Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Anesth Analg. 2010 May 1;110(5):1310-7. doi: 10.1213/ANE.0b013e3181d7e31c.
In health care workers, the natural rubber latex (NRL) allergy phenotype has been shown to be associated with promoter polymorphisms in interleukins 13 and 18 (IL13 and IL18) when compared with nonatopic controls. However, it is not known whether high-risk patient populations, such as those born with neural tube defects or genitourinary abnormalities, demonstrate a heightened propensity toward the same genetic/immunologic risk factors that have been reported for health care workers. In this study, we tested the hypothesis that single-nucleotide polymorphisms in genes encoding IL13 and IL18 occur at an increased frequency in NRL allergic patients with spina bifida (SB) or bladder exstrophy (BE).
One hundred twenty subjects (40 SB, 40 BE, and 40 control) were screened using a clinical history questionnaire and NRL-specific immunoglobulin E (IgE) antibody measurements in the blood. Genomic DNA was extracted from peripheral blood lymphocytes and analyzed for single-nucleotide polymorphisms in candidate genes of interest. Univariate and multivariate analyses were performed to identify significant variables with significance defined as P < 0.05.
Sensitization (IgE antibody positivity) to NRL allergens was associated with atopic history and number of prior operations and was prevented by the avoidance of NRL beginning at birth. However, unlike health care workers, the NRL allergy phenotype was not significantly associated with promoter polymorphisms in IL13 or IL18 when comparing NRL allergic SB and BE patients with nonsensitized patients and with atopic and nonatopic controls.
In patients born with SB or BE, environmental factors seem to play a greater role in the development of NRL sensitization and overt allergic symptoms than the IL polymorphisms in IL13 and IL18 previously shown to be associated with NRL allergy in health care workers.
与非过敏对照相比,在健康医护人员中,已经证明天然橡胶乳胶 (NRL) 过敏表型与白细胞介素 13 和 18 (IL13 和 IL18) 的启动子多态性相关。然而,目前尚不清楚高危患者群体,如出生时患有神经管缺陷或泌尿生殖系统异常的患者,是否表现出对已报道的与健康医护人员 NRL 过敏相关的相同遗传/免疫危险因素的更高倾向性。在这项研究中,我们检验了这样一个假设,即在患有脊柱裂 (SB) 或膀胱外翻 (BE) 的 NRL 过敏患者中,编码白细胞介素 13 和 18 的基因中的单核苷酸多态性发生的频率增加。
通过临床病史问卷和血液中 NRL 特异性免疫球蛋白 E (IgE) 抗体测量,对 120 名受试者 (40 名 SB、40 名 BE 和 40 名对照) 进行了筛选。从外周血淋巴细胞中提取基因组 DNA,并对候选基因中的单核苷酸多态性进行分析。进行单变量和多变量分析以确定具有统计学意义的变量,显著性定义为 P < 0.05。
对 NRL 过敏原的致敏 (IgE 抗体阳性) 与特应性病史和既往手术次数有关,并且从出生开始避免接触 NRL 可以预防致敏。然而,与健康医护人员不同的是,在比较 NRL 过敏的 SB 和 BE 患者与未致敏患者以及特应性和非特应性对照时,NRL 过敏表型与白细胞介素 13 或白细胞介素 18 的启动子多态性无显著相关性。
在出生时患有 SB 或 BE 的患者中,环境因素似乎在 NRL 致敏和明显过敏症状的发展中发挥了更大的作用,而不是以前在健康医护人员中与 NRL 过敏相关的白细胞介素 13 和白细胞介素 18 中的 IL 多态性。