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

Abstract

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.

C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis

“…We find it plausible to interpret the tissue co-localization of IgG, C1q and CRP as ICs containing [49]. Indeed, also nucleosomes/chromatin is a well-recognized constituent in ICs from LN patients [50].…”

Lupus Nephritis: Enigmas, Conflicting Models and an Emerging Concept

“…This result explains the systemic character of tissue damage in SLE. Comparative studies of components of immune complexes and their localization in skin and glomerulus membranes and matrices demonstrated that they have similar structure (99,100). However, deposition of immune complexes in glomeruli did not predict deposition in skin.…”

Circulating levels of chromatin fragments are inversely correlated with anti-dsDNA antibody levels in human and murine systemic lupus erythematosus

“…These autoantibodies form complexes with nucleosomes that deposit within the kidney and the skin [2], and the affection of the kidney causes a most serious and potentially fatal complication in human SLE; lupus nephritis [3]. Other nuclear autoantibodies like anti-nucleosome, anti-nucleolin and anti-centromere protein antibodies has been implicated in the development of lupus nephritis [4][5][6].…”