Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Allergy Clin Immunol. 2012 Feb;129(2):448-55, 455.e1-5. doi: 10.1016/j.jaci.2011.10.023. Epub 2011 Nov 30.
Oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are potential therapies for food allergy, but the optimal method of administration, mechanism of action, and duration of response remain unknown.
We sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow's milk (CM) allergy.
We randomized children with CM allergy to SLIT alone or SLIT followed by OIT. After screening double-blind, placebo-controlled food challenges and initial SLIT escalation, subjects either continued SLIT escalation to 7 mg daily or began OIT to either 1000 mg (the OITB group) or 2000 mg (the OITA group) of milk protein. They were challenged with 8 g of milk protein after 12 and 60 weeks of maintenance. If they passed the 60-week challenge, therapy was withdrawn, with challenges repeated 1 and 6 weeks later. Mechanistic correlates included end point titration skin prick testing and measurement of CM-specific IgE and IgG(4) levels, basophil histamine release, constitutive CD63 expression, CD203c expression, and intracellular spleen tyrosine kinase levels.
Thirty subjects with CM allergy aged 6 to 17 years were enrolled. After therapy, 1 of 10 subjects in the SLIT group, 6 of 10 subjects in the SLIT/OITB group, and 8 of 10 subjects in the OITA group passed the 8-g challenge (P = .002, SLIT vs OIT). After avoidance, 6 of 15 subjects (3 of 6 subjects in the OITB group and 3 of 8 subjects in the OITA group) regained reactivity, 2 after only 1 week. Although the overall reaction rate was similar, systemic reactions were more common during OIT than during SLIT. By the end of therapy, titrated CM skin prick test results and CD63 and CD203c expression decreased and CM-specific IgG(4) levels increased in all groups, whereas CM-specific IgE and spontaneous histamine release values decreased in only the OIT group.
OIT was more efficacious for desensitization to CM than SLIT alone but was accompanied by more systemic side effects. Clinical desensitization was lost in some cases within 1 week off therapy.
口服免疫疗法（OIT）和舌下免疫疗法（SLIT）是治疗食物过敏的潜在疗法，但最佳给药方法、作用机制和反应持续时间仍不清楚。
我们旨在探索 OIT 和 SLIT 治疗牛奶（CM）过敏的安全性和有效性。
我们将 CM 过敏的儿童随机分为单独 SLIT 或 SLIT 后进行 OIT。在进行双盲、安慰剂对照的食物挑战和初始 SLIT 升级后，受试者要么继续升级到每日 7 毫克 SLIT，要么开始接受 OIT，分别接受 1000 毫克（OITB 组）或 2000 毫克（OITA 组）的牛奶蛋白。在维持 12 周和 60 周后，他们接受 8 克牛奶蛋白的挑战。如果他们通过了 60 周的挑战，则停止治疗，并在 1 周和 6 周后重复挑战。机制相关性包括终点滴定皮肤点刺试验以及测量 CM 特异性 IgE 和 IgG（4）水平、嗜碱性粒细胞组胺释放、组成型 CD63 表达、CD203c 表达和细胞内脾酪氨酸激酶水平。
招募了 30 名年龄在 6 至 17 岁之间的 CM 过敏儿童。治疗后，SLIT 组有 1/10 名受试者、SLIT/OITB 组有 6/10 名受试者和 OITA 组有 8/10 名受试者通过了 8 克挑战（P=0.002，SLIT 与 OIT）。在避免后，15 名受试者中有 6 名（OITB 组有 3 名，OITA 组有 3 名）恢复了反应性，其中 2 名仅在 1 周后恢复。尽管总体反应率相似，但 OIT 期间的全身反应比 SLIT 期间更常见。到治疗结束时，所有组的 CM 皮肤点刺试验结果、CD63 和 CD203c 表达均降低，CM 特异性 IgG（4）水平升高，而仅 OIT 组的 CM 特异性 IgE 和自发性组胺释放值降低。
OIT 比单独 SLIT 更有效治疗 CM 脱敏，但伴有更多的全身副作用。在停止治疗后的 1 周内，一些病例的临床脱敏作用消失。
