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Does Circulating IL-17 Identify a Subset of Patients With Idiopathic Pulmonary Arterial Hypertension?IL-17 in Pulmonary Arterial Hypertension FREE TO VIEW

Lars Harbaum, MD; Tim Oqueka, MD; Antonia Glatzel, MSc; Jan K. Hennigs, MD; Nicole Lüneburg, PhD; Hans Klose, MD
Author and Funding Information

From the Center for Pulmonary Hypertension (Drs Harbaum, Oqueka, and Klose), II. Department of Medicine (Drs Harbaum, Oqueka, Hennigs, and Klose), and Institute of Clinical Pharmacology and Toxicology (Ms Glatzel and Dr Lüneburg) University Medical Center Hamburg-Eppendorf; and Wall Center for Pulmonary Vascular Disease and Cardiovascular Institute (Dr Hennigs), Stanford University School of Medicine, Stanford, CA.

CORRESPONDENCE TO: Lars Harbaum, MD, Section Pneumology, II. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; e-mail: l.harbaum@uke.de


CONFLICT OF INTEREST: None declared.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(4):e131-e132. doi:10.1378/chest.15-0963
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Published online
To the Editor:

We read with great interest the article in CHEST (June 2015) by Hautefort et al,1 who demonstrated activity of the T helper 17 pathway in patients with idiopathic pulmonary arterial hypertension (IPAH). The authors further substantiated a potential role of an autoimmune pathogenesis in IPAH, a disease defined by the absence of known causes or associated conditions. “A flavor of autoimmunity” in IPAH, as discussed by the authors,1 also arises from studies showing a high prevalence of auto-antibodies in patients with IPAH and their role in in vitro models.1,2

IL-17A can be detected in the circulation of patients with cardiovascular diseases. However, in that population, concerns regarding the pathogenic influence of IL-17A are raised by Simon et al,3 who showed, albeit inconsistently with the assumed deleterious role for IL-17A in atherosclerosis, a favorable outcome for patients with acute myocardial infarction and high levels of circulating IL-17A.4

We hypothesized that circulating IL-17A levels are also altered in a subset of patients with IPAH. Thirty-two patients with IPAH, diagnosed according to current recommendations,5 and seven age- and sex-matched healthy subjects were prospectively recruited between 2011 and 2012 at the University Medical Center Hamburg-Eppendorf, Germany. Six-minute walking distances (6MWDs), World Health Organization functional class, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, and echocardiographic assessment were obtained on the day of sample collection. Serum samples were stored at −80°C and thawed only for measurement of IL-17A concentration using an enzyme-linked immunosorbent assay with a sensitivity threshold of 2 ng/L (Biosource Europe SA).

Elevated levels of IL-17A (> 2 ng/L) were found in five of 32 patients with IPAH (16%), with a mean level of 7.44 ± 5.56 ng/L. In comparison, two healthy subjects also showed detectable IL-17A levels of 6.4 and 9.4 ng/L, respectively. Characteristics of patients related to elevated IL-17A levels are given in Table 1. No significant correlation with clinical disease severity marker, such as 6MWDs or NT-proBNP, time to clinical worsening, or 2-year overall survival, was detected. Merely, the association with tricuspid annular plane systolic excursions raised the question about a protective role for IL-17A in cardiovascular diseases.

Table Graphic Jump Location
TABLE 1 ]  Characteristics of Patients With Idiopathic Pulmonary Arterial Hypertension Regarding Circulating IL-17A Levels

Data are presented as mean ± SD unless otherwise indicated. 6MWD = 6-min walking distance; ERA = endothelin-receptor antagonist; mPAP = mean pulmonary arterial pressure; NT-proBNP = N-terminal prohormone of brain natriuretic peptide; PDE5-I = phosphodiesterase-5 inhibitor; PVR = pulmonary vascular resistance; RAP = right atrial pressure; RVSP = right ventricular systolic pressure; TAPSE = tricuspid annular plane systolic excursion; WHO-FC = World Health Organization functional class.

a 

P values are calculated by Student t test unless otherwise indicated.

b 

χ2 test.

c 

Mann-Whitney U test.

Elevated IL-17A levels are, indeed, detectable in a minor subset of patients with IPAH, but likewise in some healthy subjects. We did not observe associations of IL-17A with disease severity or outcome. Our data support the findings by Hautefort et al1 and warrant the need for larger studies to disclose a more moderate implication of detectable IL-17A level in patients with IPAH.

References

Hautefort A, Girerd B, Montani D, et al. T-helper 17 cell polarization in pulmonary arterial hypertension. Chest. 2015;147(6):1610-1620. [CrossRef] [PubMed]
 
Terrier B, Tamby MC, Camoin L, et al. Identification of target antigens of antifibroblast antibodies in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2008;177(10):1128-1134. [CrossRef] [PubMed]
 
Simon T, Taleb S, Danchin N, et al. Circulating levels of interleukin-17 and cardiovascular outcomes in patients with acute myocardial infarction. Eur Heart J. 2013;34(8):570-577. [CrossRef] [PubMed]
 
Taleb S, Tedgui A, Mallat Z. IL-17 and Th17 cells in atherosclerosis: subtle and contextual roles. Arterioscler Thromb Vasc Biol. 2015;35(2):258-264. [CrossRef] [PubMed]
 
Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(suppl 25):D42-D50. [CrossRef] [PubMed]
 

Figures

Tables

Table Graphic Jump Location
TABLE 1 ]  Characteristics of Patients With Idiopathic Pulmonary Arterial Hypertension Regarding Circulating IL-17A Levels

Data are presented as mean ± SD unless otherwise indicated. 6MWD = 6-min walking distance; ERA = endothelin-receptor antagonist; mPAP = mean pulmonary arterial pressure; NT-proBNP = N-terminal prohormone of brain natriuretic peptide; PDE5-I = phosphodiesterase-5 inhibitor; PVR = pulmonary vascular resistance; RAP = right atrial pressure; RVSP = right ventricular systolic pressure; TAPSE = tricuspid annular plane systolic excursion; WHO-FC = World Health Organization functional class.

a 

P values are calculated by Student t test unless otherwise indicated.

b 

χ2 test.

c 

Mann-Whitney U test.

References

Hautefort A, Girerd B, Montani D, et al. T-helper 17 cell polarization in pulmonary arterial hypertension. Chest. 2015;147(6):1610-1620. [CrossRef] [PubMed]
 
Terrier B, Tamby MC, Camoin L, et al. Identification of target antigens of antifibroblast antibodies in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2008;177(10):1128-1134. [CrossRef] [PubMed]
 
Simon T, Taleb S, Danchin N, et al. Circulating levels of interleukin-17 and cardiovascular outcomes in patients with acute myocardial infarction. Eur Heart J. 2013;34(8):570-577. [CrossRef] [PubMed]
 
Taleb S, Tedgui A, Mallat Z. IL-17 and Th17 cells in atherosclerosis: subtle and contextual roles. Arterioscler Thromb Vasc Biol. 2015;35(2):258-264. [CrossRef] [PubMed]
 
Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(suppl 25):D42-D50. [CrossRef] [PubMed]
 
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