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The pathogenesis and diagnosis of systemic lupus erythematosus: still not resolved

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Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations affecting different tissues. A characteristic feature of SLE is the presence of autoantibodies against double-stranded (ds)DNA, histones and nucleosomes, and other chromatin components. SLE is a prototype type III hypersensitivity reaction. Local deposition of anti-nuclear antibodies in complex with released chromatin induces serious inflammatory conditions by activation of the complement system. The severe renal manifestation, lupus nephritis, is classified based on histological findings in renal biopsies. Apoptotic debris, including chromatin, is present in the extracellular matrix and circulation of patients with SLE. This may be due to an aberrant process of apoptosis and/or insufficient clearance of apoptotic cells/chromatin. The non-cleared apoptotic debris may lead to activation of both the innate and adaptive immune systems. In addition, an aberrant presentation of peptides by antigen-presenting cells, disturbed selection processes for lymphocytes, and deregulated lymphocyte responses may be involved in the development of autoimmunity. In the present review, we briefly will summarize current knowledge on the pathogenesis of SLE. We will also critically discuss and challenge central issues that need to be addressed in order to fully understand the pathogenic mechanisms involved in the development of SLE and in order to have an improved diagnosis for SLE. Disappointingly, in our opinion, there are still more questions than answers for the pathogenesis, diagnosis, and treatment of SLE.

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Acknowledgments

Elmar Pieterse is acknowledged for the help in preparing Fig. 1. We thank Rod Wolstenholme (Faculty of Health Sciences, Uit) for expert help in preparing Fig. 2. This study was supported by Northern Norway Regional Health Authority Medical Research Program (Grant nos. SFP-100-04 and SFP-101-04), the University of Tromsø as Milieu (OPR), and the Dutch Arthritis Association (Grant 09-1-308; JvdV).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, 9037, Tromsø, Norway

    Ole Petter Rekvig

  2. Department of Nephrology (480), Radboud University Medical Centre, Geert Grooteplein 10, 6525 GA, Nijmegen, The Netherlands

    Johan Van der Vlag

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  1. Ole Petter Rekvig
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  2. Johan Van der Vlag
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Correspondence to Ole Petter Rekvig or Johan Van der Vlag.

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This article is a contribution to the special issue on B cell-mediated autoimmune diseases - Guest Editors: Thomas Winkler and Reinhard Voll

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Rekvig, O.P., Van der Vlag, J. The pathogenesis and diagnosis of systemic lupus erythematosus: still not resolved. Semin Immunopathol 36, 301–311 (2014). https://doi.org/10.1007/s00281-014-0428-6

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