Glomerular immune deposits in murine lupus models may contain histones

Schmiedeke, Thomas; Stoeckl, F; Muller, Sylviane; Sugisaki, Yuichi; Batsford, Steven; Woitas, Rainer P.; Vogt, Arnold

doi:10.1111/j.1365-2249.1992.tb05867.x

Cited by 38 publications

(15 citation statements)

References 26 publications

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“…It has been described that serum AHA levels significantly decrease just before the appearance of glomerular injury and proteinuria, suggesting that AHA may bind to unsaturated epitopes of the autoantigen in target organs (2). Using rabbit Abs to H2A and H3 histone peptides and mAbs, immune deposits containing histones have been detected in both glomerular and epidermal basement membranes of lupus patients (3,4) as well as in the kidneys from NZB/W mice and mice with graft-versus-host disease (5). Furthermore, it was reported that patients with both initial anti-DNA Ab and AHA reactivity have a greater risk of developing proliferative glomerulonephritis (6).…”

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confidence: 96%

Identification of New Pathogenic Players in Lupus: Autoantibody-Secreting Cells Are Present in Nephritic Kidneys of (NZBxNZW)F1 Mice

Lacotte

Dumortier

Décossas

et al. 2010

The Journal of Immunology

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An important hallmark of systemic lupus erythematosus is the production of autoantibodies specific for nuclear Ags, among which nucleosomes and their constituents, DNA and histones. It is widely admitted that some of these autoantibodies contribute largely in lupus pathogenesis because of their nephritogenic potential. However, the underlying mechanisms are still debated. In this study, we analyzed the autoimmune response against histone H2B during the course of the disease in lupus-prone (NZBxNZW)F1 mice, both in lymphoid organs and kidneys, and we assessed its potential involvement in lupus pathogenicity. We found that the N-terminal region of histone H2B represents a preferential target for circulating autoantibodies, which kinetics of appearance positively correlates with disease development. Furthermore, immunization of preautoimmune (NZBxNZW)F1 mice with H2B peptide 1–25 accelerates the disease. Kidney eluates from diseased (NZBxNZW)F1 mice do contain IgG Abs reacting with this peptide, and this H2B sequence was found to be accessible to specific Ab probes in Ag-containing deposits detected in nephritic kidneys. Finally, compared with control normal mice and to young preautoimmune (NZBxNZW)F1 animals, the frequency of cells secreting autoantibodies reacting with peptide 1–25 was significantly raised in the spleen and bone marrow and most importantly on a pathophysiological point of view, locally, in nephritic kidneys of diseased (NZBxNZW)F1 mice. Altogether our results demonstrate the existence in (NZBxNZW)F1 mice of both a systemic and local B cell response targeting the N-terminal region of histone H2B, and highlight the potential implication of this nuclear domain in lupus pathology.

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confidence: 96%

Identification of New Pathogenic Players in Lupus: Autoantibody-Secreting Cells Are Present in Nephritic Kidneys of (NZBxNZW)F1 Mice

Lacotte

Dumortier

Décossas

et al. 2010

The Journal of Immunology

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“…Positive glomerular fluorescence was seen in 22/22 proteinuric and 3/5 non-proteinuric mice using rabbit antibodies to histone peptides 1 21 of H3 and 1 9 of H2A (not shown; see [11]}. Deposits of histones were always accompanied by autologous IgG and C3.…”

Section: Immunoftuorescence Studies On Kidney Sectionsmentioning

confidence: 99%

“…Deposits of histones were always accompanied by autologous IgG and C3. No significant reaction was seen using antibodies to ubiquitin and peptide T4 [11]. A number of rabbit antisera to other histone peptides gave a negative reaction [11].…”

Section: Immunoftuorescence Studies On Kidney Sectionsmentioning

confidence: 99%

“…several aminoaeyl-tRNA synthetases and the nucleolar antigen NOR9() have also been reported [9,10], Using rabbit antibodies to histone peptides. we demonstrated previously [11] that histones. and in particular the Nlerminal regions of histones H3 and H2A, were exposed in glomerular deposits of GVHD mice.…”

Section: Introductionmentioning

confidence: 99%

“…When this threshold value was used, none of the sera from normal BALB/c mice was found positive (Table I) hmnunoblotting and immunofluorescence studies Western blot analysis of mouse sera was performed as described previously [18]. Immunofiuoreseence studies to detect glomerular deposition of histones and ubiquitin were tbe subjeet of a prior publication [11].…”

Section: Mice and Induction Of Graft-versus-ho'it Diseasementioning

confidence: 99%

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Antibodies to DNA, chromatin core particles and histones in mice with graft-versus-host disease and their involvement in glomerular injury

Mézière

Stockl

Batsford

et al. 1994

Clinical and Experimental Immunology

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SUMMARYChronic grafl-vcnwA-host disease (GVHD) was induced in female (C57 B10S/DBA/2)F| hybrid mice with two successive injections of lymphoid cells from parental DBA/2 strain. Serial bleedings of 27 GVHD mice were screened with a panel of antigens including the five histones HI, H2A, H2B, H3 and H4, 15 histonc peptides. core particles. dsDNA. heat-shoek proteins hsp70 and ubiquitin, a branched peptide of ubiquitinaled H2A (U-H2A), poly(ADP-ribose) and SSB/l,a protein. The predominant IgG response to histone peptides was directed against regions 204-218 of HI, 1-25 of H2B and 1 29 of H4. GVHD mice also produced IgG antibodies lo dsDNA and chromatin core particles as reported previously. IgG antibodies reacting with dsDNA appeared before antibodies to core particles and histones. Raised levels ofantibodies to U'H2A. but not to monomeric ubiquitin. were also found. While the level ofantibodies to dsDNA. histones and core particles decreased significantly before ihe appearance of proteinuria, suggesting their involvement in glomerular injury, the longitudinal pattern of anti-U-H2A peptide response was apparently not linked to the manifestation of lupus nephritis in GVHD mice.

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Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis

Grootscholten¹,

Bruggen²,

Pijl

et al. 2003

Arthritis & Rheumatism

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Objective. Antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulfate (HS) in the glomerular basement membrane. This binding is due to the binding of the positively charged histones to the strongly anionic HS. Nucleosomes and histones have been identified in glomerular deposits in human lupus nephritis. We investigated whether nucleosomes are present in the basement membrane of nonlesional skin of lupus patients.Methods. Skin biopsy samples from patients with systemic lupus erythematosus (SLE) (30 with active lupus nephritis and 15 with inactive disease) and controls (with parapemphigus or diabetes) were stained for IgG, histones, DNA, and nucleosomes.Results. IgG deposits were found in 87% of the patients with lupus nephritis, in 33% of the patients with inactive disease, and in 71% of the parapemphigus patients. Using polyclonal antihistone antibodies, histones were detected in 87% of lupus nephritis patients, but in none of the other SLE patients or the diabetes controls (P < 0.0001). Among the parapemphigus controls, 14% of samples stained positive in one of the polyclonal antihistone stainings (P < 0.0001). Using monoclonal antibodies, histones and DNA were identified in 21% of the lupus nephritis patients. Although none of the other groups showed positive staining for nucleosomes, 7% of the lupus nephritis biopsy samples were positive using antinucleosome monoclonal antibodies. Colocalization of nucleosomal antigens and IgG was confirmed using confocal laser microscopy.Conclusion. These findings suggest that nucleosome-mediated binding of autoantibodies to basement membranes may also occur at sites in the body other than in the glomerulus.

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Glomerular immune deposits in murine lupus models may contain histones

Cited by 38 publications

References 26 publications

Identification of New Pathogenic Players in Lupus: Autoantibody-Secreting Cells Are Present in Nephritic Kidneys of (NZBxNZW)F1 Mice

Identification of New Pathogenic Players in Lupus: Autoantibody-Secreting Cells Are Present in Nephritic Kidneys of (NZBxNZW)F1 Mice

Antibodies to DNA, chromatin core particles and histones in mice with graft-versus-host disease and their involvement in glomerular injury

Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis

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