Continuous cow's milk protein ingestion during infancy may promote casein-specific IgG4 production

Tetsuhiro Sakihara; Kenta Otsuji; Yohei Arakaki; Kazuya Hamada; Shiro Sugiura; Komei Ito

doi:10.1016/j.jacig.2024.100257

Continuous cow's milk protein ingestion during infancy may promote casein-specific IgG4 production

J Allergy Clin Immunol Glob. 2024 Apr 10;3(3):100257. doi: 10.1016/j.jacig.2024.100257. eCollection 2024 Aug.

Authors

Tetsuhiro Sakihara¹, Kenta Otsuji², Yohei Arakaki³, Kazuya Hamada⁴, Shiro Sugiura⁵, Komei Ito⁵

Affiliations

¹ Department of Pediatrics, Heartlife Hospital, Okinawa, Japan.
² Department of Pediatrics, Okinawa Kyodo Hospital, Okinawa, Japan.
³ Department of Pediatrics, Naha City Hospital, Okinawa, Japan.
⁴ Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
⁵ Department of Allergy, Aichi Children's Health and Medical Center, Aichi, Japan.

Abstract

Background: Early supplementation and subsequent discontinuation of cow's milk formula (CMF) may increase the risk of cow's milk allergy in breast-fed infants, but little is known about the relationship between continuous CMF ingestion and cow's milk protein-specific immunoglobulin production.

Objective: This study aimed to clarify the aforesaid relationship in cow's milk-sensitized infants.

Methods: Using data from a randomized controlled trial of a Japanese birth cohort, we performed a subgroup analysis of participants who had ingested CMF in the first 3 days of life and exhibited a positive skin prick test response to cow's milk at age 6 months. We compared the differences in median titers of cow's milk-specific IgE, casein-specific IgE, and casein-specific IgG4 levels between participants who continued daily or intermittent CMF ingestion up to age 6 months (the "continuous group") and participants who discontinued CMF ingestion before age 6 months (the "discontinued group").

Results: From among 462 trial participants, 49 (10.6%) were included in this study (21 in the continuous group and 29 in the discontinued group). The median titer of cow's milk-specific IgE was 0.17 kUA/L (interquartile range [IQR] = <0.10 to 0.57) in the continuous group and 0.66 kUA/L (IQR = 0.49-1.18) in the discontinued group (P = .0008). The median titer of casein-specific IgE was <0.10 kUA/L (IQR = <0.10 to 0.15) in the continuous group and <0.10 kUA/L (IQR = <0.10 to 0.37) in the discontinued group (P = .51). The median titer of casein-specific IgG4 was 2.58 mg_A/L (IQR = 0.77-6.73) in the continuous group and 0.09 mg_A/L (IQR = 0.07-0.13) in the discontinued group (P < .0001).

Conclusion: Continuous CMF ingestion may promote casein-specific IgG4 production in cow's milk-sensitized infants.

Keywords: Food allergy; IgG4; cow’s milk formula; early introduction; infant formula; milk allergy; prevention; randomized controlled trial; sensitization.