HOST FACTORS THAT INFLUENCE THE DEVELOPMENT OF IMMUNE COMPLEX DISEASE
The development of immune complex disease in experimental animals is clearly dependent on host factors. If several rabbits of the same strain, age, weight, and sex are immunized with identical amounts of a heterologous protein by the same route, only a fraction of the immunized animals will form antibodies, and of those, only some will develop immune complex disease. The magnitude of the response primarily depends on genetic factors. The extent of tissue involvement is likely to depend on the general characteristics of the anti-bodies produced (such as affinity, complement-binding ability, capacity to interact with cell receptors) as well as on the functional state of the RES of the animal.
The affinity and number of available Fcγ receptors on professional phagocytic cells (PMN leukocytes, monocytes, and macrophages) are important in the expression of IC dis-ease. If IC are predominantly taken up by those cells in tissues where they abound, such as the liver and spleen, the likelihood of developing tissue inflammation is limited. Support for the importance of Fc-mediated clearance of IC as a protective mechanism was obtained in experiments in which the Fc receptors were blocked. This resulted in decreased IC clear-ance and increased pathogenicity.
Patients with systemic lupus erythematosus and rheumatoid arthritis have decreased ability to clear antibody-sensitized red cells, indicating a general inability to clear circulating IC. Some patients with lupus nephritis have a distinct FcγRII allele expression. It is speculated that the abnormal allele is functionally deficient and that the lack of clearance of IC may then favor glomerular deposition.
The ability to interact with complement receptors may also be an important determi-nant of pathogenicity. C1q, C3b, C3c, and C3d are readily detected in IC. This may allow IC to bind to cells expressing the corresponding complement receptors. As mentioned above, binding of IC to CR1 expressed on the surface membrane of red cells facilitates their clearance for the circulation . In patients with SLE and other IC diseases, the number of CR1 on the surface of red cells is decreased and this may contribute to decreased IC clearance. This decreased CR1 expression has been claimed to be genetically deter-mined in SLE. However, it is possible that the decrease may not be numerical, but func- tional. In other words, in patients with high concentrations of circulating IC CR1 may be saturated and this may result in blocking of the receptors by IC causing a decrease in the number of available receptors.
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