Interpretation of Serological Complement Biomarkers in Disease

Abstract

Complement system aberrations have been identified as pathophysiological mechanisms in a number of diseases and pathological conditions either directly or indirectly. Examples of such conditions include infections, inflammation, autoimmune disease, as well as allogeneic and xenogenic transplantation. Both prospective and retrospective studies have demonstrated significant complement-related differences between patient groups and controls. However, due to the low degree of specificity and sensitivity of some of the assays used, it is not always possible to make predictions regarding the complement status of individual patients. Today, there are three main indications for determination of a patient's complement status: (1) complement deficiencies (acquired or inherited); (2) disorders with aberrant complement activation; and (3) C1 inhibitor deficiencies (acquired or inherited). An additional indication is to monitor patients on complement-regulating drugs, an indication which may be expected to increase in the near future since there is now a number of such drugs either under development, already in clinical trials or in clinical use. Available techniques to study complement include quantification of: (1) individual components; (2) activation products, (3) function, and (4) autoantibodies to complement proteins. In this review, we summarize the appropriate indications, techniques, and interpretations of basic serological complement analyses, exemplified by a number of clinical disorders.

Das Komplementsystem: von den Grundlagen zur klinischen Bedeutung

“…B. C1-INH, C1q, Faktor H und die C3-Konvertase des Alternativwegs umfassen. Diese Autoantikörper haben sich als diagnostische oder prognostische Marker sowie zur Therapieüberwachung bewährt [149,150]. Der Nachweis dieser Antikörper erfolgt zumeist mittels ELISA, wobei das entsprechende Autoantigen auf Mikrotiterplatten immobilisiert wird.…”

Discrepancies in plasma levels of complement components measured by a newly introduced commercially available magnetic bead technique compared to presently available clinical reference intervals

“…A novel indication is to monitor patients on complement regulatory drugs. This indication may be expected to increase in the near future because there are many such drugs, under development or in clinical trials in addition to the limited number which are already used in the clinic …”

Complement activation in individuals with previous subclinical Lyme borreliosis and patients with previous Lyme neuroborreliosis

“…The complement system is a part of the innate immunity and provides a link to the adaptive immune system. It consists of a large number of plasma and membrane-linked proteins that work in a close network and a cascade-linked manner [14][15][16].…”

“…The complement system may be activated through three pathways depending on the recognition molecule. The classical pathway is activated when C1q binds to antigen bound IgM or IgG, the lectin pathway is activated when mannan-binding lectin (MBL), collectins or ficolins bind to carbohydrates on the pathogen surface and the alternative pathway is activated when C3b or C3(H 2 O) binds to the pathogen surface [14]. Activation of the complement system leads to cleavage of C3 into C3a and C3b by C3 convertase followed by cleavage of C5 into C5a and C5b which initiate the formation of the terminal complement complex C5b-9 (sC5b-9 in soluble form in plasma and membrane attack complex, MAC when inserted in cell membrane).…”