Seminars in Immunopathology

, Volume 36, Issue 3, pp 301–311 | Cite as

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



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.


Systemic lupus erythematosus Lupus nephritis Chromatin Apoptosis NETs DNaseI Renal 



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).

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health SciencesUniversity of TromsøTromsøNorway
  2. 2.Department of Nephrology (480)Radboud University Medical CentreNijmegenThe Netherlands

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