Antibodies to polyethylene glycol (PEG) were raised in rabbits by immunization with monomethoxy polyethylene glycol modified ovalbumin (OA), bovine superoxide dismutase (SOD), and ragweed pollen extract (Rag), given in Freund’s complete adjuvant (FCA). Immunogenicity depended on the nature of the protein and the degree of modification. With modified OA, in the presence of FCA, the majority of animals showed an anti-PEG response. With modified SOD and Rag only a small proportion of animals responded. In the absence of FCA, modified OA, given s.c, did not elicit any anti-PEG antibody response in rabbits and only a weak response in mice. PEG of Mw 10,000 and 100,000 given in FCA was found nonimmunogenic in rabbits, and PEG of Mw 5.9 × 10⁶, given s.c. to mice, showed no or very poor immunogenic properties. Gel diffusion, heterologous passive anaphylaxis and passive hemagglutination were used to demonstrate anti-PEG antibodies raised to PEG-modified proteins. Specificity was confirmed by hapten inhibition of precipitation, inhibition of passive hemagglutination and cross-reactivity tests. PEG of Mw ≥ 4,000 produced specific precipitates, smaller molecules acted as monovalent haptens. From hapten inhibition of precipitation by PEG of Mw 300 it appears that the antigenic determinant of PEG may be a sequence of 6–7 -CH₂CH₂O-units. Anti-PEG antibodies can be used analytically. By gel diffusion, Peg was detected in minimal concentrations of 0.1–1 μg/ml. The clinical relevance of these findings with regard to therapy with PEG-modified enzymes and allergens in humans remains to be established.

Antibodies to polyethylene glycol (PEG) were analyzed in patients with various allergies and in healthy blood donors employing passive hemagglutination. In untreated allergic patients and in healthy blood donors, naturally occurring anti-PEG antibody titers between 32 and 512 were seen in 3.3 and 0.2%, respectively. During hyposensitization with monomethoxy polyethylene glycol modified ragweed extract and honey bee venom, respectively, the patients showed an anti-PEG antibody response. Titers of 32–512 were found in 50% of the patients directly after the first treatment course. After 2 years of treatment the percentage of patients with such titers declined to 28.5%. Mercaptoethanol treatment of sera indicated that the anti-PEG antibodies predominantly were of the IgM isotype. The weak IgM response found in treated patients is considered to be of no clinical significance.

Antibodies (ABS) against hydroxyethylstarch (HES) were raised in rabbits by immunization with HES-bovine serum albumin conjugate. ABS against HES were demonstrable by gel diffusion, passive hemagglutination (PH) and passive cutaneous anaphylaxis (PCA); specificity was confirmed by inhibition of PH and neutralization of PCA. No ABS against starch could be induced in comparative experiments. Non-immunogenicity of starch was attributed to its structural similarity with glycogen, widely distributed in animal species. Absence of cross-reactivity of anti-HES ABS with starch, amylopectin and glycogen and strong reactivity with 2-hydroxypropylstarch (DS = 0.65) and HES (DS = 0.7–1.2) indicate that hydroxyethyl substitution created antigenic determinants and conferred new immunochemical identity on the modified starch molecule. Anti-HES ABS represent specific analytical tools for the identification and quantitation of HES in biological material.

Dextran, a common plasma substitute, sometimes induces life-threatening hypersensitivity reactions. In this article Wolfgang Richter and Harriet Hedin discuss recent evidence that these Type III anaphylactic reactions, caused by natural antibodies, can be abolished by pretreatment o f patients with monovalent hapten dextran.

The immunogenicity of a sodium hyaluronate preparation for clinical use (Healon, Healonid, Pharmacia AB, Sweden) in ophthalmology and certain joint diseases has been tested in man. For immunization, two subcutaneous injections of 10 mg of sodium hyaluronate were given at an interval of 1 week. The following criteria were used as indicators of immunogenicity: skin prick test, microprecipitation test and complement analyses. No evidence for immunogenic properties was obtained in any of these tests. This refers to sodium hyaluronate itself and to the trace amounts of protein components contained in the preparation.