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Research ArticleAccepted Article

Association between centromere and topoisomerase specific immune responses and the degree of microangiopathy in Systemic Sclerosis

Nina M. van Leeuwen, Corrie M. Wortel, Cynthia M. Fehres, Jaap. A Bakker, Hans. U. Scherer, René E.M Toes, Tom W.J Huizinga and Jeska K. de Vries-Bouwstra
The Journal of Rheumatology June 2020, jrheum.191331; DOI: https://doi.org/10.3899/jrheum.191331
Nina M. van Leeuwen
From the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands. Address correspondence to Nina M. van Leeuwen, department of Rheumatology Leiden University Medical Center, C1-R, PO Box 9600, 2300 RC, Leiden, the Netherlands. E-mail: n.m.van_leeuwen@lumc.nl
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Corrie M. Wortel
From the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands. Address correspondence to Nina M. van Leeuwen, department of Rheumatology Leiden University Medical Center, C1-R, PO Box 9600, 2300 RC, Leiden, the Netherlands. E-mail: n.m.van_leeuwen@lumc.nl
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Cynthia M. Fehres
From the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands. Address correspondence to Nina M. van Leeuwen, department of Rheumatology Leiden University Medical Center, C1-R, PO Box 9600, 2300 RC, Leiden, the Netherlands. E-mail: n.m.van_leeuwen@lumc.nl
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Jaap. A Bakker
From the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands. Address correspondence to Nina M. van Leeuwen, department of Rheumatology Leiden University Medical Center, C1-R, PO Box 9600, 2300 RC, Leiden, the Netherlands. E-mail: n.m.van_leeuwen@lumc.nl
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Hans. U. Scherer
From the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands. Address correspondence to Nina M. van Leeuwen, department of Rheumatology Leiden University Medical Center, C1-R, PO Box 9600, 2300 RC, Leiden, the Netherlands. E-mail: n.m.van_leeuwen@lumc.nl
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René E.M Toes
From the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands. Address correspondence to Nina M. van Leeuwen, department of Rheumatology Leiden University Medical Center, C1-R, PO Box 9600, 2300 RC, Leiden, the Netherlands. E-mail: n.m.van_leeuwen@lumc.nl
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Tom W.J Huizinga
From the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands. Address correspondence to Nina M. van Leeuwen, department of Rheumatology Leiden University Medical Center, C1-R, PO Box 9600, 2300 RC, Leiden, the Netherlands. E-mail: n.m.van_leeuwen@lumc.nl
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Jeska K. de Vries-Bouwstra
From the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands. Address correspondence to Nina M. van Leeuwen, department of Rheumatology Leiden University Medical Center, C1-R, PO Box 9600, 2300 RC, Leiden, the Netherlands. E-mail: n.m.van_leeuwen@lumc.nl
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Abstract

Objective Autoreactive antibody responses, including the use of several isotypes of autoantibodies, have been shown to associate with clinical outcome in several rheumatic autoimmune diseases. The goal of this study was 1) to evaluate whether anti-centromere antibody(ACA) and anti-topoisomerase antibody(ATA) specific isotype expression and 2) organ involvement associate with the degree of microangiopathy in SSc.

Methods ACA and ATA IgG, IgM and IgA levels were measured in baseline serum samples of ACA IgG+ and ATA IgG+ SSc patients. The degree of microangiopathy was determined based on nailfold videocapillaroscopy images at the same time point. Logistic regression analyses with autoantibodies, clinical characteristics, isotype expression and ACA resp. ATA IgG, IgM and IgA levels as independent and NVC pattern as dependent variable were performed.

Results In 164 patients isotype levels and degree of microangiopathy were evaluated. Logistic regression confirmed the association of the degree of microangiopathy with the presence of digital ulcers(OR 3.1 (1.4-6.6)), interstitial lung disease(OR 3.2 (1.1-9.7)) and pulmonary arterial hypertension(OR 5.25 (1.69-16.36)). ATA positivity was associated with more severe microangiopathy(OR 2.09 (1.05-4.13)). Patients that solely expressed ACA IgG showed a trend towards less severe microangiopathy compared to patients expressing also ACA IgM and/or IgA, levels of ACA IgG and ATA IgM associated with microangiopathy severity.

Conclusion We observed an association between ACA and ATA responses and the degree of microangiopathy in SSc. These findings might indicate that the breath of the autoimmune response as reflected by autoantibody production and microvascular damage interact in the pathophysiology of SSc.

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The Journal of Rheumatology
Vol. 50, Issue 3
1 Mar 2023
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Accepted manuscript
Association between centromere and topoisomerase specific immune responses and the degree of microangiopathy in Systemic Sclerosis
Nina M. van Leeuwen, Corrie M. Wortel, Cynthia M. Fehres, Jaap. A Bakker, Hans. U. Scherer, René E.M Toes, Tom W.J Huizinga, Jeska K. de Vries-Bouwstra
The Journal of Rheumatology Jun 2020, jrheum.191331; DOI: 10.3899/jrheum.191331

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Accepted manuscript
Association between centromere and topoisomerase specific immune responses and the degree of microangiopathy in Systemic Sclerosis
Nina M. van Leeuwen, Corrie M. Wortel, Cynthia M. Fehres, Jaap. A Bakker, Hans. U. Scherer, René E.M Toes, Tom W.J Huizinga, Jeska K. de Vries-Bouwstra
The Journal of Rheumatology Jun 2020, jrheum.191331; DOI: 10.3899/jrheum.191331
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