Hatcher Vishaka R, Caballero Manuel Y, Schuldt Meredith M, Adams Karla E
From the Department of Allergy & Immunology, Wilford Hall Ambulatory Surgical Center, Joint Base San Antonio - Lackland, Texas and.
Department of Cell Biology, 59th Medical Wing Chief Scientist's Office, Science and Technology, Clinical Investigations and Research Support Program, Joint Base San Antonio - Lackland, Texas.
Allergy Asthma Proc. 2025 Sep 1;46(5):431-437. doi: 10.2500/aap.2025.46.250047.
Sporadic reports have been published with regard to allergic reactions in patients with bovine milk allergy after receiving parenteral lactose-containing methylprednisolone. Persistent milk allergy is a risk factor for other atopic diseases, in which corticosteroids, methylprednisolone, are commonly an adjunctive treatment. Laboratory investigations to validate the presence of residual milk protein as the cause for reactions are scarce. Thus, individualized recommendations for the use of methylprednisolone in patients with milk allergy remain undefined. We hypothesized that excipient contaminants, e.g., residual caseins, may be responsible for these reactions. We sought to evaluate for the presence of casein proteins in lactose-containing methylprednisolone and provide recommendations with regard to its use in patients with milk allergy. To assess for incomplete purification of lactose from its bovine milk source, standardized enzyme-linked immunosorbent assay (ELISA) was performed from five vials across four lots of commercially available lactose-containing methylprednisolone to detect casein subtypes Bos d 9 and Bos d 11, the two most abundant milk proteins. High-fidelity ELISA revealed no detectable Bos d 9 in any vials of lactose-containing methylprednisolone. Trace amounts of Bos d 11 were detected in all vials compared with Bos d 9 (p = 0.008). Molecular modeling revealed minimal similarity between Bos d 9 and Bos d 11. Undetectable Bos d 9 and trace Bos d 11 in lactose-containing methylprednisolone raises optimism but warrants further investigation of immunoglobulin E binding epitopes and the clinical relevance of casein subtypes. It is reassuring that milk protein eliciting doses are usually 10-fold higher than the nanogram quantities of Bos d 11 detected in our study, although this is limited by exposure route. Vaccines and medications with possible trace milk proteins remain largely well tolerated in patients with milk allergy. Lactose-containing methylprednisolone can likely be used with low risk of adverse reaction in most patients with milk allergy.
关于牛奶过敏患者在接受含乳糖的肠胃外注射甲泼尼龙后出现过敏反应的零星报告已经发表。持续性牛奶过敏是其他特应性疾病的一个危险因素，在这些疾病中，皮质类固醇（甲泼尼龙）通常作为辅助治疗药物。用于验证残留牛奶蛋白是否为反应原因的实验室研究很少。因此，对于牛奶过敏患者使用甲泼尼龙的个体化建议仍不明确。我们推测辅料污染物，例如残留酪蛋白，可能是这些反应的原因。我们试图评估含乳糖的甲泼尼龙中酪蛋白的存在情况，并就其在牛奶过敏患者中的使用提供建议。为了评估乳糖从牛奶来源中未完全纯化的情况，对来自四个批次市售含乳糖甲泼尼龙的五个小瓶进行了标准化酶联免疫吸附测定（ELISA），以检测两种最丰富的牛奶蛋白酪蛋白亚型Bos d 9和Bos d 11。高保真ELISA显示，在任何含乳糖甲泼尼龙小瓶中均未检测到Bos d 9。与Bos d 9相比，在所有小瓶中均检测到痕量的Bos d 11（p = 0.008）。分子建模显示Bos d 9和Bos d 11之间的相似性极小。含乳糖甲泼尼龙中未检测到Bos d 9和痕量的Bos d 11令人感到乐观，但仍需进一步研究免疫球蛋白E结合表位以及酪蛋白亚型的临床相关性。令人放心的是，引发过敏反应的牛奶蛋白剂量通常比我们研究中检测到的纳克量的Bos d 11高10倍，尽管这受到暴露途径的限制。对于牛奶过敏患者，含有可能痕量牛奶蛋白的疫苗和药物在很大程度上仍具有良好的耐受性。大多数牛奶过敏患者使用含乳糖的甲泼尼龙时可能不良反应风险较低。
