Adverse clinical effects of immune sorption with staphylococcal protein A columns.

Abstract

S TAPHYLOCOCCAL Protein A (SPA) is a major constituent of the cell wall of certain strains of Staphylococcus aureus (eg, Cowan strain 1), which has a great affinity for mammalian immunoglobulin. Analogous immunoglobulin binding sites exist in some other bacteria3 SPA has five immunoglobulin binding regions at the N-terminus. Its one C-terminal nonimmunoglobulinbinding site serves to attach the protein to the cell wail. SPA binds avidly to the Fc portions of human immunoglobulin G (IgG) of types 1, 2, and 4, less reliably to type 3, weakly or variably to IgM, and IgA. 2-4 The binding is nonimmune. The affinity of SPA for IgG seems to be even greater (fivefold) when an antigen is bound to the IgG as an antigen-antibody complex. SPA is physically and chemically stable, and can be attached to various support matrices firmly enough to defy leaching, but without appreciable loss of its immunoglobulin-binding characteristic. Thus, it is possible to develop systems in which SPA, attached to an inert matrix in a column, can extract IgG and immune complexes from serum or plasma. In theory, it seems simple. In fact, the mechanism of action of SPA is complex, involving much more than removal of IgG and immune complexes. That is not the topic of this review, although it has a bearing on the types of reactions encountered. Suffice it to say that SPA affects the immune system in a variety of ways, activating complement, apparently by the alternative pathway, ~ reducing circulating immune complexes, possibly altering antigen-antibody ratios, and other forms of immune modulation. 5 In some clinical applications, such as with a fixed amount of plasma passing once through the sorbent, there seems to be little or no relationship between the quantity of plasma treated or of SPA used, 6 and the observed