Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by the production of autoantibodies, formation of immune complexes (IC), and activation of complement that ultimately fuel acute and/or chronic inflammation. Accumulation in blood and tissues of post-apoptotic remnants is considered of etiological and pathological importance for patients with SLE. Besides receptors directly recognizing apoptotic cells, soluble opsonins of the innate immune system bind apoptotic material dependent on the stage of apoptosis. We describe the binding to the surface of secondary necrotic cells (SNEC) of the serum opsonin CRP and further opsonins. We show that anti-dsDNA and anti-CRP autoantibodies bind and sensitize SNEC. Autoantibody-sensitized SNEC were cleared by macrophages in vitro and induced a pro-inflammatory cytokine response. In conclusion, anti-CRP, CRP, and SNEC form a ternary pyrogen endowed with strong pro-inflammatory capabilities which is able to maintain and perpetuate chronic inflammation.
Keywords: immune complexes, opsonins, CRP, anti-dsDNA, inflammation, SLE
Citation: Janko C, Franz S, Munoz LE, Siebig S, Winkler S, Schett G, Lauber K, Sheriff A, van der Vlag J and Herrmann M (2011) CRP/anti-CRP antibodies assembly on the surfaces of cell remnants switches their phagocytic clearance toward inflammation. Front. Immun. 2:70. doi: 10.3389/fimmu.2011.00070
Received: 15 August 2011;
Paper pending published: 05 October 2011;
Accepted: 14 November 2011; Published online: 02 December 2011.
Edited by:Amiram Ariel, University of Haifa, Israel
Reviewed by:Silvano Sozzani, University of Brescia, Italy
Copyright: © 2011 Janko, Franz, Munoz, Siebig, Winkler, Schett, Lauber, Sheriff, van der Vlag and Herrmann. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Sandra Franz, Department for Dermatology, Venerology and Allergology, Max Bürger Research Centre, University Leipzig, Johannisallee 30, 04103 Leipzig, Germany. e-mail: email@example.com
†Christina Janko Sandra Franz and Luis E. Munoz have contributed equally to this work.