Measurement of immune complexes is not useful in routine clinical practice

Abstract

The vogue for the determination of immune complexes (ICs) in the clinical setting has now passed, as can be seen from the fact that only two of the regional immunology reference laboratories in the UK still offer a service. This is partly due to the lack of speci®city seen in the assays available, which, apart from minor modi®cations, have remained essentially unchanged. They have not lived up to their initial promise and are unlikely to be offered by service laboratories in the future. In this review we consider when these assays may still have a role and which might be the most useful in a particular clinical setting.An IC is formed when an antibody reacts speci®cally with its corresponding antigen. The size of the complex formed is dependent on many factors, including the ratio of antibody to antigen, the valency of the antigen and the avidity of the antibody±antigen reaction. IC formation is an integral part of the normal immune response to infection and usually takes place without adverse pathological consequences. ICs are captured by speci®c receptors, in particular on erythrocytes, and transported to the reticuloendothelial system for processing and removal. The events leading to IC formation and subsequent removal are summarized in Fig. 1. There are, however, various disorders in which ICs play an important role in the disease process. These include some forms of vasculitis (e.g. Henoch±SchoÈ nlein purpura), infectious disorders (e.g. bacterial endocarditis, shunt nephritis) and connective tissue autoimmune disorders [e.g. rheumatoid arthritis (RA), systemic lupus erythematosus (SLE)]. The pathology generally arises from inappropriate clearance or deposition of ICs. Thus, vasculitis DETECTION OF CIC IN BODY FLUIDS (USUALLY SERUM)At least 40 different assays for CICs have been described. They vary widely in terms of disease sensitivity, speci®city and clinical applicability. Possibly the major area of investigation has been in autoimmune disease, in particular SLE. SLE has been considered the archetypal IC disease. Many of the disease manifestations, including

Neutrophil FcγRIIA availability is associated with disease activity in systemic lupus erythematosus

“…Further, ICs are engulfed by immune cells causing inflammation including induction of type I interferons (IFNs) [1,2], as well as the formation of neutrophil extracellular traps (NETs) [3,4]. Although central to the disease pathogenesis, levels of circulating ICs are rarely measured in reference laboratories due to the lack of specificity in current assays with a broad array of assay measuring different features of ICs [5]. Early studies detected circulating ICs by their capacity to bind to neutrophils as determined by immunofluorescence techniques [6][7][8].…”

Electrophoretic and immunoelectrophoretic characteristics of IgG as a constituents of peg precipitable immune complexes in preruminant calves' sera

“…These IgG molecules belong to electrophoretically faster IgG molecules of IgG1 subclass. It is known that PEG, beside immune-complexed immunoglobulins, also precipitates other serum proteins (Monay et al, 1983;Robinson et al, 1989) and therefore the PEG assay is considered as a nonspecific screening test for the presence of immune complexes (Lock and Unsworth, 2000;Nash and Davis, 2000). These selective precipitations of some molecular forms of IgG1 molecules were noticed in 6-hour to one-month old calves.…”

“…These non-immunoglobulin proteins can be the real element of IC or be co-precipitated by non-specific protein aggregation (Nash and Davis, 2000). Also, PEG precipitates could contain monomeric IgG in small amounts (Lock and Unsworth, 2000). This fact pointed the necessity for more detailed analyses of immunoglobulins and other constituents of IC in healthy calves.…”

“…It represents a widely used method for routine determination of circulating IC level (Lock and Unsworth, 2000) that allows both, the quantification of circulating IC, and the analyses of the composition of PEG precipitable material. It represents a widely used method for routine determination of circulating IC level (Lock and Unsworth, 2000) that allows both, the quantification of circulating IC, and the analyses of the composition of PEG precipitable material.…”

New ELISA Kits using C3 Binding Glycoprotein from Cuscuta europea Detect Mainly IgM CIC in Rheumatoid Arthritis and Progressive Systemic Sclerosis, but not in Systemic Lupus Erythematosus

“…At present ANTI-C3 ELISA and the conglutinin test are the most used antigen-nonspecific assays able to detect CIC according to the immunoglobulin isotypes contained (IgG-CIC, IgM-CIC and IgA-CIC) (Iida et al, 1987;Ruddy and Moxley, 1994;Lock and Unsworth, 2000). Unfortunately, both tests can detect false positive results (Aguado et al, 1985;Holmskov et al, 1992).…”