Antihistone and anti–double-stranded deoxyribonucleic acid antibodies are associated with renal disease in systemic lupus erythematosus

Cortés-Hernández, Josefina; Ordi‐Ros, Josep; Labrador, M; Buján, Segundo; Balada, Eva; Segarra, Alfons; Vilardell‐Tarrés, Miquel

doi:10.1016/j.amjmed.2003.08.034

Cited by 84 publications

(73 citation statements)

References 31 publications

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“…The anti-dsDNA autoantibodies have been strongly associated with immune complex disease, and are thought to contribute to renal inflammation and deterioration in patients with lupus nephritis (15)(16)(17)(18)(19). In addition to dsDNA, a number of specific epitopes within the nucleus have been shown to give rise to a positive test in SLE patients.…”

Section: S Ystemic Sclerosis (Ssc)mentioning

confidence: 99%

Demonstration of Autoimmunity in the Tight Skin-2 Mouse: A Model for Scleroderma

Gentiletti

McCloskey

Artlett

et al. 2005

The Journal of Immunology

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The tight skin-2 (Tsk2/+) mouse has been proposed as an animal model of systemic sclerosis (SSc) because this animal exhibits increased collagen synthesis and accumulation in the dermis. The Tsk2/+ mouse also has been reported to have a mononuclear cell infiltrate in the dermis; however, to date no evidence of autoimmunity has been described in this animal model. We report here that Tsk2/+ mice harbor numerous autoantibodies in their plasma including some, which are similar to those, present in SSc patients. Immunofluorescence with HEp-2 cells revealed the presence of anti-nuclear Abs (ANAs) in the plasma of 92% of the Tsk2/+ mice. In contrast, <5% of cage-mated CAST/ei mice had a positive ANA and none of the C3H/HeJ age-matched controls were positive. Homogenous, speckled, rim, nucleolar, centromere as well as combinations of these patterns were observed. The proportion of Tsk2/+ animals with a positive ANA increased slightly with age. ELISAs showed that 93% of the Tsk2/+ animals were positive for anti-Scl70, 82% for anti-centromere, 5% for anti-RNP/Sm, and none were positive for anti-RNA-polymerase II Abs. Indirect immunofluorescence with Crithidia luciliae and ELISA for anti-dsDNA Abs showed that 76% of Tsk2/+ mice were positive for this autoantibody. The high frequency of anti-Scl70 and anti-centromere autoantibodies indicates that Tsk2/+ mice display some humoral immune alterations which are similar to those found in patients with SSc. However, the Tsk2/+ mice also develop autoantibodies to dsDNA and a majority of the mice develop multiple autoantibody specificities (anti-Scl70, anti-CENP-B, and anti-dsDNA) indicating that the mouse may be a useful model to study autoimmunity in a wider spectrum of connective tissue diseases.

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Section: S Ystemic Sclerosis (Ssc)mentioning

confidence: 99%

Demonstration of Autoimmunity in the Tight Skin-2 Mouse: A Model for Scleroderma

Gentiletti

McCloskey

Artlett

et al. 2005

The Journal of Immunology

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“…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).…”

mentioning

confidence: 98%

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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“…The characteristics of the current study population were compared with those of other major surveys from other regions in the Middle East, Europe, and North America [14,[18][19][20][21]. The overall prevalence rate of lupus nephritis was higher in the current study compared to notable surveys [22,23].…”

Section: Discussion ___________________________mentioning

confidence: 99%

Clinical picture of lupus nephritis in patients with systemic lupus erythematosus (SLE): Results of a large survey

et al. 2017

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Systemic lupus erythematosus (SLE) is a chronic multisystem disorder. Lupus nephritis (LN) is a common serious complication of SLE. LN needs prolonged care and complex therapeutic modalities. This study assessed the characteristics of Persian SLE patients with LN (LN subgroup) and an SLE subpopulation without LN (non-LN subgroup). Furthermore, the association of LN with extrarenal manifestations of SLE was studied. This study assessed 2355 SLE patients from the electronic database of the Rheumatology Research Center (RRC), Tehran University of Medical Sciences (TUMS). The clinical and laboratory data of enrolled patients was retrieved. The chi-square test was used to compare extrarenal manifestations of the LN and non-LN subgroups. Odds ratios (OR) were used to present the strength of associations. The LN subgroup included 1604 cases (68.1%) with a mean age at SLE onset of 24.612.5 years and a female-to-male ratio of 8.7/1. Class IV nephritis was the most common type of LN (53.1%). The comparison of extrarenal manifestations revealed statistically significant differences between LN and non-LN subgroups. Major organ involvement including cardiopulmonary, hematologic, musculoskeletal and neuropsychiatric features was significantly more common in LN patients. On the contrary, discoid rash was significantly more common in the non-LN subgroup. This study revealed that LN is positively associated with musculoskeletal, mucocutaneous, and neuropsychiatric features of SLE.

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Antihistone and anti–double-stranded deoxyribonucleic acid antibodies are associated with renal disease in systemic lupus erythematosus

Cited by 84 publications

References 31 publications

Demonstration of Autoimmunity in the Tight Skin-2 Mouse: A Model for Scleroderma

Demonstration of Autoimmunity in the Tight Skin-2 Mouse: A Model for Scleroderma

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

Clinical picture of lupus nephritis in patients with systemic lupus erythematosus (SLE): Results of a large survey

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