The therapeutic uses of intravenous immunoglobulins in autoimmune rheumatic diseases.

Immunoglobulins (antibodies) are plasma proteins produced by B cells, which are essential in the defence against bacterial and viral infections. Dysregulation of the immune system can lead to the formation of autoantibodies and subsequent autoimmune disease. Therapy with immunoglobulin was first studied in the late 19th century, when Von Behring and Kitasato showed that serum taken from rabbits immune to tetanus toxins could protect non-immune rabbits from infection w1x. However, it was not until the 1960s that the first immunoglobulin preparations suitable for intravenous administration were formulated w2x. Subsequently, intravenous immunoglobulin (IVIG) was introduced as replacement therapy in patients with primary immunodeficiencies w3x. In the early 1980s, Imbach and collegues w4x were the first group to use IVIG in autoimmune disease. They gave patients with autoimmune thrombocytopenic purpura, who had been refractory to all conventional measures, an IVIG preparation as an experimental treatment. Their idea was that IVIG might interfere with the immune responses of the platelet-targeted autoantibody. Dramatic increases in platelet count were seen w4, 5x. Subsequently, the potential for using IVIG in autoimmune disease led to trials of its use in a wide variety of disorders (Table 1). There are large numbers of case reports and uncontrolled studies but few randomized controlled trials. This review provides a brief overview of the potential mechanisms of action and possible side-effects of immunoglobulin prior to highlighting the evidence for its use in autoimmune rheumatic diseases.