Circulating chromatin-anti-chromatin antibody complexes bind with high affinity to dermo-epidermal structures in murine and human lupus nephritis.
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.
Fismen
S
S
Department of Pathology, University Hospital of Northern Norway, N-9038 Tromsø, Norway.
Hedberg
A
A
Fenton
K A
KA
Jacobsen
S
S
Krarup
E
E
Kamper
A L
AL
Rekvig
O P
OP
Mortensen
E S
ES
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D000936:Antigen-Antibody Complex / Q000097:blood*; D001706:Biopsy; D002196:Capillaries / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002843:Chromatin / Q000276:immunology* / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism; D000097794:Kalinin
D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D015815:Cell Adhesion Molecules; D002843:Chromatin; D024042:Collagen Type I; D024141:Collagen Type IV; D006657:Histones; D007074:Immunoglobulin G; D014157:Transcription Factors; D000097794:Kalinin