The association of antinuclear antibodies with organ involvement and survival in systemic sclerosis

Hesselstrand, Roger; Scheja, Agneta; Shen, Guoqiu; Wiik, A; Åkesson, Anita

doi:10.1093/rheumatology/keg170

Cited by 152 publications

(121 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Further testing by ELISA demonstrated that almost all homogenous, homogeneous/ rim, rim and centromere patterns were positive for both antidsDNA and anti-Scl70 autoantibodies (Table I). Almost all of the Tsk2/ϩ plasma samples with the speckled pattern were positive for Scl70 which correlates with what has been observed in SSc (7,22,26).…”

Section: Discussionsupporting

confidence: 84%

“…For example, patients with diffuse SSc tend to have Abs against topoisomerase I, RNA-polymerases, or U3 RNPs including fibrillarin (3,4,7,22). Anti-topoisomerase I Abs are the most frequently observed autoantibodies in these patients and are associated with pulmonary fibrosis and cardiac involvement (3,4,7,(22)(23)(24)(25)(26). Anti-RNA-polymerase Abs are associated with severe skin involvement and renal crisis (3,4,7,22,27).…”

Section: S Ystemic Sclerosis (Ssc)mentioning

confidence: 99%

See 1 more Smart Citation

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

Gentiletti

McCloskey

Artlett

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 84%

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

View full text Add to dashboard Cite

show abstract

“…This is consistent with the recognition that a significant number of patients with lcSSc have anti-topo I autoantibodies. Nevertheless, both of these antibodies have previously been reported to identify cases associated with poor outcome and renal or lung involvement (20,21). …”

Section: Discussionmentioning

confidence: 99%

Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: Application of a latent linear trajectory model

Shand

Lunt

Nihtyanova

et al. 2007

Arthritis & Rheumatism

170

111

View full text Add to dashboard Cite

Objective. To explore the relationship between changes in the severity of skin disease and morbidity and mortality in patients with diffuse cutaneous systemic sclerosis (dcSSc).Methods. From a large single-center cohort, we identified 225 patients with dcSSc for whom serial clinical information was available from within 24 months of the onset of the first non-Raynaud's phenomenon manifestation of SSc. The end points analyzed included death and heart, lung, kidney, and gastrointestinal tract involvement. Latent linear trajectory modeling (LTM) was applied to identify patients with a similar trajectory of modified Rodnan skin thickness score (MRSS) changes over the first 3 years of followup. Clinical outcomes were compared between 3 different LTM subgroups.Results. LTM permitted classification of 131 patients (58%) into 1 of 3 subgroups with different skin score trajectories. Survival was lowest in the subgroup of patients who had a high baseline skin score and experienced little improvement during followup (P ‫؍‬ 0.003). However, the frequency of clinical end points was similar in the subgroup with the most favorable trajectory (i.e., a low initial MRSS and subsequent improvement) and the subgroup with a high baseline MRSS and no improvement. Interestingly, the end point frequency was greatest in the subgroup with a high initial MRSS and subsequent improvement, suggesting that sustained severe skin disease does not necessarily predict the number of visceral complications, and that the relationship between the skin score and internal organ involvement in dcSSc is more complex than previously thought.Conclusion. Although mortality was highest among patients with the worst skin-related outcomes, no simple relationship between burden of disease and change in skin score was observed.

show abstract

“…They are present in up to 90% of SSc patient sera and are generally associated with specific SSc subtypes (35)(36)(37). However, their role in the pathogenesis of SSc is still unclear, and few studies have directly addressed this subject (for review, see ref.…”

Section: Discussionmentioning

confidence: 99%

DNA topoisomerase I binding to fibroblasts induces monocyte adhesion and activation in the presence of anti–topoisomerase I autoantibodies from systemic sclerosis patients

Hénault¹,

Robitaille²,

Senécal³

et al. 2006

Arthritis & Rheumatism

109

View full text Add to dashboard Cite

Objective. Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis due to excessive and dysregulated collagen production by fibroblasts. Previously, we reported that anti-DNA topoisomerase I (anti-topo I) antibodies bound specifically to fibroblast surfaces; however, we had not identified their antigenic target. We undertook this study to characterize the target of anti-topo I antibodies on fibroblasts and the effects of their binding.Methods. Purified topo I or topo I released from apoptotic cells was tested for surface binding to a number of human cell types by cell-based enzyme-linked immunosorbent assay, flow cytometry, and indirect immunofluorescence. Antibodies purified from SSc patient and normal control sera were used to detect topo I binding. The consequences of topo I and anti-topo I binding to fibroblasts were assessed by coculture with THP-1 monocytes.Results. The autoantigen topo I itself was found to bind specifically to fibroblasts in a dose-dependent and saturable manner, where it was recognized by anti-topo I from SSc patients. The binding of anti-topo I subsequently stimulated adhesion and activation of cocultured monocytes. Topo I released from apoptotic endothelial cells was also found to bind specifically to fibroblasts.Conclusion. The findings of this study thus confirm and extend the findings of our previous study by showing that topo I binding to fibroblast surfaces is both necessary and sufficient for anti-topo I binding. Second, topo I-anti-topo I complex binding can then trigger the adhesion and activation of monocytes, thus providing a plausible model for the amplification of the fibrogenic cascade in anti-topo I-positive SSc patients.

show abstract

The association of antinuclear antibodies with organ involvement and survival in systemic sclerosis

Abstract: AHA and a nucleolar HEp-2 cell pattern may indicate critical organ involvement and predict a reduced survival in SSc patients.

Cited by 152 publications

References 27 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

Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: Application of a latent linear trajectory model

DNA topoisomerase I binding to fibroblasts induces monocyte adhesion and activation in the presence of anti–topoisomerase I autoantibodies from systemic sclerosis patients

Contact Info

Product

Resources

About