Abstract | OBJECTIVE: METHODS: Serum samples obtained from 2 independent prospective SSc cohorts (n = 326), patients with idiopathic PAH (n = 12), and healthy control subjects (n = 100) were analyzed for CCL19/CCL21 levels, by enzyme-linked immunosorbent assay. The levels were defined as either high or low, using the mean + 2 SD value in controls as the cutoff value. Risk stratification at the time of PAH diagnosis and PAH-related events were performed. Descriptive and Cox regression analyses were conducted. RESULTS: CCL21 levels were higher in patients with SSc compared with controls and were elevated prior to the diagnosis of PAH. PAH was more frequent in patients with high CCL21 levels (≥0.4 ng/ml) than in those with low CCL21 levels (33.3% versus 5.3% [P < 0.001]). In multivariate analyses, CCL21 was associated with PAH (hazard ratio [HR] 5.1, 95% CI 2.39-10.76 [P < 0.001]) and occurrence of PAH-related events (HR 4.7, 95% CI 2.12-10.46, P < 0.001). Risk stratification at the time of PAH diagnosis alone did not predict PAH-related events. However, when risk at diagnosis was combined with high or low CCL21 level, there was a significant predictive effect (HR 1.3, 95% CI 1.03-1.60 [P = 0.027]). A high CCL21 level was associated with decreased survival (P < 0.001). CONCLUSION: CCL21 appears to be a promising marker for predicting the risk of SSc-related PAH and PAH progression. CCL21 may be part of a dysregulated immune pathway linked to the development of lung vascular damage in SSc.
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Authors | Anna-Maria Hoffmann-Vold, Roger Hesselstrand, Håvard Fretheim, Thor Ueland, Arne K Andreassen, Cathrine Brunborg, Vyacheslav Palchevskiy, Øyvind Midtvedt, Torhild Garen, Pål Aukrust, John A Belperio, Øyvind Molberg |
Journal | Arthritis & rheumatology (Hoboken, N.J.)
(Arthritis Rheumatol)
Vol. 70
Issue 10
Pg. 1644-1653
(10 2018)
ISSN: 2326-5205 [Electronic] United States |
PMID | 29687634
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2018, American College of Rheumatology. |
Chemical References |
- Biomarkers
- CCL21 protein, human
- Chemokine CCL21
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Topics |
- Adult
- Aged
- Biomarkers
(blood)
- Chemokine CCL21
(blood)
- Enzyme-Linked Immunosorbent Assay
- Familial Primary Pulmonary Hypertension
(blood, etiology)
- Female
- Humans
- Male
- Middle Aged
- Proportional Hazards Models
- Prospective Studies
- Reference Values
- Risk Assessment
(methods)
- Risk Factors
- Scleroderma, Systemic
(blood, complications)
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