Protein A immunoadsorption - Clinical potential

Protein A is a staphylococcal bacterial cell wall component that binds certain subclasses of IgG, other classes of mammalian immunoglobulins and immune complexes. Initial studies in tumour-bearing animals and in patients with cancer were based on the early premise that circulating immune complexes function as suppressor factors of anticancer immunity. Subsequently, the use of protein A in various autoimmune disorders was explored. All these early studies utilised protein A-bearing staphylococci as an extracorporeal immunoadsorbent to remove IgG and immune complexes. Although promising clinical responses in cancer and various autoimmune illnesses were observed, there was also substantial toxicity. We now understand this toxicity to be due to leakage of protein A and enterotoxins from the formalin-fixed Staphylococcus aureus. As a result, more stable protein A matrices were developed. The 2 leading extracorporeal protein A devices, the Immunosorba(R) and Prosorba(R) columns, utilise highly purified protein A covalently coupled to a relatively inert solid phase matrix. Although these devices differ in design and utilisation, both have demonstrated clinical effectiveness in several autoimmune illnesses, with manageable adverse effects. The Immunosorba(R) column has been licensed in the US for the treatment of immune-mediated haemophilia, and the Prosorba(R) column is approved for the treatment of idiopathic thrombocytopenic purpura. Use of the Prosorbao(R) column in various other autoimmune disorders. including rheumatoid arthritis and renal graft rejection, is under investigation. There is also some evidence that certain canters may respond to immunoadsorption therapy, provided that concomitant chemotherapy is used. In addition to its reported clinical benefit, protein A immunoadsorption may provide further insights into the clinical pathogenesis of immune-mediated disorders and certain cancers. Analysis of the composition of immune complexes from patients during therapy, including the nature of bound antigen, may substantially further our understanding of the role of these immune complexes in these disorders. Indeed, different modes of action may be operative depending upon the type of illness.