Last updated: October 9, 2014
Description: Immune complexes composed of antibody and antigen are responsible for pathophysiologic findings in various autoimmune and infectious diseases. The ability of immune complexes to cause injury depends on their deposition in some tissues and subsequent activation of the complement system, phagocytic leukocytes, and other inflammatory mediators.
Deposition of immune complexes in specific tissues depends on a number of factors related to the immune complex itself as well as local factors. For example, the size of immune complexes is critical. Very small immune complexes (typically seen early in an immune response, in states of antigen excess) are readily eliminated and seldom cause tissue injury. Very large immune complexes (usually seen late in the immune response, in states of antibody excess) are efficiently removed by phagocytic cells of the reticuloendothelial system and seldom cause tissue injury. Immune complexes that are prone to deposit and cause injury are often those formed when circulating antigen and antibody are present in roughly equal amounts. Thus, in a immune reaction to a foreign protein, the clinical picture of immune complex deposition may be seen transiently as the immune response switches from a state of antigen excess to one of antibody excess. Other factors that affect tissue deposition of immune complexes include the electric charge of the complex, local blood pressure, and flow patterns (e.g., turbulence).
Methods: Circulating immune complexes may be detected by several methods. Physical methods, such as precipitation with high molecular weight polymers, such as polyethylene glycol, take advantage of the large size of immune complexes and allow direct quantification of the protein concentration in the complex. Other physical methods include gel filtration, cryoprecipitation, and nephelometry. Immune complexes activate the complement cascade via interaction with the C1q component of complement. Thus, C1q can be used in various assays such as a solid-phase radioassay to estimate the concentration of immune complexes in samples. As they activate the complement cascade, complement fragments such as C3d become bound to immune complexes. Assays such as the Raji cell assay take advantage of this by quantifying the amount of immune complex that binds to cell surface complement receptors. Samples should be sent to the laboratory immediately or refrigerated because complement and immune complexes deteriorate at room temperature.
Normal Value: Immune complexes are normally not present or not detected.
Clinical Associations: Clinical expression of immune complex disease varies with the tissues involved. For example, deposition of immune complexes in the kidney (e.g., in bacterial endocarditis) causes glomerulonephritis. Serum sickness, a constellation of symptoms that includes arthralgias, arthritis, lymph-adenopathy, fever, and urticarial, petechial, or macular skin lesions, results from widespread deposition of immune complexes in various organs.
Immune complex formation and deposition play a part in a number of diseases. The relevant antigens include exogenous antigens (e.g., drugs, foreign proteins, vaccines); infectious agents (e.g., bacteria such as staphylococci, streptococci, mycoplasma, treponemes; parasites such as plasmodia, Toxoplasma, Schistosoma; viruses such as hepatitis B, Epstein-Barr, cytomegalovirus); endogenous or self-antigens (as in SLE, RA, cryoglobulinemia, tumor antigens). In some cases, specific antigens may be typically associated with particular end-organ manifestations, such as arthritis associated with hepatitis B or the glomerulonephritis associated with staphylococcal endocarditis. In other cases, many antigens may produce a similar constellation of symptoms, such as serum sickness related to various endogenous or infectious agents.
Cost: Raji, $140–165; C1q, $95–130.
Comment: Immune complex assays are seldom used in clinical practice because they are expensive, etiologically nonspecific, poorly correlated with each other, and slow because many are performed primarily in reference laboratories. Some investigators and researchers still use these assays as sequential indicators of disease activity in diseases characterized by immune complex formation (e.g., SLE) or to aid in the diagnosis of patients with multisystem disease. Because circulating immune complexes are very efficient at activating the complement system, some investigators use direct measurements of complement proteins or their split products to provide indirect evidence of immune complex involvement in disease processes.