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一名患有抗白细胞介素-6自身抗体的儿童反复出现葡萄球菌性蜂窝织炎和皮下脓肿。

Recurrent staphylococcal cellulitis and subcutaneous abscesses in a child with autoantibodies against IL-6.

作者信息

Puel Anne, Picard Capucine, Lorrot Mathie, Pons Charlotte, Chrabieh Maya, Lorenzo Lazaro, Mamani-Matsuda Maria, Jouanguy Emmanuelle, Gendrel Dominique, Casanova Jean-Laurent

机构信息

Laboratoire de Génétique Humaine des Maladies Infectieuses, Institut National de la Santé et de la Recherche Médicale, U550, Paris, France.

出版信息

J Immunol. 2008 Jan 1;180(1):647-54. doi: 10.4049/jimmunol.180.1.647.

DOI:10.4049/jimmunol.180.1.647
PMID:18097067
Abstract

We investigated an otherwise healthy patient presenting two episodes of staphylococcal cellulitis and abscesses, accompanied by high fever and biological signs of inflammation but, paradoxically, with no detectable increase in serum levels of C-reactive protein (CRP), an IL-6-responsive protein synthesized in the liver. Following in vitro activation of whole blood cells from the patient with multiple cytokines, TLR agonists, heat-killed bacteria, and mitogens, we observed a profound and specific impairment of IL-6 secretion. However, the patient's PBMCs, activated in the same conditions but in the absence of the patient's plasma, secreted IL-6 normally. The patient's serum contained high titers of IgG1 autoantibodies against IL-6, which specifically neutralized IL-6 production by control PBMCs as well as IL-6 responses in the human hepatocellular carcinoma cell line Hep3B. These anti-IL-6 autoantibodies were detected over a period of 4 years, in the absence of any other autoantibodies. Our results indicate that these Abs probably prevented an increase in CRP concentration during infection and that impaired IL-6-mediated immunity may have contributed to staphylococcal disease. Patients with severe bacterial infections and low serum CRP concentrations should be tested for anti-IL-6 autoantibodies, especially in the presence of other clinical and biological signs of inflammation.

摘要

我们研究了一位原本健康的患者,该患者出现了两起葡萄球菌蜂窝织炎和脓肿,伴有高热及炎症的生物学体征,但矛盾的是,其血清中C反应蛋白(CRP)水平并未检测到升高,CRP是一种在肝脏中合成的白细胞介素6(IL-6)反应性蛋白。在用多种细胞因子、Toll样受体(TLR)激动剂、热灭活细菌和丝裂原对该患者的全血细胞进行体外激活后,我们观察到IL-6分泌存在严重且特异性的受损。然而,在相同条件下但无该患者血浆存在时激活的患者外周血单核细胞(PBMC)能正常分泌IL-6。该患者血清中含有高滴度的抗IL-6 IgG1自身抗体,这些抗体能特异性中和对照PBMC产生的IL-6以及人肝癌细胞系Hep3B中的IL-6反应。在4年的时间里均检测到了这些抗IL-6自身抗体,且未发现任何其他自身抗体。我们的结果表明,这些抗体可能在感染期间阻止了CRP浓度的升高,并且IL-6介导的免疫受损可能导致了葡萄球菌疾病。对于患有严重细菌感染且血清CRP浓度较低的患者,应检测其抗IL-6自身抗体,尤其是在存在其他临床和炎症生物学体征的情况下。

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