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. 2022 Mar 13;12(3):704.
doi: 10.3390/diagnostics12030704.

Increased Levels of ICOS and ICOSL Are Associated to Pulmonary Arterial Hypertension in Patients Affected by Connective Tissue Diseases

Mattia Bellan  1   2   3 , Francesco Murano  1   2 , Federico Ceruti  1   2 , Cristina Piccinino  4 , Stelvio Tonello  1 , Rosalba Minisini  1 , Ailia Giubertoni  1   4 , Daniele Sola  2 , Roberta Pedrazzoli  2 , Veronica Maglione  1 , Giulia Francesca Manfredi  1   2 , Antonio Acquaviva  1   2 , Roberto Piffero  1   2 , Giuseppe Patti  1   4 , Mario Pirisi  1   2   3 , Pier Paolo Sainaghi  1   2   3
Affiliations

Increased Levels of ICOS and ICOSL Are Associated to Pulmonary Arterial Hypertension in Patients Affected by Connective Tissue Diseases

Mattia Bellan et al. Diagnostics (Basel). .

Abstract

Background: Pulmonary hypertension (PH) is a life-threatening complication of connective tissue diseases (CTD); in this study, we aimed at investigating the potential role of inducible co-stimulator (ICOS) and its ligand (ICOS-L) as biomarkers of PH in CTD.

Materials and methods: We recruited 109 patients: 84 CTD patients, 13 patients with CTD complicated by pulmonary arterial hypertension (PAH), and 12 subjects with PAH alone. All recruited patients underwent a complete clinical and instrumental assessment along with quantitative measurement of serum ICOS and ICOS-L.

Results: Independently of the underlying cause, patients with PAH were older and had a lower glomerular filtration rate. Interestingly, patients with both CTD-related and CTD-unrelated PAH had higher ICOS and ICOS-L serum concentrations than CTD patients (0.0001 for both). When compared to CTD patients, those affected by CTD-PAH showed higher ICOS (440 (240-600) vs. 170 (105-275) pg/mL, p = 0.0001) and ICOS-L serum concentrations (6000 (4300-7000) vs. 2450 (1500-4100) pg/mL; p = 0.0001). In a logistic regression, ICOS and ICOS-L were associated with a diagnosis of PAH, independently from age, gender, and renal function. The corresponding receiver operating characteristic (ROC) curves demonstrated a good diagnostic performance for both ICOS and ICOS-L.

Conclusions: ICOS and ICOS-L are increased in patients with PAH, irrespectively from the underlying cause, and represent promising candidate biomarkers for the diagnostic screening for PAH among CTDs patients.

Keywords: ICOS; ICOSL; connective tissue diseases; pulmonary arterial hypertension; systemic sclerosis.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Comparison of ICOS and ICOS-L between patients affected by CTD, with and without PAH. In (A) the plasma concentration of ICOS is compared between groups; (B) conversely reports the comparison of ICOS-L plasma concentrations. Abbreviations: CTD = connective tissue disease and PAH = pulmonary arterial hypertension.
Figure 2
Figure 2
ROC curves for ICOS and ICOS-L. The figures represent the ROC curves for ICOS (A) and ICOS-L (B) for the identification of PH.
See this image and copyright information in PMC

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