THERAPEUTIC APPROACHES TO
IMMUNE COMPLEX DISEASE
The most common types of therapy in immune
complex disease are based on four main approaches:
1.
Eradication
of the source of persistent antigen production (e.g., infections, tu-mors).
2.
Turning
off the inflammatory reaction (using corticosteroids and nonsteroidal agents).
3.
Suppression
of antibody production using immunosuppressive drugs such as cy-clophosphamide,
azathioprine, or cyclosporine. This is the mainstay of IC dis-ease treatment,
particularly when autoimmune reactions are on its basis.
4.
Removal
of soluble IC from the circulation by plasmapheresis, a procedure that consists
of the removal of blood (up to 5 L each time), separation and reinfusion of red
cells, and replacement of the patient’s plasma by normal plasma or
plasma-replacing solutions. Plasmapheresis appears most beneficial when
asso-ciated with the administration of immunosuppressive drugs; by itself, it
can even induce severe clinical deterioration, perhaps related to changes in
the im-munoregulatory circuits. The main drawbacks of plasmapheresis are its
high cost (derived from the sophisticated equipment used and from the cost of
plasma and plasma-replacing products) and the fact that it can only be
adequately performed in a well-equipped medical center.
In the last few years there has been
considerable interest in applying emerging basic concepts on the pathogenesis of
inflammation on the treatment of a variety of conditions in which IC formation
or deposition may play an important role. Three major approaches have been
tried:
1.
Blocking
critical cytokines, such as TNF. This has been done either with mono-clonal
antibodies reacting with pro-inflammatory cytokines, with cytokine re-ceptor
antagonists, or with recombinant cytokine receptors. A soluble TNF-re-ceptor-Fc
fusion protein, which blocks the effects of TNF, has been approved by the FDA
for use in rheumatoid arthritis.
2.
Interruption
of the interaction between leukocyte integrins and endothelial cell adhesion
molecules. Humanized anti–CAM-1 (and other cell-cell interaction-fa-cilitating
molecules) as well as soluble forms of these molecules have been suc-cessfully
tested in animal models.
3.
Inhibition
of the complement activation cascade using soluble forms of regula-tory
proteins (C1 inhibitor, MCP, DAF, CR1) and antifactor antibodies (anti-C5
antibody) with the goal of inhibiting the production of C3a and C5a .
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