Immune complexes involve the binding of antigen to specific antibody and form part of the normal host response to foreign antigens. In some cases, immune complexes apparently can be deposited in tissues or organs and produce tissue injury. Blood vessels are most frequently involved. Although immune complexes may involve IgG, IgA, or IgM antibody, immunoglobulin G is the most common type. Immune complexes bind C1q and C3 components of complement. Cryoglobulins are immune complexes consisting either of monoclonal immunoglobulin complexes or, much more commonly, rheumatoid factor complexed with immunoglobulins (“mixed cryoglobulins”). Immune-complexes may be fixed to tissue, circulating in the blood, or both. Diseases associated with circulating immune complexes include certain parasitic (schistosomiasis), protozoal (malaria), viral (hepatitis virus and cytomegalovirus), and bacterial (SBE and meningococcemia) infections; various malignancies; and various inflammatory diseases with an autoimmune component such as the rheumatoid-collagen diseases and the vasculitides. However, circulating immune complexes have been detected in some way by some investigators in a great number of diseases.

Immune complexes can be detected in various ways. Immunofluorescent stains can be applied to tissue sections and visually demonstrate immunoglobulin binding to specific tissue locations. Circulating immune complexes (CICs) can be detected and assayed. The two most common methods include assays that detect C1q binding and methods that detect C3 activation such as the Raji cell assay. The C1q methods detect only CIC that activate complement by the classic pathway. The Raji cell assay uses tissue cultured cells derived from Burkitt’s lymphoma that have high-affinity binding capability for the C3b component of complement. This detects complement activation by either the classic or the alternate pathways. Currently, the Raji cell assay method seems to be used most frequently. An EIA method has also become available. Unfortunately, assay of CIC has not achieved clinical usefulness in any way comparable to their immunologic and basic science interest. Most diseases associated with CIC average at least 10% or more false negative results with current assay methods, so that a negative result does not exclude the disease or presence of the complexes. The frequent presence of detectable CIC in many conditions hinders interpretation of a positive result. Also, use of CIC levels as a parameter of therapeutic response has yielded contradictory and inconstant results in the literature. CIC assay seems to have been most useful in diagnosis and therapy of SBE, especially when related to prosthetic valves. In a patient with a prosthetic valve, absence of detectable CICs is some evidence against SBE. Serial measurement of CICs in SBE apparently has been more helpful in assessing effectiveness of therapy than in most other diseases.