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Circulating chromatin–anti-chromatin antibody complexes bind with high affinity to dermo-epidermal structures in murine and human lupus nephritis

Department of Pathology, University Hospital of Northern Norway, N-9038 Tromsø, Norway; Department of Pathology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, N-9037 Tromsø, Norway

A Hedberg

Departments of Biochemistry, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, N-9037 Tromsø, Norway

KA Fenton

Departments of Biochemistry, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, N-9037 Tromsø, Norway

S Jacobsen

Department of Rheumatology, Copenhagen University Hospital Rigshospitalet, Denmark

E Krarup

Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Denmark

AL Kamper

Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Denmark

OP Rekvig

Departments of Biochemistry, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, N-9037 Tromsø, Norway; Department of Rheumatology, University Hospital of Northern Norway, N-9038 Tromsø, Norway

ES Mortensen

Department of Pathology, University Hospital of Northern Norway, N-9038 Tromsø, Norway; Department of Pathology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, N-9037 Tromsø, Norwayelin.mortensen{at}unn.no

Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo-epidermal immune complex deposits have similar molecular composition as glomerular deposits, (ii) whether chromatin fragments bind dermo-epidermal structures, and (iii) whether deposits in nephritic glomeruli predispose for accumulation of similar deposits in skin. Paired skin and kidney biopsies from nephritic (NZBxNZW)F1 and MRL-lpr/lpr mice and from five patients with lupus nephritis were analysed by immunofluorescence, immune electron microscopy (IEM) and co-localization TUNEL IEM. Affinity of chromatin fragments for membrane structures was determined by surface plasmon resonance. Results demonstrated (i) presence of EDS containing chromatin fragments and IgG in both organs in nephritic patients, (ii) chromatin fragments possessed high affinity for dermo-epidermal laminins and collagens, (iii) glomerular immune complex deposits did not predict similar interstitial deposits in skin, although such complexes were present in capillary lumina in glomeruli and skin of all nephritic individuals. Thus, chromatin-IgG complexes accounting for lupus nephritis seem to reach skin through circulation, but other undetermined factors are required for these complexes to deposit within skin membranes.

Key Words: chromatin • dermatitis • IgG anti-dsDNA antibodies • nephritis • systemic lupus nephritis

Lupus, Vol. 18, No. 7, 597-607 (2009)
DOI: 10.1177/0961203308100512


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