Advances in our understanding of the pathogenesis of
rheumatic diseases such as
rheumatoid arthritis and
systemic lupus erythematosus have led to the emergence of
immunoglobulin-based
therapy as a major therapeutic force. Numerous
monoclonal antibodies that target proinflammatory
cytokines or their receptors (e.g.
infliximab,
adalimumab,
tocilizumab,
belimumab, HuMax-IL-15), and cell-surface or co-stimulatory molecules (e.g.
rituximab) are either in clinical development or have been approved for clinical use. These
antibodies are safe and effective in the long-term
therapy of many
rheumatic diseases. In addition, polyclonal
immunoglobulins (intravenous immunoglobulin) obtained from pooled plasma from healthy blood donors are an effective therapeutic approach in certain
rheumatic diseases. The mechanisms of action of
monoclonal antibodies and
intravenous immunoglobulin include cytolysis of target cells through
complement or antibody-dependent cell-mediated cytotoxicity, induction of apoptosis of target cells, blockade of co-stimulatory molecules, and neutralization of pathogenic
antibodies and soluble factors such as
cytokines and their receptors, which ultimately lead to amelioration of the inflammatory process. The success of currently available therapeutic
immunoglobulins has led to considerable interest in the identification of novel molecular therapeutic targets in
rheumatic diseases.