Pathomechanisms of Dextran-Induced Anaphylactoid/Anaphylactic Reactions in Man

Abstract

Immune complex-mediated (type III) anaphylaxis is shown to be the pathomechanism of severe dextran-induced anaphylactic reactions in man. Mild reactions may be either antibody-dependent or not. Patients with severe reactions have regularly high titers of preformed, circulating dextran-reactive antibodies and represent a small subpopulation of high responders to dextran. Upon infusion of clinical dextran, noxious immune complexes are formed, leading to mediator release and symptoms of anaphylaxis. Consequently, application of the hapten inhibition principle is recommended for prevention of such reactions.

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

“…ICs are known to mediate type 3 HSRs in a small subset of people receiving dextran infusions. In these cases, ICs are formed and mediate severe reactions in patients with high antidextran IgG antibody levels (Bircher, Hedin, and Berglund 1995;Hedin et al 1980;Hedin and Richter 1982;Kraft et al 1982;Ljungstrom et al 1983Ljungstrom et al , 1988.…”

Dextran-Reactive Antibodies in Healthy Infants and Toddlers – Relation to Type of Feeding

“…Naturally occurring dextran-reactive antibodies (DRA) are frequently present in sera from normal hu mans who have never received infusions of clinical dextran [1], Reasons for the presence of DRA in nor mal humans are not fully understood although there are several possible explanations. The antigen may be dextran itself originating from food [2], or dextran-producing bacteria in the gastrointestinal tract [3].…”

“…pneumococci, Salmonella typhi and streptococci [4], Recently an ubiquitous antigen occurring in low levels in tissues and sera of humans could be identified as native dextran [5], DRA can be demonstrated in the majority of heal thy adults. High titers of 512 and more, which rarely may be associated with anaphylactoid reactions after intravenous infusion of clinical dextran, have been demonstrated in 4% of random population samples [1], Less is known about the presence of DRA in chil dren. The time of appearance of such antibodies in healthy humans could possibly provide some further information concerning the origin of DRA.…”

Comparison of the Anaphylactoid Response Induced in Rats by Castanospermine and Dextran

“…The release of these amines causes cutaneous vasodilation, resulting in erythema, and in creased vascular permeability, resulting in edema. The remarkable tissue distribution of the reaction is not understood, but it does correlate with the num bers of mast cells in different areas of skin [20,21], The mechanism by which dextran elicits mediator re lease from rat mast cells in certain tissues is unknown, but in man it has been established that the occurrence of severe reactions correlates with the presence of IgG antibodies to dextran [22], No such antibodies have been found in rats. A minimum molecular weight range (10 kilodaltons) is necessary for elicitation of the response in rats [23,24] and certain monosaccha rides (glucose, mannose, xylose, galactose) can block the response [25,26], It has therefore been suggested that dextran binds to a lectin-like receptor of appro priate specificity present in the membranes of certain rat mast cells and thereby triggers mediator release [11,25,26],…”

“…The species and strain specificity is such that it is not possible to predict whether it may occur in man. However, dex tran has found considerable clinical usage as a plasma volume expander despite the occurrence of occa sional anaphylactic reactions [22]. Therefore, it seems unlikely that this property of castanospermine or its analogues would preclude clinical use in man.…”