Immunological profile changes reflect milk oral immunotherapy outcomes
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Baseline and long-term milk component immunoglobulin profiles differed among children based on their responses to milk oral immunotherapy and long-term milk consumption, according to a study published in Allergy.
For example, there were associations between lower casein specific IgE levels at baseline and better outcomes, Tiina Kaisa Kauppila, MD, analytical chemist with the University of Helsinki Skin and Allergy Hospital, and colleagues wrote.
As research is ongoing to understand the immunological mechanism of OIT and better characterize the patients who will benefit, Kauppila and colleagues sought to longitudinally determine sIgE, sIgG4, sIgG4/IgE ratio and sIgA response to milk-specific components related to long-term outcomes of milk OIT.
The study involved 168 children aged 5 years and older undergoing OIT for a challenge-confirmed IgE-mediated milk allergy and 18 children with a milk allergy who were not undergoing OIT.
The OIT group included 96 patients (57%) on a high dose of at least 200 mL of milk daily as part of their OIT, 30 (18%) on a low dose of 10 mL to 199 mL of milk daily, and 42 (25%) who discontinued treatment and stopped consuming milk.
The researchers collected data before treatment, after buildup or 3 months after reaching the maintenance phase, and during the long-term follow-up between 1 and 11 years later (median, 6 years).
The group that had discontinued treatment — or the avoidance group — had the highest sIgE levels, with 76% having a baseline casein sIgE value of 17 kUA/L or greater. By comparison, 73% of the high-dose group had a baseline casein sIgE level of less than 17 kUA/L, and 80% of them had a value less than 28 kUA/L.
The high-dose group had higher milk component ratios of sIgG4 to sIgE at baseline than the low-dose group (P < .001) and the avoidance group (P = .04) in addition to having the lowest casein sIgG4 at baseline compared with the other groups (P = .01). The researchers noted that sIgG4/IgE ratio distinguished long-term outcomes at early timepoints.
Also, milk component sIgG4 appeared to increase in the post-buildup phase, where the high-dose group had higher milk component sIgG4 ratios than the low-dose (P < .001) and the avoidance (P = .003) groups.
The high-dose group additionally had the lowest milk protein and milk component sIgE of the groups (P < .001), whereas the low-dose group had the highest casein IgG4/IgE ratio (P = .002) in the long term.
During the treatment phase, median casein sIgA increased among all groups, with the high-dose group showing significantly greater concentrations than the other groups at the long-term time point (P = .002).
The group of patients who declined milk OIT included two (11%) who outgrew their milk allergy by the long-term time point, whereas 56% of the patients who underwent milk OIT consumed at least 200 mL of milk daily in the long term (P < .001).
When the researchers administered open milk challenges to 25 patients in the low-dose and avoidance groups at the long-term time point, the 13 patients with positive results had statistically higher baseline milk (P = .02), casein (P = .001) and beta-lactoglobulin (P = .007) sIgE concentrations than the 12 patients with negative results.
The patients with positive results also had statistically higher long-term milk component sIgE concentrations. The group that had negative results had higher casein and beta-lactoglobulin sIgG4/IgE ratios at baseline than the group with positive results (P = .002; P = .01) and in the long term (P = .007; P = .01).
Analysis of data from the 108 patients who provided samples at all three time points revealed a cluster of sensitization to casein sIgE among patients from the avoidance group and more prominent sensitization to beta-lactoglobulin and alpha-lactalbumin among patients from the high-dose group.
Overall, the researchers concluded that patients who use OIT for milk allergies begin treatment with variable immunological paths that may define their outcomes.
Perspective
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There is a definite need for additional data about long-term outcomes related to OIT and for a better understanding of predictors of food allergy treatment outcomes. This study aims to address these knowledge gaps.
Overall, the authors found that lower casein sIgE levels were associated with better outcomes. The findings were not surprising, as some prior studies have shown casein to be a marker of persistent cow’s milk allergy. However, there is variability in immunologic outcomes seen in OIT trials.
An unmentioned significant limitation of this study is that milk consumption at follow-up was self-reported with no details provided other than high dose, low dose or avoidance. Home introduction of an allergen after OIT can be complex and impacted by many factors other than reactions, including taste, food preferences and anxiety.
The authors attempted to address this by offering oral food challenges to the low-dose or avoidance group, but only 35% of eligible participants completed these challenges. Therefore, we do not know if lower milk consumption was due to tolerability and a lower reaction threshold or various other reasons.
In addition, the large sample size of this study was a strength, but there were large gaps in who had immunologic and long-term follow-up data.
This interesting study provided much needed long-term follow-up data after completing milk OIT. Additional long-term OIT follow-up studies are needed to see if these findings are replicated in other populations and to more clearly understand the reasons for the self-reported amounts consumed.
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