half-lives ranging from 80 to 356 min. There was a significant correlation between clearance rates and clinical manifestations of disease. Clearance rates tended to be normal in patients with disease limited to exocrine glands and abnormal in patients with widespread disease. In contrast, there were no correlations between the rate of clearance of IgG-sensitized erythrocytes and serum immune complex levels, serum complement component levels, or rheumatoid factor titers. The striking correlation between clearance rates and disease manifestations suggests that decreased clearance of immune complexes by defective reticuloendothelial system Fc receptors may contribute to disease pathogenesis.

Adult↗
PubMed1981

Lupus erythematosus-like syndrome with selective complete deficiency of C1q.

A 37-year-old Japanese man in previously good health was hospitalized because of swelling of the auricles had discoid erythema of the face. Clinical and laboratory findings satisfied the diagnostic criteria for systemic lupus erythematosus proposed by the American Rheumatism Association. However, serologic studies showed weakly positive antinuclear factor and absence of anti-DNA antibody and lupus erythematosus cells. A striking abnormality was the total absence of serum hemolytic complement activity (CH50). Further studies showed selective complete deficiency of C1q, a subunit of the first component of complement (C1). This is the first reported case of lupus erythematosus-like syndrome with selective complete deficiency of C1q.

Adult↗
PubMed1976

Immune complexes and complement hypercatabolism in patients with leprosy.

The occurrence of immune complexes in the serum and the level of the C3 breakdown product C3d in the plasma from patients with leprosy were studied by quantitative methods and the results were compared in various forms of the disease. These studies were performed on sixty-two samples from twenty-six patients. The serum 125I-C1q binding activity was found to be increased by more than 2 s.d., as compared to the normal values, in most of the sera from patients with erythema nodosum leprosum (ENL) (80%) and uncomplicated lepromatous leprosy (82%), but also in the sera from patients with tuberculoid leprosy (58%). In vitro studies suggested that immune complexes involving mycobacterial antigens were present in leprosy sera. An increased C3d level (greater than 2s.d.) was also found in most of the plasma from patients with ENL (70%), but rarely in the plasma from patients with uncomplicated lepromatous leprosy (18%) and never in tuberculoid leprosy patients' plasma. The absence of a significant correlation between the 125I-C1q binding activity and the C3d level in leprosy patients may suggest that extravascular immune complexes are involved in the complement activation occurring in ENL. The quantitation of C3d in plasma may be of some practical interest in the early diagnosis of ENL complications of leprosy.

Adult↗