Recurrent Staphylococcal cellulitis and subcutaneous abscesses in a child with autoantibodies against IL-6
Recurrent Staphylococcal cellulitis and subcutaneous abscesses in a child with autoantibodies against IL-6
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DOI：
10.4049/jimmunol.180.1.647
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发表时间：
2008-01-01
影响因子：
4.4
通讯作者：
Casanova, Jean-Laurent
中科院分区：
文献类型：
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作者：
Puel, Anne;Picard, Capucine;Casanova, Jean-Laurent
我们研究了一个健康的病人，表现为两次葡萄球菌蜂窝织炎和脓肿发作，伴有高热和炎症的生物学体征，但矛盾的是，血清G反应蛋白（CRP）水平没有检测到增加，一种IL-6反应蛋白在肝脏中合成。用多种细胞因子、TLR激动剂、热灭活细菌和有丝分裂原体外活化患者的全血细胞后，我们观察到IL-6分泌的深刻和特异性损伤。然而，在相同条件下但在不存在患者血浆的情况下激活的患者PBMC正常分泌IL-6。患者血清中含有高滴度的抗IL-6的IgG 1自身抗体，其特异性中和对照PBMC产生的IL-6以及人肝细胞癌细胞系Hep 3B中的IL-6应答。这些抗IL-6自身抗体在4年的时间内检测到，在没有任何其他自身抗体。我们的研究结果表明，这些抗体可能阻止了感染过程中CRP浓度的增加，IL-6介导的免疫功能受损可能导致葡萄球菌疾病。严重细菌感染和低血清CRP浓度的患者应检测抗IL-6自身抗体，特别是在存在其他炎症临床和生物学体征的情况下。
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 G-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.