Valentine-Thon Elizabeth, Müller Kurt, Guzzi Gianpaolo, Kreisel Sybille, Ohnsorge Peter, Sandkamp Martin
Laboratory Center Bremen, Bremen, Germany.
Neuro Endocrinol Lett. 2006 Dec;27 Suppl 1:17-24.
Chronic low-level metal exposure may result in metal sensitization and undesirable side-effects. The main sources of metal exposure are from the environment or from corrosion of dental metal alloys. Affected patients are routinely diagnosed with the epicutaneous (patch) test. However, such testing may induce false-positive (irritative) reactions and may in itself sensitize or exacerbate symptoms. Alternatively, MELISA (Memory Lymphocyte ImmunoStimulation Assay), an optimized lymphocyte transformation test (LTT), can be used. In this study we analyzed the overall frequency and distribution of metal sensitization among symptomatic, metal-exposed patients. In addition, we determined the reproducibility of the assay and assessed its clinical relevance for detecting and monitoring hypersensitivity to metals.
To analyze the frequency and distribution of metal sensitization, blood from 700 consecutive patients was tested against a total of 26 metals in the validated LTT-MELISA. For reproducibility testing, 391 single metal tests from 63 patients were performed in parallel. Finally, to assess clinical relevance, 14 patients with known metal exposure showing local (dry mouth, Oral Lichen Planus, Burning Mouth Syndrome, eczema) and/or systemic (chronic infections, fatigue, autoimmune disorders, central nervous system disturbances, depression) effects were tested in LTT-MELISA. In 7 cases testing was repeated following removal of the allergy-causing metals or, in 2 additional cases, without therapeutic intervention.
Of the 700 patients tested, 74.6% responded to >/= 1 metal in LTT-MELISA, with a subgroup of 17.9% responding to >/= 3 metals. Reactivity was most frequent to nickel (68.2%), followed by cadmium (23.7%), gold (17.8%), palladium (12.7%), inorganic mercury (11.4%), molybdenum (10.8%), beryllium (9.7%), titanium dioxide (4.2%), lead (3.7%), and platinum (3.4%). Reproducibility was 94.9%, with most discordant results in a low-positive range. Removal of the alloys or prostheses containing allergenic metals resulted in remarkable clinical improvement correlating with a significant reduction or complete normalization of specific lymphocyte reactivity. In contrast, both LTT-MELISA reactivity and clinical symptoms remained unchanged in follow-up samples from the 2 patients who did not remove the source of metal exposure.
The optimized LTT-MELISA test is a clinically useful and reliable tool for identifying and monitoring metal sensitization in symptomatic metal-exposed individuals.
长期低水平接触金属可能导致金属致敏及不良副作用。金属接触的主要来源是环境或牙科金属合金的腐蚀。受影响的患者通常通过表皮（斑贴）试验进行诊断。然而，这种检测可能会引发假阳性（刺激性）反应，并且其本身可能会使症状致敏或加重。另外，可以使用MELISA（记忆淋巴细胞免疫刺激试验），这是一种优化的淋巴细胞转化试验（LTT）。在本研究中，我们分析了有症状的、接触金属的患者中金属致敏的总体频率和分布情况。此外，我们确定了该检测方法的可重复性，并评估了其在检测和监测金属超敏反应方面的临床相关性。
为了分析金属致敏的频率和分布情况，在经过验证的LTT - MELISA中，对700例连续患者的血液进行了总共26种金属的检测。为了进行可重复性测试，对来自63例患者的391次单一金属检测进行了平行操作。最后，为了评估临床相关性，对14例已知接触金属且出现局部（口干、口腔扁平苔藓、灼口综合征、湿疹）和/或全身（慢性感染、疲劳、自身免疫性疾病、中枢神经系统紊乱、抑郁）症状的患者进行了LTT - MELISA检测。在7例患者中，去除引起过敏的金属后重复进行检测，另外2例患者未进行治疗干预。
在接受检测的700例患者中，74.6%的患者在LTT - MELISA中对≥1种金属有反应，其中17.9%的亚组患者对≥3种金属有反应。反应最常见于镍（68.2%），其次是镉（23.7%）、金（17.8%）、钯（12.7%）、无机汞（11.4%）、钼（10.8%）、铍（9.7%）、二氧化钛（4.2%）、铅（3.7%）和铂（3.4%）。可重复性为94.9%，大多数不一致的结果处于低阳性范围。去除含有致敏金属的合金或假体后，临床症状显著改善，同时特异性淋巴细胞反应性显著降低或完全恢复正常。相比之下，在未去除金属接触源的2例患者的随访样本中，LTT - MELISA反应性和临床症状均未改变。
优化后的LTT - MELISA检测是一种在临床上有用且可靠的工具，可用于识别和监测有症状的、接触金属的个体中的金属致敏情况。
