Center for Molecular Allergology, IDI-IRCCS, Rome, Italy.
PLoS One. 2012;7(7):e40945. doi: 10.1371/journal.pone.0040945. Epub 2012 Jul 19.
From patients' reports and our preliminary observations, a fully maturated cheese (Parmigiano-Reggiano; PR) seems to be well tolerated by a subset of cow's milk (CM) allergic patients.
To biochemically and immunologically characterize PR samples at different maturation stage and to verify PR tolerability in CM allergic children. Seventy patients, with suspected CM allergy, were enrolled. IgE to CM, α-lactalbumin (ALA), β-lactoglobulin (BLG) and caseins (CAS) were tested using ImmunoCAP, ISAC103 and skin prick test. Patients underwent a double-blind, placebo-controlled food challenge with CM, and an open food challenge with 36 months-maturated PR. Extracts obtained from PR samples were biochemically analyzed in order to determine protein and peptide contents. Pepsin and trypsin-chymotrypsin-pepsin simulated digestions were applied to PR extracts. Each PR extract was investigated by IgE Single Point Highest Inhibition Achievable assay (SPHIAa). The efficiency analysis was carried out using CM and PR oral challenges as gold standards.
The IgE binding to milk allergens was 100% inhibited by almost all PR preparations; the only difference was for CAS, mainly α(S1)-CAS. Sixteen patients sensitized to CM tolerated both CM and PR; 29 patients tolerated PR only; 21 patients, reacted to both CM and PR, whereas 4 patients reactive to CM refused to ingest PR. ROC analysis showed that the absence of IgE to BLG measured by ISAC could be a good marker of PR tolerance. The SPHIAa using digested PR preparations showed a marked effect on IgE binding to CAS and almost none on ALA and BLG.
58% of patients clinically reactive to CM tolerated fully maturated PR. The preliminary digestion of CAS induced by PR maturation process, facilitating a further loss of allergenic reactivity during gut digestion, might explain the tolerance. This hypothesis seems to work when no IgE sensitization to ISAC BLG is detected.
根据患者报告和我们的初步观察,成熟的奶酪(帕尔马干酪;PR)似乎被一部分牛奶过敏患者耐受。
对不同成熟阶段的 PR 样本进行生化和免疫分析,并验证 PR 在牛奶过敏儿童中的耐受性。共纳入 70 名疑似牛奶过敏的患者。使用 ImmunoCAP、ISAC103 和皮肤点刺试验检测 IgE 对牛奶、α-乳白蛋白(ALA)、β-乳球蛋白(BLG)和酪蛋白(CAS)的反应。患者接受了牛奶的双盲、安慰剂对照食物挑战和 36 个月成熟的 PR 的开放食物挑战。从 PR 样本中提取的提取物进行生化分析,以确定蛋白质和肽含量。应用胃蛋白酶和胰蛋白酶-糜蛋白酶-胃蛋白酶模拟消化对 PR 提取物进行处理。使用 IgE 单点最高抑制可实现分析(SPHIAa)对每个 PR 提取物进行研究。采用 CM 和 PR 口服挑战作为金标准进行效率分析。
PR 制剂几乎完全抑制了牛奶过敏原的 IgE 结合;唯一的区别是 CAS,主要是α(S1)-CAS。16 名对 CM 敏感的患者耐受 CM 和 PR;29 名患者仅耐受 PR;21 名患者对 CM 和 PR 均有反应,而 4 名对 CM 有反应的患者拒绝摄入 PR。ROC 分析表明,ISAC 检测到的 BLG 无 IgE 可作为 PR 耐受的良好标志物。使用消化的 PR 制剂进行的 SPHIAa 显示对 CAS 的 IgE 结合有明显影响,而对 ALA 和 BLG 几乎没有影响。
58%对 CM 临床反应的患者耐受完全成熟的 PR。PR 成熟过程中诱导的 CAS 初步消化,促进了在肠道消化过程中进一步丧失过敏反应性,可能解释了这种耐受性。当未检测到 ISAC BLG 的 IgE 致敏时,该假设似乎有效。