Endotyping Non–IgE-mediated Immunoreactivity to Polyethylene Glycol: Implications for Allergic Patients

Background: Several publications report polyethylene glycols (PEGs) and PEGylated therapeutics as responsible for non–IgE-mediated allergic reactions. There is no standardized lab exam that can endotype (quantify the participation of these mechanisms inside each patient’s pattern of symptoms) besides in vivo provocation tests.

Objective and Aim: To evaluate the Tube Titration of Precipitins (TTP) and the Leukocyte Adherence Inhibition Test (LAIT) to discriminate and endotype non–IgE-mediated immunoreactivity against a PEGs solution in patients with non–IgE-mediated allergic phenotypes.

Research Design and Research Protocol: To retrospectively examine the medical charts of two cohorts (with 100 patients each) diagnosed with non–IgE-mediated allergic rhinitis, allergic bronchitis, asthma, allergic sinus headache, atopic dermatitis, and/or urticaria who were investigated with the help of TTP or ex vivo challenge tests monitored by LAIT against PEGs.

Methodology: We identified the registered results of the semi-quantitative serum TTP against 1 mg/mL PEGs 4000 solution, which were distributed in ranges through a cascade distribution chart to outline the variability of the results inside the first cohort. The LAI done with the ex vivo challenges with 1 mg/mL PEGs 4000 solution were distributed in ranges through a cascade distribution chart The statistical characteristics of the two cohorts were calculated.

Results: The TTP showed a wide distribution range of results. The mean was estimated at 1:246; the median at 1:192; the standard deviation at 1:188. The LAIT showed a wide distribution range of results. The LAI ranged from 0% to 98%. The mean was 41.9%; the median was 45%; the standard deviation was 28.5%. The cascade distribution demonstrates a wide range of LAI results.

Conclusion: Some patients showed any or low immunoreactivity during the ex vivo challenge test, while most displayed moderate or strong immunoreactivity, which could reflect the participation of PEGs antibodies in a non–IgE-mediated hypersensitivity condition.