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Recurrent Staphylococcal Cellulitis and Subcutaneous Abscesses in a Child with Autoantibodies against IL-6¹

Anne Puel^2,*,, Capucine Picard^*,,, Mathie Lorrot^||, Charlotte Pons^||, Maya Chrabieh^*,, Lazaro Lorenzo^*,, Maria Mamani-Matsuda^,, Emmanuelle Jouanguy^*,, Dominique Gendrel^|| and Jean-Laurent Casanova^*,,¶

^* Laboratoire de Génétique Humaine des Maladies Infectieuses, Institut National de la Santé et de la Recherche Médicale, U550, Laboratoire du Développement du Système Immunitaire, U783, Université Paris René Descartes, Centre d’Étude des déficits immunitaires, ^¶ Unité d’Hématologie et d’Immunologie Pédiatriques, Hôpital Necker-Enfants Malades, and ^|| Pédiatrie Générale, Groupe Hospitalier Cochin-Saint Vincent de Paul, Paris, France

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by European Union Grant QLK2-CT-2002-00846 (to A.P.). J.-L.C. is an International Scholar of the Howard Hughes Medical Institute.

² Address correspondence and reprint requests to Dr. Anne Puel, Laboratoire de Génétique Humaine des Maladies Infectieuses, Institut National de la Santé et de la Recherche Médicale Unité 550, Université Paris René Descartes, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75015 Paris, France. E-mail address: puel{at}necker.fr

³ Abbreviations used in this paper: IRAK, IL-1R-associated kinase; CRP, C-reactive protein; PCT, procalcitonin; VZV, varicella-zoster virus; UTR, untranslated region.