The Significance of Complement in Immunohematology

Abstract

In vitro detection of red cell-bound complement can be important in the differential diagnosis of autoimmune and drug-induced immune hemolytic anemias; it can also be a sensitive test for the detection of complement-binding alloantibodies, e.g., in compatibility testing. Red cell-bound complement can be detected by the antiglobulin test if suitable antiglobulin sera (AGS) are utilized. In 1971, the Federal Standards for AGS were criticized because so-called broad spectrum AGS used routinely in blood banks were shown to often be deficient in anticomplement reactivity. In the new few years commercial regents changed with regard to the quantity and specificity of their anticomplement components. A great deal of controversy developed as to the true importance of detecting red cell-bound complement, the particular fragments of complement that should be detected, and the causes of nonspecific reactions that seemed to be occurring, especially with the increasing usage of new techniques utilizing low ionic strength media. When monospecific anti-IgG and anti-C3 became available commercially, the controversy regarding diagnostic testing was resolved as direct antiglobulin testing could be performed with these reagents rather than the broad spectrum reagents. Two main questions remained: how rare are alloantibodies that are only detectable by the anticomplement component of AGS? How clinically significant are such antibodies? The results of our 3-year study indicated that such antibodies (usually anti-Kidd) occurred with a incidence of 1/8000 sera tested. Some of these antibodies seemed capable of shortening the life span of transfused red cells, as determined by 51Cr survival studies; some showed negligible cell destruction. Severe transfusion reactions due to such antibodies would seem unlikely. Individual laboratories will have to balance the risk of missing some complement-dependent antibodies of possible clinical significance with the increased nonspecificity encountered in their own laboratory with AGS containing anticomplement.

Effect of Cell-Bound Proteins on the in vivo Survival of Circulating Blood Cells

“…As mentioned earlier, complement is de tected relatively commonly on the RBCs of patients [27,28]; this is usually not associ ated with the presence of hemolytic anemia. Chaplin et al [16] used a sensitive radiola beled antiglobulin method to quantitate RBC-bound C3d of normal subjects and ran dom hospitalized patients.…”

“…suggest that the more sensitive assay described by Kay [36] [24,25]. There are many more reasons why RBCs may have complement on their mem brane than why IgG should be present [27,28]; some of these were discussed earlier.…”

“…There are many reasons why RBCs may have small amounts of complement on their surface, other than as a result of complement activation by RBC auto-and alloantibodies [27,28]. One reason is that RBCs have a complement receptor (CR1) present on their membrane.…”

Analytic Reviews : Hemolytic Transfusion Reactions: A Review of Mechanisms, Sequelae, and Management

“…The role of complement in the pathogenesis of hemolytic transfusion reactions is critical [8]. Complement may become activated when the C1 recognition unit, which has five combining sites, contacts an antibody-bearing red cell.…”

Pathogenetische Bedeutung von Autoantikörpern

“…So verursachen beispielsweise verschiedene antierythrozytäre Antikörper eine komplementabhängige Hämolyse [11], Autoantikörper gegen Faktor-VIII oder andere Gerinnungsfaktoren hemmen in vitro die Gerinnung [23], neutrophile Granulozyten werden durch Antineutrophilen-Antikörper (ANCA) unter bestimmten In-vitro-Bedingungen aktiviert und degranuliert [41], Antikörper gegen das 180kD-Antigen von Patienten mit bullösem Pemphigoid stören die Bildung von Hemidesmosomen in vitro [25] und UV-Licht behandelte kultivierte Keratinozyten von Patienten mit neonatalem Lupus-Syndrom werden durch SS-A-und SS-B-Antikörper in Gegenwart von Komplement geschädigt [55]. So verursachen beispielsweise verschiedene antierythrozytäre Antikörper eine komplementabhängige Hämolyse [11], Autoantikörper gegen Faktor-VIII oder andere Gerinnungsfaktoren hemmen in vitro die Gerinnung [23], neutrophile Granulozyten werden durch Antineutrophilen-Antikörper (ANCA) unter bestimmten In-vitro-Bedingungen aktiviert und degranuliert [41], Antikörper gegen das 180kD-Antigen von Patienten mit bullösem Pemphigoid stören die Bildung von Hemidesmosomen in vitro [25] und UV-Licht behandelte kultivierte Keratinozyten von Patienten mit neonatalem Lupus-Syndrom werden durch SS-A-und SS-B-Antikörper in Gegenwart von Komplement geschädigt [55].…”