Anti-myeloperoxidase and anti-cathepsin G antibodies in sulphonamide hypersensitivity.
Anti-myeloperoxidase and anti-cathepsin G antibodies in sulphonamide hypersensitivity.
复制标题
磺胺超敏反应中的抗髓过氧化物酶和抗组织蛋白酶 G 抗体。
DOI：
10.1111/j.1365-2222.2007.02845.x
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Trepanier,LA
中科院分区：
文献类型：
--
作者：
Lavergne,SN;Drescher,NJ;Trepanier,LA
抗中性粒细胞胞浆抗体（anti - neutrophil cytoplasmic antibodies， ANCA）与人类血管炎有关。磺胺类抗菌剂引起药物超敏反应，伴有提示血管炎的一些临床体征。目的以犬为自发性临床模型，研究磺胺类HS是否与抗中性粒细胞抗体相关。方法34只磺胺- HS犬、11只磺胺-耐受犬和9只健康的磺胺- naïve犬，采用商用ELISA法检测人髓过氧化物酶（MPO）的抗中性粒细胞抗体，采用商用人ANCA Western blot方法，采用免疫印迹法检测犬全中性粒细胞。结果ELISA检测结果显示，抗MPO抗体在HS犬中出现的频率（50%）明显高于耐药犬（18%），而耐药犬的吸光度也明显较低。在HS犬中，与存活犬（35%）相比，未存活HS反应犬（78%）的抗MPO抗体明显更常见，吸光度明显更高。使用免疫印迹法，在HS和“耐受”犬中检测到的ANCA总体频率相似。然而，有一种蛋白被几种HS犬靶向，但没有“耐受”犬，被鉴定为组织蛋白酶G。结论这些数据表明抗MPO抗体和抗组织蛋白酶G抗体与磺胺类HS有关。抗MPO抗体已被证明在体外和体内都具有致病性，可导致血管炎病变和血管炎样综合征。因此，本研究提示血管炎可能是这种磺胺类HS的组织损伤机制之一。此外，在人类磺胺类药物HS患者中，应考虑ANCA的评估及其与疾病严重程度和临床结局的关系。
BackgroundAnti‐neutrophil cytoplasmic antibodies (ANCA) are associated with vasculitis in humans. Sulphonamide antimicrobials cause drug hypersensitivity (HS) reactions with some clinical signs that are suggestive of vasculitis.ObjectiveThe purpose of this study was to determine whether sulphonamide HS is associated with anti‐neutrophil antibodies, using the dog as a spontaneous clinical model.MethodsThirty‐four sulphonamide‐HS dogs, 11 sulphonamide‐‘tolerant’ dogs, and nine healthy sulphonamide‐naïve dogs were evaluated for anti‐neutrophil antibodies using a commercial ELISA against human myeloperoxidase (MPO), a commercial human ANCA Western blot protocol, and immunoblotting against whole canine neutrophils.ResultsUsing ELISA, anti‐MPO antibodies were found with an apparent higher frequency in HS dogs (50%), compared with ‘tolerant’ dogs (18%), which also showed significantly lower absorbances. Among HS dogs, anti‐MPO antibodies were significantly more common, with significantly higher absorbances, in dogs that did not survive the HS reaction (78%) compared with survivors (35%). Using immunoblotting, ANCA were detected with similar overall frequencies in HS and ‘tolerant’ dogs. However, one protein targeted by several HS dogs, but no ‘tolerant’ dogs, was identified as cathepsin G.ConclusionThese data indicate that anti‐MPO antibodies and anti‐cathepsin G antibodies are associated with sulphonamide HS. Anti‐MPO antibodies have been shown to be pathogenic bothin vitroandin vivo, leading to vasculitis lesions and vasculitis‐like syndromes. The present study therefore suggests that vasculitis might be one mechanism of tissue damage in this sulphonamide HS. Furthermore, the evaluation of ANCA, and its relationship to disease severity and clinical outcome, should be considered in human patients with sulphonamide drug HS.