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[Quantitation of intact form of complement protein B and its fragment Ba in human serum by radioimmunoassay].

A sensitive solid-phase radioimmunoassay for intact complement protein B and its smaller fragment Ba is described which quantitates human B and Ba to 30 ng/ml. The assay was proved to be useful to evaluate the activation of the alternative pathway of the complement system by measuring intact B and Ba in normal human sera activated with zymosan. In sera from patients with systemic lupus erythematosus (SLE), the level of intact B was decreased and that of Ba was increased in the active phase, and the level of Ba was increased though intact B which was within normal limits in the inactive phase. The present result suggests that the activation of the alternative pathway is occurring both in the active and inactive phase in SLE, and the measurement of intact B and Ba concentration in pathological sera would be useful to evaluate the activation of the alternative complement pathway.

Adult

A comparison of immunologic profiles and their influence on bacteremia in surgical patients with a high risk of infection.

Prospective sequential studies of the antibacterial function of neutrophils, lymphocyte responsiveness, opsonic capacity of serum and serum levels of C3(B), properdin, factor B, IgG, and albumin were made in 32 patients with severe burn injury (greater than or equal to 45%), 21 patients with severe multisystem traumatic injury, 20 high-risk, infected patients, and 22 renal transplant patients. Fifty-five episodes of bacteremia occurred in 37 of the 95 patients. Abnormal neutrophil function was clearly associated as a predisposing factor to these episodes, whereas there was no association between bacteremia and low serum levels of C3, IgG, factor B, or properdin. C3, factor B, and IgG usually rose following bacteremia as acute phase proteins, but there was evidence of a consumptive opsoninopathy in 11% of episodes. Defective opsonization was associated with a high risk of bacteremia only when there was a coexisting abnormality of neutrophil function (88% of such patients became bacteremic). None of 27 nonburned patients tested with delayed hypersensitivity antigens responded normally, and there was regularly depression of lymphocyte responsiveness to phytohemagglutinin-A and concanavalin-A in a whole blood assay related to serum immunosuppressive factors, but poor responsiveness was not associated with bacteremia.

Adolescent

The biological role of the complement system and the clinical importance of complement measurements.

Properties of serum proteins belonging to the complement system, two pathways of the complement activation (classical and alternative pathway) as well as the physiological role of the complement system are discussed. Complement has essential importance in some physiological processes: In the induction of the humoral immune response, in the elimination of immune complexes and in the protection against bacterial and viral infections. After a short discussion of the genetics of the complement system, the principle and possibilities of clinical applications of the complement measurements are described. Finally, different approaches to the therapeutic manipulation of the complement system are discussed.

Angioedema

Restoration by purified C3b inactivator of complement-mediated function in vivo in a patient with C3b inactivator deficiency.

In a patient with lifelong increased susceptibility to infection and multiple abnormalities in complement-mediated functions, the infusion of normal plasma had been seen to produce a prolonged partial correction of serum abnormalities. It was subsequently shown that the patient was genetically deficient in the C3b inactivator and that immunochemical depletion of C3b inactivator from normal serum resulted in abnormalities similar to those found in the patient's serum, including alternative pathway C3 activation. Highly purified C3b inactivator was obtained from the euglobulin fraction of normal human serum, sterilized by filtration, and infused intravenously. Partial or complete correction of almost all the known serum abnormalities was obtained. C3b almost disappeared from the serum within 4-5 h, as did Factor C activity. Native C3, C5, and serum hemolytic activity rose to normal or near-normal levels over 4 days and were sustained for another week. Factor B, properdin, opsonic activity, and bactericidal activity reached a level at least two-five times that found before the infusion within 24 h and fell over the next 5 days. These observations prove the primary role of C3b inactivator deficiency in the patient's disease and demonstrate clearly the curcial role in vivo of C3b inactivator in modulating alternative pathway activity.

Blood Proteins

Complement receptor subtypes C3b and C3d in lymphatic tissue and follicular lymphoma.

To substantiate the origin of follicular (nodular) lymphoma cells from germinal-centre cells, the lymphoma cells from 7 patients with follicular lymphoma and from 9 tonsils and 2 lymph nodes were studied for the presence and distribution of complement-receptor subtypes (i.e., the receptors for C3b and C3d). It was found that erythrocytes coated with antibodies and C3d (EAC3d) adhered exclusively to germinal centres, whereas erythrocytes coated with antibodies and C3b (EAC3b) adhered to germinal centres and in many instances to the regions between them. These findings indicate that germinal-centre cells bear both complement-receptor subtypes and that the B cells of the interfollicular area, which belong at least in part to the precursors of plasma cells, bear only a receptor for C3b. In frozen sections of follicular lymphomas, a similar distribution of complement-receptor subtypes was observed; EAC3d was bound exclusively to the neoplastic nodules, and EAC3b adhered to the neoplastic nodules and adjacent paranodular tissue. Receptor studies on suspended cells of both normal tonsils and follicular lymphomas revealed a slight predominance of EAC3d(+) cells or equal numbers of EAC3b(+) and EAC3d(+) cells. The complete congruence in the expression and distribution of complement-receptor subtypes between tissues from follicular lymphomas and those from normal and hyperplastic tonsils or lymph nodes suggests that follicular lymphoma represents the neoplastic counterpart of the reactive germinal centre.

Binding Sites