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[Synovial level of interleukin 1 and C3a in chronic polyarthritis, psoriatic arthritis and activated arthritis].

Concentrations of interleukin-1 (IL-1), C3a des Arg and immune complexes (IC) were investigated in knee effusions of patients with rheumatoid arthritis (RA; n = 36), psoriatic arthritis (Ps.A., n = 19) and osteoarthritis (n = 7). Maximal concentrations of IC and C3a des Arg were found in RA patients, high IL-1-activities could be demonstrated in patients with Ps.A. and seropositive RA. We found significant correlations between IL-1 and C3a des Arg, IL-1 and IC and C3a des Arg, and IC in Ps.A. patients, but not in RA or osteoarthritis patients. The role of IL-1 in the chronic inflammatory response and joint destruction in inflammatory joint diseases is discussed.

Adult↗

Association of levels of circulating C1q binding macromolecules with induction chemotherapy response in head and neck cancer patients.

Ninety-five untreated patients with squamous cell carcinoma of the upper aerodigestive tract expressed significantly higher levels of C1q-binding macromolecules as compared to 45 noncancer-bearing controls. No relationship between C1q-binding macromolecules and levels of circulating IgG-immune complexes as determined by the solid-phase C1q-binding assay or the C3d-solid-phase assay could be defined suggesting that C1q-binding macromolecules were distinct from IgG-circulating immune complexes. An elevated level of C1q-binding macromolecules within these patients was predictive of subsequent response to induction chemotherapy; those with elevated levels characteristically showed no response. Using multivariate logistic regression analysis including the covariates of American Joint Committee staging parameters as well as C1q assay results, levels of the isolated macromolecules added significant prognostic information as to the probability of chemotherapeutic response. The quantitation of C1q macromolecules has clinical implication as to choice of therapeutic regimens against head and neck cancer. The nature of these substances remains to be defined.

Adult↗

Circulating immune complexes in systemic lupus erythematosus: a reappraisal of the solid phase C1q radioimmunoassay.

Data from a pool of 150 patients with systemic lupus erythematosus (SLE) were used to evaluate the clinical usefulness and specificity of the solid phase C1q radioimmunoassay (SPC1q RIA) for circulating immune complexes (CIC). We found that the assay results correlated with the severity of lupus nephritis but that they did not adequately reflect or predict disease activity so as to directly influence decisions regarding treatment. In addition, the contribution of non-IC reactants to the assay results was found to be of some concern. Finally, we could not demonstrate the presence of anti-DNA antibodies in CIC from patients with SLE.

Antigen-Antibody Complex↗

Complement fixation by solid phase immune complexes. Reduced capacity in SLE sera.

We describe an ELISA for assessment of complement function based on the capacity of serum to support fixation of complement components to solid phase immune complexes (IC). Microplates were coated with aggregated bovine serum albumin (BSA) followed by rabbit anti-BSA IgG. The solid phase IC were reacted with human serum. The uptake of C3b, C4b and properdin was measured using biotinylated F(ab)2 antibodies to each of the proteins, avidin alkaline phosphatase, and paranitrophenyl phosphate. Serial samples obtained from 15 patients with systemic lupus erythematosus were investigated. Out of 72 sera, 24 showed a reduced capacity to support incorporation of C4b into solid phase IC. Thirty-one of the sera showed low C3b binding and 59 of the sera a reduced uptake of properdin. The incorporation into solid phase IC of C3b and C4b as well as of C3b and properdin were closely correlated at high disease activity. In general, patients with severe disease manifestations showed low values in the uptake assays. Judging from the results obtained by analysis of serial samples, the uptake of C3b, C4b and properdin, complement mediated solubilization of fluid phase IC and the concentrations of C1q binding IC were useful indicators of disease activity in the patients. The concentrations of circulating C4, C3 and properdin varied less consistently according to disease activity. The concentrations of serum properdin were never found to be low, which was in contrast to the finding of reduced properdin uptake by solid phase IC in most of the samples.

Adult↗

[Disorders in humoral defense: clinical aspects, diagnosis and therapy].

Clinical and immunological findings of 5 patients with distinct defects in either humoral immunity or in the complement system are described. The syndromes presented comprise examples of type I dysimmunoglobulinaemia, X-linked agammaglobulinaemia (XLA), familial deficiency of complement factor C1q and a patient with a selective deficiency in the synthesis of antibodies against pneumococcal polysaccharides. The patients with a defect in humoral immunity all showed recurrent bacterial infections of the respiratory tract. The XLA-patient developed a dermatomyositis-like syndrome and ECHO-virus encephalitis. Prior to the development of a SLE-like syndrome the two siblings with C1q deficiency showed recurrent respiratory tract infections, most probably on basis of a defect in the clearance of immune complexes.

Adolescent↗

[Complement system].

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Age Factors↗

The development of a C1q anti-C1q immunoadsorbent for removal of immune complexes from plasma.

An immunoadsorbent based on immobilized C1q has been developed to remove possibly pathogenic immune complexes from plasma deriving from patients suffering from systemic lupus erythematosus or rheumatoid arthritis. Traditional immobilization procedures based on, e.g., cyanogen bromide activation could not be used to produce an efficient adsorbent. However, by using antibodies directed towards C1q as handles for the immobilization of C1q it was possible to make an adsorbent that efficiently bound immune complexes in plasma. The capacity of the C1q anti-C1q adsorbent to bind artificial immune complexes such as aggregated human globulins or immune complexes from various plasma samples was evaluated. Both batch and column experiments were conducted. The typical capacity in batch was about 1 mg immune complexes/ml gel when incubated with patient plasma samples with high titers of immune complexes. Special attention has to be paid to leakage of undesirable components from the adsorbent. It was found that leakage of C1q occurred but it was not more than after covalent immobilization procedures such as cyanogen bromide.

Antigen-Antibody Complex↗

C1q enhances the phagocytosis of Cryptococcus neoformans blastospores by human monocytes.

We investigated whether C1q, a subunit of the first component of C, could modulate human peripheral blood monocyte-mediated phagocytosis of Cryptococcus neoformans (CN). Adherence of monocytes to C1q-coated surfaces induced a significant enhancement of ingestion of CN blastospores that had been opsonized with specific anticapsular IgG (IgG-CN). Additionally, C1q enhanced the monocyte-mediated phagocytosis of CN opsonized with C (CN-absorbed, nonimmune, normal human serum; C-CN). Ingestion of IgG- and C-CN by control and C1q-stimulated monocytes was maximal by 1 h of incubation. The monocyte-mediated enhancement of phagocytosis caused by C1q was paralleled by a proportionate increase in fungicidal activity, an effect which was maximal by 3 h of incubation. Human serum albumin-adherent, control monocytes exhibited only a low level of killing after 3 h of incubation. C1q enhancement was blocked by preincubation of the surfaces with a goat, polyclonal F(ab')2 anti-C1q. This study describes a new cellular function for the cell surface C1q receptor: the enhancement of phagocytosis of a pathogenic organism by monocytes.

Adjuvants, Immunologic↗

[Value of the detection and characterization of circulating immune complexes in rheumatoid arthritis].

The authors analyse the value of research into and identification of immune complexes (IC) in chronic inflammatory rheumatisms (CIR) and in rheumatoid polyarthritis (RP) in 93 patients hospitalise in a Rheumatology Department. Comparative levels of ICs were established simple and quick technique of measuring the 50% haemolytic complement (HC 50) used up by the ICs. The rheumatoid factor (RF) is identified at the PEG IC precipitates with the Waaler-Rose test. The existence of raised levels of IC containing RF in both seropositive and seronegative PRs and to a similar degree in a non-negligable percentage of clinically non-classable RICs conforms the diagnostic value of this research. On the other hand there is no relationship between the levels of ICs and either clinical signs or age of the illness. In RPs other than CIR circulating ICs are found whose nature is still unknown.

Antigen-Antibody Complex↗

[Immunopathological findings in herpes gestationis (author's transl)].

Herpes gestationis occurred in a 26-year-old woman during the last weeks of her second pregnancy. Within 8 days of the delivery the disease had progressed to such an extent that systemic treatment became necessary. Whereas pre-delivery treatment had consisted exclusively of local desinfection, and steroid and antibiotic ointments, treatment after delivery also included systemic use of prednisolone. After treatment for 3 weeks the skin changes had disappeared except for minimal pigmentation. Using immunofluorescent microscopy a complement activation in the dermo-epidermal junction and in adjacent clinically healthy skin could be demonstrated: There were massive linear depositions of C3, C1q and C4. In the basal membrane of the epidermis IgM could be demonstrated as an unusual finding. Further immunopathological features were found in the form of an immune complex vasculitis which could be shown during the active phase of the disease.

Adult↗

[Activation of the complement system in different forms of glomerulonephritis].

The complement system may be activated by two pathways, the classical and the alternate. To evaluate their respective participation in different forms of glomerulonephritis, the plasma values of C3, C4, C3PA, C1q and properdin were determined in 70 patients. In systemic lupus erythematosus (LED), acute poststreptococcal glomerulonephritis (AGN) and septicemia the classical pathway appears to be mainly involved, whereas the amplification loop and the alternate pathway seem to be of secondary importance. By contrast, in membranoproliferative glomerulonephritis (MPGN) the alternate pathway plays a major role. However, the present data suggest that activation of the classical pathway may often be involved as well. In minimal change glomerulonephritis no signs indicating involvement of the complement system were apparent. Follow-up observation demonstrated a correlation between decreases in plasma complement concentrations and the clinical severity of the primary disease in LED, AGN and septicemia, but not in MPGN.

Antigen-Antibody Complex↗

Inhibition of complement activation by IgG4 antibodies.

Prolonged exposure to antigens may result in high IgG4 antibody titres as was shown in a previous paper (Aalberse et al., 1983b). In novice bee keepers, a shift in the IgG1/IgG4 ratio of the response against phospholipase-A (PLA; a major component of bee venom) occurred. This resulted in an IgG4-dominated response after approximately 2 years of bee-keeping experience. Subject of the present study was the influence of relatively high concentrations of IgG4 antibodies on the biological activity of immune complexes. In the PLA antigen model, it was demonstrated that IgG4-containing immune complexes do not activate complement and that IgG4 antibodies effectively inhibit immune precipitation and complement activation by IgG1 antibodies. Evidence is provided that IgG4 antibodies inhibit binding of C1q to IgG1 in mixed, IgG1- and IgG4-containing complexes. It is proposed that IgG4 antibodies protect against the biological effects of the complement-fixing IgG subclasses. For this reason, determination of the total IgG response or just determination of antibody activity in the complement-fixing isotypes is insufficient in immune-complex diseases. The modulating effect of the non-complement-fixing isotypes should be taken into account to predict the biological activity of the immune complexes.

Antibodies, Monoclonal↗