Human diseases associated with C3 receptor deficiencies.

Genetic deficiencies of complement receptors have recently been described. CR1 expression is reduced on erythrocytes, leucocytes and podocytes of many patients with systemic lupus erythematosus because of both genetic and acquired mechanisms. CR1 deficiency is also found in AIDS and AIDS-related syndromes and correlates with clinical subpopulations of HIV-infected patients.

Recovery from anti-VIII:C (antihemophilic factor) autoimmune disease is dependent on generation of antiidiotypes against anti-VIII:C autoantibodies.

Plasma samples obtained from a patient 6 wk, 6 months, and 4 yr after recovery from anti-VIII:C (anti-hemophilic factor, where VIII:C = factor VIII procoagulant activity) autoimmune disease were found to contain antibodies that inhibited anti-VIII:C activity in the patient's prerecovery plasma and in the plasma of two other patients with anti-VIII:C autoantibodies. F(ab')2 fragments from postrecovery IgG suppressed anti-VIII:C activity in F(ab')2 fragments from prerecovery IgG within a narrow range of molar ratios. Anti-VIII:C activity in F(ab')2 autoantibodies was also inhibited by F(ab')2 fragments from polyspecific therapeutic immunoglobulins prepared from a large pool of normal donors (IVIg).

Bartter's syndrome with normal chloride reabsorption during indomethacin treatment.

A 17-year-old male patient with Bartter's syndrome was admitted for renal function studies. This patient had persistent hypokalemia, first found at age 5; the diagnosis of Bartter's syndrome with renal hypersecretion of prostaglandins E2 and F2 alpha had been established at age 13. A congenital defect of chloride reabsorption was expected, but after 4 years of indomethacin treatment no such defect was found.

Immunohistochemical analysis of C3 cleavage fragments, factor H, and the C5b-9 terminal complex of complement in de novo membranous glomerulonephritis occurring in patients with renal transplant.

Fifteen renal biopsies from 13 transplanted patients with de novo membranous nephropathy (DNMN) were investigated by immunofluorescence for the presence of C5b-9 neoantigens of the terminal sequence of complement and for antigens expressed by C3 cleavage fragments. DNMN lesions were classified as stage I, II or III upon light and electron microscopy examination. Seven biopsies were classified as stage I DNMN and 8 stage II-III.

Immunohistochemical study of the C5b-9 complex of complement in human kidneys.

The presence and localization of the C5b-9 neoantigens of the terminal complement sequence, of antigens expressed by cleavage fragments of C3, and of Factor H antigens have been studied by immunohistochemical techniques in morphologically normal adult human kidneys and in biopsy specimens from patients with a wide range of renal diseases with and without immune deposits. In morphologically normal kidneys, C5b-9 neoantigens were observed within all connective matrices (arteriolar media, glomerular basement membrane (GBM), mesangial matrix and tubular basement membrane). The C3d and C3g antigens of the C3dg, and C3bi cleavage fragments of C3 and Factor H antigens were found in similar locations.

15-HETE "modulates" expression of C3b receptor (CR1) antigen on peripheral blood B-lymphocytes.

We have studied the effect of the lipoxygenase metabolite, 15-HETE, on the expression of the human C3b receptor (CR1) by a B-lymphocyte enriched population of human peripheral blood leukocytes. The number of CR1 antigenic sites expressed by B-lymphocytes isolated from HLA typed donors was determined by equilibrium binding studies using an 125 I-labelled mouse monoclonal anti CR1 antibody before and after 16 hrs incubation in RPMI alone or containing 10(-6)M, 10(-7)M or 10(-8)M final concentration of 15-HETE. In B44- subjects CR1 expression on B cells increased 63% after incubation in RPMI alone.

Characterization of monoclonal antihuman-B-cell antibody BL13 as an anti-C3d-receptor (CR2) antibody.

BL13, a mouse monoclonal IgG1 antibody raised against human B cells, blocked the function of the C3d receptor (CR2) and bound with high affinity (5 X 10(8) L M-1) to CR2 on B lymphoma cells. Following capping with the second antibody, BL13 inhibited C3d-dependent rosette formation of Daudi and Raji cells and C3b-dependent CR2-mediated rosette formation with B lymphoma cells, but did not inhibit CR1-mediated rosettes between C3b-bearing cells and peripheral blood lymphocytes. Competitive binding experiments between biotinylated BL13 or anti-CR2 antibody HB-5 and unlabelled antibodies demonstrated that BL13 bound to an epitope that is distinct from that recognized by HB-5, and closely associated with that recognized by monoclonal antibody anti-B2.

Characterization of the human glomerular C3 receptor as the C3b/C4b complement type one (CR1) receptor.

The functional and immunochemical characteristics of the human glomerular C3 receptor were investigated by adherence of sheep erythrocytes (Es) coated with defined C3 fragments and by using polyclonal and/or monoclonal antibodies directed against epitopes expressed on complement receptors CR1, CR2, and CR3. C3b-bearing Es (EsC3b) strongly adhered to glomeruli in frozen kidney sections in a reaction that was selectively inhibited by F(ab')2 anti-CR1 antibodies. There was no adherence of EsC3dg, EsC3d, and EsC3bi in the presence or absence of Ca++ and Mg++ under physiologic buffer conditions.

Human eosinophils express CR1 and CR3 complement receptors for cleavage fragments of C3.

The functional and antigenic characteristics of C3 receptors expressed on human eosinophils were investigated using rosette assays with sheep erythrocytes coated with C3 fragments and flow cytometric analysis of cells stained with anti-receptor antibodies. Purified peripheral blood eosinophils from 13 patients with hypereosinophilia expressed CR1 antigens. In 8 patients, a mean of 14 + 9.

Decreased expression of C3b receptor (CR1) on erythrocytes of patients with systemic lupus erythematosus contrasts with its normal expression in other systemic diseases and does not correlate with the occurrence or severity of SLE nephritis.

Expression of the C3b/C4b receptor (CR1) on erythrocytes is decreased in patients with systemic lupus erythematosus (SLE) compared to normal individuals, and the CR1 antigen is absent from podocytes in severe diffuse proliferate nephritis of SLE. In the present study, we examined the relationship between the number of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes in non-SLE nephritis and other systemic inflammatory diseases by measuring the binding of 125I-labeled rabbit F(ab')2 and murine monoclonal IgG anti-CR1 antibodies to erythrocytes of normal individuals and patients in a French population. The number of binding sites for monoclonal anti-CR1 antibody on erythrocytes of 116 normal individuals was 743 +/- 22 (mean +/- SEM) with a range of 169-1,333, and the frequency distribution of this number in the population was bimodal.

Anti-C3b-receptor (CR1) antibodies in patients with systemic lupus erythematosus.

Using an enzyme-linked immunoadsorbent assay, IgG in the plasma and purified IgG from 2 patients with systemic lupus erythematosus (SLE) were found to strongly react with purified C3b receptor (CR1) insolubilized on microtiter plates. The amount of IgG that bound to CR1 in 201 plasma samples from 179 other patients with SLE did not significantly differ from that which bound in 72 control samples from normal individuals. Purified IgG from the patients with anti-CR1 reactivity did not inhibit CR1 function in vitro.

[Homozygotic C5 deficiency disclosed by purulent Neisseria meningitidis meningitis].

The complement system functions to protect the individual against infectious agents. Deficiencies of the late-acting complement proteins C5-C8 are associated with an increased susceptibility to Neisseria infection. This paper describes a deficiency in C5 in a Caucasoid family from the north of France that was revealed by the occurrence of a N.

Deficiency of the adhesive protein complex lymphocyte function antigen 1, complement receptor type 3, glycoprotein p150,95 in a girl with recurrent bacterial infections. Effects on phagocytic cells and lymphocyte functions.

A patient presenting delayed umbilical cord detachment, severe recurrent bacterial infections, and inability to form pus exhibited a profound defect in the expression of alpha- and beta-chains of the receptor for the C3bi fragment of C3 (CR3), lymphocyte function antigen 1 (LFA-1) molecule, and the p150,95 molecule found on neutrophils, monocytes, and lymphocyte membranes. This was shown by immunofluorescence studies using specific monoclonal antibodies, rosette formation with C3bi-coated erythrocytes, and immunoprecipitation for the LFA-1 complex. These membrane defects were responsible for abnormal phagocytic cell functions including adherence to nylon wool, cell movement, phagocytosis, and opsonized particle-induced oxidative response and for defective natural killer cell activity.

Suboptimal C3b/C3bi deposition and defective yeast opsonization. II. Partial purification and preliminary characterization of an opsonic co-factor able to correct sera with the defect.

Using a correction assay a factor essential for normal deposition of C3 fragments on zymosan was identified in fractions of serum obtained by Sephacryl S-300 gel filtration (eluting between IgG and albumin), preparative Pevikon block electrophoresis (eluting in the beta-region) and DEAE-ion-exchange chromatography (eluting immediately post IgG). Active material was also identified in a commercial preparation of transferrin. A combination of DEAE-ion-exchange chromatography and gel filtration was used to partially purify the co-factor.

Suboptimal C3b/C3bi deposition and defective yeast opsonization. I. Evidence for the absence of essential co-factor activity.

Defective yeast opsonization in sera with no demonstrable abnormality of known complement components is associated with the absence of inactivity of a co-factor which enhances the deposition of C3 fragments (C3b/C3bi) derived from both classical and alternative pathways of complement activation. The factor binds strongly to zymosan at 4 degrees C and loses its biological activity completely when heated for 30 min at 56 degrees C but not when similarly heated at 50 degrees C. Sera with defective deposition of C3 fragments may be readily corrected with small quantities of sera having normal function.

Ontogenesis of the glomerular C3b receptor (CR1) in fetal human kidney.

Ontogenesis of the glomerular C3b receptor (CR1) was studied in kidneys from 16 fetuses aged from 9 to 32 weeks, using immunohistochemical techniques and the F(ab')2 fragment of a monospecific rabbit antibody to CR1, and adherence of C3b-coated sheep erythrocytes. By indirect immunofluoresence, anti-CR1 stained presumptive glomerular epithelium from the end of the S-body stage of nephron differentiation. Staining increased with visceral epithelial cell proliferation and with differentiation of the nephron from the subcortical to the juxtamedullary part of the fetal kidney.

Human follicular dendritic cells express CR1, CR2, and CR3 complement receptor antigens.

The expression of complement receptors by human follicular dendritic cells (FDC) was investigated by immunohistochemical techniques by using polyclonal and monoclonal antibodies to antigenic determinants of CR1, CR2, and CR3. Upon optical immunohistochemical examination of frozen sections from human reactive lymph nodes and tonsils by a three-step immunoperoxidase technique, a strong staining of cell bodies and cytoplasmic extensions of FDC was observed in germinal centers with anti-CR1 and anti-CR2 antibodies. Staining for these antigens was also found on cytoplasmic extensions of FDC in the mantle zone and on the plasma membrane of B cells in the entire follicles.

Deleterious effects of cardiopulmonary bypass. A prospective study of bubble versus membrane oxygenation.

A number of hematologic and immunologic parameters that reflect erythrocyte and platelet damage and host defense mechanisms against infection were studied in 20 patients undergoing cardiopulmonary bypass during coronary operations. The patients were randomly assigned to a group in which a bubble oxygenator or a hollow-fiber membrane oxygenator was used. Hemolysis, thrombocytopenia, and significant release of beta thromboglobulin occurred in patients from the bubble oxygenator group and, to much lesser extent, in patients from the membrane oxygenator group.

Mouse monoclonal antibodies to the human C3b receptor.

Mouse monoclonal antibodies were raised against the human C3b receptor (CR1) molecule that had been purified from solubilized erythrocytes membranes. Four hybridomas were selected, cloned and expanded because their supernatants reacted strongly with insolubilized CR1 by ELISA and intensely stained B-dependent areas of the spleen and glomerular podocytes by indirect immunofluorescence. The four monoclonal antibodies, named J3D3, J8B10, J3B11 and J7C2, were IgG1 immunoglobulins.

Activation of the human classical complement pathway by a mouse monoclonal hybrid IgG1-2a monovalent anti-TNP antibody bound to TNP-conjugated cells.

A mouse hybridoma selected and cloned for anti-TNP specificity produced three distinct monoclonal antibody species that were separated on protein A-Sepharose by stepwise acid elution. The IgG1 kappa product of the parental myeloma was eluted at pH 6.0.