Abstract
Background
The presence of circulating antinuclear antibodies (ANAs) is a hallmark of immune dysregulation in patients with systemic sclerosis (SSc).
Objective
A variety of ANAs are associated with unique sets of disease manifestations and are widely used in clinical practice in SSc. This study aimed to investigate the clinical features of SSc patients negative for ANAs in a Chinese Rheumatism Data Center (CRDC) multicenter cohort in China.
Methods
Patients were prospectively recruited between April 2008 and June 2019 from 154 clinical centers nationwide, and all cases fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Results for antinuclear antibodies were intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those negative for ANAs.
Results
Antinuclear antibodies were detected in 2129 of 2809 patients enrolled in the study; 4.2% of patients were negative. There were more males among ANA-negative SSc patients (29/60 vs. 294/1746, p < 0.001). The incidence of certain critical organ involvement, including gastroesophageal reflux (5.6% vs. 18.5%, p = 0.002), interstitial lung disease (65.2% vs. 77.9%, p = 0.015), and pulmonary arterial hypertension (11.5% vs. 29.0%, p = 0.006) was significantly lower in ANA-negative patients than in ANA-positive patients. The proportion of abnormal erythrocyte sedimentation rate (32.4% vs. 47.6%, p = 0.013) and IgG elevation (14.3% vs. 37.0%, p = 0.003), an indicator of disease activity, was significantly lower in ANA-negative patients than in ANA-positive patients.
Conclusion
Antinuclear antibodies are strongly associated with the clinical manifestations of systemic sclerosis, with ANA-negative SSc patients tending to exhibit relatively milder disease.
Zusammenfassung
Hintergrund
Das Vorhandensein von zirkulierenden antinukleären Antikörpern (ANA) ist ein Merkmal der Immundysregulation bei Patienten mit systemischer Sklerose (SSc).
Zielsetzung
Eine Vielzahl unterschiedlicher ANA wird mit einzigartigen Krankheitsmanifestationen in Verbindung gebracht und ist bei SSc in der klinischen Praxis weit verbreitet. Ziel dieser Studie war es, die klinischen Merkmale von SSc-Patienten zu untersuchen, die in einer multizentrischen Kohorte des Chinese Rheumatism Data Center (CRDC) in China negativ auf ANA reagieren.
Methoden
Die Patienten wurden zwischen April 2008 und Juni 2019 aus 154 klinischen Zentren im ganzen Land prospektiv rekrutiert, und alle Fälle erfüllten die ACR/EULAR-Klassifikationskriterien für systemische Sklerose von 2013. Die Ergebnisse für antinukleäre Antikörper wurden erfasst. Demografische, klinische und Labordaten von ANA-positiven und ANA-negativen Patienten wurden verglichen.
Ergebnisse
Antinukleäre Antikörper wurden bei 2129 von 2809 in die Studie aufgenommenen Patienten nachgewiesen; 4,2 % der Patienten waren negativ. Unter den ANA-negativen SSc-Patienten waren mehr Männer (29/60 vs. 294/1746; p < 0,001). Die Inzidenz bestimmter kritischer Organbeteiligungen, darunter gastroösophagealer Reflux (5,6 % vs. 18,5 %; p = 0,002), interstitielle Lungenerkrankung (65,2 % vs. 77,9 %, p = 0,015) und pulmonale arterielle Hypertonie (11,5 % vs. 29,0 %; p = 0,006), war bei ANA-negativen Patienten signifikant niedriger als bei ANA-positiven Patienten. Der Anteil der abnormalen Erythrozytensedimentationsrate (ESR; 32,4 % vs. 47,6 %; p = 0,013) und IgG-Erhöhung (14,3 % vs. 37,0 %, p = 0,003), ein Indikator für Krankheitsaktivität, war bei ANA-negativen Patienten signifikant niedriger als bei ANA-positiven Patienten.
Schlussfolgerung
Antinukleäre Antikörper stehen in engem Zusammenhang mit den klinischen Manifestationen der systemischen Sklerose, wobei ANA-negative SSc-Patienten in der Regel eine relativ mildere Erkrankung aufweisen.
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Acknowledgements
We thank the CRDC multicenter coauthors as above for assistance with case collections.
Funding
This study was supported by the CAMS Innovation Fund for Medical Sciences (CIFMS; 2019-I2M-2-008).
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M. Hui, X. Wang, J. Zhou, L. Zhang, X. Duan, M. Li, Q. Wang, J. Zhao, Y. Hou, D. Xu, and X. Zeng declare that they have no competing interests.
This study was approved by Chinese Rheumatism Data Center (CRDC) with the number S‑478. Informed consent was obtained.
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Ulf Müller-Ladner, Bad Nauheim
Uwe Lange, Bad Nauheim
Min Hui and Xianbin Wang contributed equally to this work.
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All data generated or analyzed during this study are included in the article.
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Hui, M., Wang, X., Zhou, J. et al. Systemic sclerosis patients with negative antinuclear antibodies have distinctive clinical manifestations: a multicenter CRDC cohort in China. Z Rheumatol 83 (Suppl 1), 160–166 (2024). https://doi.org/10.1007/s00393-022-01242-0
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DOI: https://doi.org/10.1007/s00393-022-01242-0