Anaphylactoid reactions to infusions of plasma protein and human serum albumin Role of aggregated proteins and of stabilizers added during production

Abstract

Summary Six patients suffering from anaphylactoid reactions after infusion of pasteurized plasma (PP) or human serum albumin (HSA) were investigated. Clinical symptoms ranged from urticaria and hypotension to cardiac arrest. Immunoglobulin levels, especially of IgA, were normal, as were concentrations of complement factors C3, C4 and factor B. In skin and lymphocyte transformation tests patients, with the exception of one severely allergic to protein, did not react to the monomeric pure HSA. Five out of six patients reacted against HSA aggregates and three patients to the HSA modified by caprylate added as stabilizer during commercial HSA production. It is concluded that the anaphylactoid reactions developing after PP or HSA infusion result from a non‐specific reaction to protein aggregates and in some cases possibly from a specific immune response to the caprylate‐modified HSA.

Stability of monoclonal antibodies (mAbs)

“…Aggregates have also been implicated in a heightened immune response (Moore & Leppert, 1980;Ratner, Phillips, & Steiner, 1990;Ring, Stephan, & Brendel, 1979;Underwood, Voina, & Van Wyk, 1974), and adverse events due to antibody aggregates have also been reported (Demeule, Gurny, & Arvinte, 2006;Ryan, Webster, & Statler, 1996). The concern over mAb aggregates especially for IV dosing has resulted in a limitation by the World Health Organization (WHO) of less than 5% aggregate in commercialized mAb therapeutics.…”

Febrile and Allergic Reactions after Transfusion of Platelet Concentrates

“…It has been reported that allergic reactions can also be triggered by passively transfused specific IgE from the donor [24], but the relevance of this finding is unclear. Also nonspecific reactions to plasma proteins of the donor might explain some of the anaphylactoid reactions as it is known for infusion of human serum albumin preparations [25]. However, little is known about the impact of this phenomenon in the context of PC transfusion.…”

Engineering Aggregation Resistance in IgG by Two Independent Mechanisms: Lessons from Comparison of Pichia pastoris and Mammalian Cell Expression

“…[9][10][11][12][13][14] Aggregation of even only a few percent of the administered therapeutic antibody can cause severe problems, as already low amounts of aggregates have long been known to cause anaphylactoid reactions. 15,16 Therefore, engineering IgG to reduce or eliminate its selfassociation is of great importance and might further extend the potential of therapeutic antibodies.…”