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[Current overview of diagnostic possibilities of complement analysis].

The complement system is composed of at least 21 serum proteins and 8 cell surface receptors sensitive to complement components or their fragments. Qualitative and quantitative analysis of complement components in clinical samples has become standard procedure in many laboratories thanks to the availability of easy-to-perform test kits. However, interpretation of results is still a task that requires great skill and the situation are rare, in which analysis of the complement system goes beyond diagnosis into therapeutic consequences. The present paper is an update of previous similar reviews now available in the international literature; in addition, the author attempts at bringing the often complicated world of complement and clinical practice together and thus contributes to answering the question: what should the clinician know about complement?

Antigen-Antibody Complex↗

Assays for complement activation.

Complement is a major biologic mediation system that functions in host defense against microorganisms and other pathogens and also aids in the elimination of damaged and abnormal cells. This is accomplished by its ability to mediate the destruction of pathogens and altered cells directly through cytolytic and cytotoxic properties, as well as indirectly by its ability to augment the actions of various effector cells, which in turn destroy or inactivate these substances. Its second major action in vivo is the production of an acute inflammatory response that, by altering blood-vessel permeability, contracting smooth muscles, and promoting an influx of leukocytes, aids in the localization of the injurious process responsible for complement activation and retards its spread and dissemination throughout the body. The actions of the activated complement system upon pathogens and altered cells, as well as its phlogistic properties, are the direct consequence of the actions of complement protein-protein complexes, enzymes, peptides, and cleavage products on the activator, on biologic membranes, and on various effector and other tissue cells. Complement activation is a frequent phenomenon in infectious diseases, autoimmune diseases, and many other conditions having an inflammatory component. Because of the importance of this system in contributing to the resolution of the disease process, monitoring of the status of the system in patients is frequently indicated. Monitoring of the complement status is also appropriate in numerous other diseases, such as those with an inflammatory component, in which complement activation occurs secondarily but in which it is frequently responsible for confining the injurious process and aiding in its resolution. A number of techniques are available to assess the status of the complement system in samples obtained from patients. Among these are a group of newer tests that specifically detect complement activation. They quantitate activation-dependent complement cleavage products, antigenic changes, or protein-protein complexes. These tests are quantitative, highly sensitive, and extremely specific; furthermore, most can be employed with samples obtained from patients. Because all of the biologic actions of the complement system require complement activation, such newer activation-specific assays permit the precise evaluation of the status of this system in human diseases. Further extension of their use to additional patients and other disease complexes will undoubtedly increase the understanding of the biologic importance of the complement system in human disease processes.

Complement Activation↗

Complement research.

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Allergy and Immunology↗

[Elimination of immune complexes: role of complement].

For many years it has been considered that complement does not modify the immune elimination of antigen-antibody complexes. However, recent studies suggest that complement contributes to the normal processing of immune complexes: (1) complement activation modifies the structure of the immune complex lattice and produces soluble complexes, (2) erythrocytes bind complement reacted complexes and deliver them to the fixed macrophage system. The clinical association between inherited complement deficiency and immune complex mediated diseases also suggests a role for complement in the physiological elimination of complexes.

Antigen-Antibody Complex↗

Complement activation in sickle cell disease: a liposome model.

Patients with sickle cell disease (SCD) have poorly defined abnormalities of their alternative complement pathway (ACP). We have previously shown chronic activation of the ACP in these patients. To determine the mechanism of this finding, we studied concentrations of the complement control proteins factors I and H in serum from patients with SCD and found no significant difference when they were compared with a control population. Because certain membrane surfaces promote ACP activation and changes occur in erythrocyte membrane phospholipid organization with sickling, we used a liposome model to determine whether ACP activation could be caused by abnormal phospholipid organization of sickle cells. Liposomes with the composition of the sickle cell outer leaflet, which is enriched in phosphatidylserine and phosphatidylethanolamine, activated the ACP significantly more than liposomes with normal outer leaflet phospholipid content. Similarly, liposomes with the composition of the erythrocyte inner membrane leaflet, containing large amounts of phosphatidylethanolamine and phosphatidylserine, activated the ACP more than liposomes with the phospholipid content of the outer leaflet. These findings suggest that phospholipid composition of membranes may play a role in their ability to promote ACP activation, and that changes in phospholipid organization in sickle cells may contribute to the chronic ACP activation observed in patients with SCD.

Anemia, Sickle Cell↗