Wanting Qi,1,2,3# Jialing Chen,4# Huishuang Zheng,1,2,3 Wenjing Zhu,4 Kai Guan,1,2,3 Li Sha4

Affiliations:
1 Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
2 Peking Union Medical College, Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment of Allergic Disease, Beijing, China
3 National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
4 Department of Allergy, Children’s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China

#These authors contributed equally to this manuscript.

Abstract

Background: Cow’s milk allergy (CMA) is one of the most common food allergies in young children. As improved diagnostic tools, allergic tests are inconsistent and limited in predicting anaphylaxis.
Objective: To explore risk factors for anaphylaxis and to determine practical cut-offs for allergic tests in predicting anaphylaxis.
Methods: This is a prospective cohort study. Children with IgE-mediated CMA were enrolled and divided into three groups (Group 1: non-anaphylaxis; Group 2: GRADE I anaphylaxis; Group 3: GRADE II-IV anaphylaxis that warranted epinephrine). Prick-to-prick tests (PTPs) using fresh cow’s milk (CM) were performed. Serum specific IgE (sIgE) against CM and its components, including casein, alpha-lactalbumin, beta-lactoglobulin, and bovine serum albumin were measured. The 90% and 95% positive predictive value (PPV) decision points for predicting anaphylaxis were determined. Potential predictors of anaphylaxis were evaluated in logistic regression models.
Results: This study included 134 CMA patients with a median age of 14.4 months. The sensitization rate to any CM component was 89%. Group 3 was more likely to be sensitized to multiple CM components and have higher sIgE levels. The 95% PPV diagnostic decision points of casein-sIgE in predicting anaphylaxis was 13.0 kUA/L. For GRADE II-IV anaphylaxis, casein-sIgE ≥ 54.9 kUA/L could provide a PPV of 88.9%. The elevated casein-sIgE level (OR 14.0, P = 0.025) and complicating respiratory allergic diseases (OR 4.8, P = 0.022) were independent risk factors for GRADE II-IV anaphylaxis.
Conclusion: High casein-sIgE levels are strongly associated with CM anaphylaxis. Detection of casein-sIgE may offer an additional value for the prediction of CM anaphylaxis.
Key words: casein, IgE-mediated cow’s milk allergy, specific IgE, anaphylaxis, specificity, positive predictive value