Evaluation of the usefulness of lymphocyte proliferation assays in the diagnosis of allergy to cow's milk
Evaluation of the usefulness of lymphocyte proliferation assays in the diagnosis of allergy to cow's milk
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DOI：
10.1016/s0091-6749(97)70054-x
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发表时间：
1997-03-01
影响因子：
14.2
通讯作者：
Sampson, HA
中科院分区：
文献类型：
--
作者：
Hoffman, KM;Ho, DG;Sampson, HA
背景资料：细胞介导的机制在IgE介导的牛奶过敏（IgE-MA）和牛奶诱导的小肠结肠炎综合征（ME）中的意义是有争议的，一些研究者声称淋巴细胞增殖测定在食物过敏的诊断中是有用的，尽管研究设计和报告的结果存在很大差异，本研究旨在解决这些变量中的许多变量，以确定淋巴细胞增殖试验是否与临床诊断相关。在两组儿童中评价了对牛奶抗原的淋巴细胞增殖反应，其中27例为IgE-MA，9例为ME，21例为儿科对照组。通过阳性双盲、安慰剂对照食物激发和阳性皮肤点刺试验结果记录IgE介导的食物过敏，通过口服激发或摄入牛奶后反复发作延迟呕吐（> 2小时）和阴性皮肤点刺试验反应诊断ME。分离和培养外周血单个核细胞，用牛奶刺激培养物（感兴趣的食物抗原），大豆抗原（一种不相关的食物抗原）或破伤风抗原在第5、7和9天，用氚标记的胸苷脉冲细胞并孵育4小时，结果以每分钟计数（cpm）和刺激指数（SI）进行比较。通常在第7天观察到最大增殖。中值cpm（20，941）和SI中位数27例IgE-MA患儿对乳汁抗原的反应性（19.2）显著高于对照组（6969 cpm; SI = 14.2; p = 0.001和p < 0.05），然而，范围很大，广泛重叠（IgE-MA，5616至52，053 cpm;对照组，469至39，260 cpm），当比较cpm时，非大豆过敏的IgE-MA患者对大豆抗原的反应也显著高于对照组（0.01 < p < 0.05）。ME患者的背景和对破伤风抗原的反应无差异，（11，975 cpm）显著高于对照组（6969 cpm; 0.01 < p < 0.05），比较cpm时，而仅比较SI时，二者无显著性差异。总体而言，这些结果表明淋巴细胞增殖试验既不能诊断也不能预测牛奶过敏个体患者的临床反应性。许多对照患者的淋巴细胞对牛奶抗原具有高度反应性，而许多牛奶过敏患者的淋巴细胞则不具有高度反应性。仅当将患者作为组进行比较时，统计学显著性差异才是明显的。
Background: The significance of cell-mediated mechanisms in IgE-mediated milk allergy (IgE-MA) and in milk-induced enterocolitis syndrome (ME) is controversial, Some investigators have claimed that lymphocyte proliferation assays are useful in the diagnosis of food hypersensitivity, despite the great variability in study designs and results reported, This study was undertaken to address many of these variables slid to determine whether lymphocyte proliferation assays correlate with clinical diagnoses.Methods: Lymphocyte proliferative responses to milk antigen were evaluated in two groups of children, 27 with IgE-MA, and nine with ME and in 21 pediatric control subjects. IgE-mediated food allergy was documented by positive double-blind, placebo-controlled food challenges and positive skin prick test results, ME was diagnosed by oral challenge or by a history of repeated episodes of delayed vomiting (> 2 hours) after ingestion of milk and by negative skin prick test responses. Peripheral blood mononuclear cells were isolated and cultured, Cultures stimulated with milk (the food antigen of interest), soy antigen (a nonrelevant food antigen), or tetanus antigen (a positive control antigen) and unstimulated controls were performed in quadruplicate, On days 5, 7, and 9, cells were pulsed with tritium-labeled thymidine and incubated for 4 hours, Results were compared as counts per minute (cpm) and as stimulation indices (SIs).Results: Maximal proliferation was generally seen on day 7, The median cpm (20,941) and the median SI (19.2) in response to milk antigen in the 27 children with IgE-MA were significantly greater than those in the control patients (6969 cpm; SI = 14.2; p = 0.001 and p < 0.05, respectively), However, the ranges mere large and overlapped extensively (IgE-MA, 5616 to 52,053 cpm; controls, 469 to 39,260 cpm), The non-soy-allergic patients with IgE-MA also had a significantly greater response to soy antigen than did the control subjects when cpm were compared (0.01 < p < 0.05). There were no differences in background or in response to tetanus antigen, The median response to milk in the patients with ME (11,975 cpm) was significantly greater than that in control subjects (6969 cpm; 0.01 < p < 0.05), when cpm were compared but not when SIs mere compared, There were no significant differences between the patients with IgE-MA and those with ME.Conclusion: Overall, these results indicate that lymphocyte proliferation assays are neither diagnostic nor predictive of clinical reactivity in individual patients with milk allergy, Lymphocytes of many control patients are highly responsive to milk antigens, and lymphocytes of many patients with milk allergy are not, Statistically significant differences are only evident when the patients are compared as groups.