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Novel biomarker for pulmonary vascular disease in systemic sclerosis patients
E. Favoino1, G. Catacchio2, A. Mininni3, P. Ruscitti4, V. Riccieri5, V. Liakouli6, A. Corrado7, L. Navarini8, F. Ciccia9, P. Cipriani10, F.P. Cantatore11, G. Valesini12, R. Giacomelli13, F. Perosa14
- Rheumatic and Systemic Autoimmune Diseases Unit, Department of Interdisciplinary Medicine (DIM), University of Bari Medical School, Bari, Italy.
- Rheumatic and Systemic Autoimmune Diseases Unit, Department of Interdisciplinary Medicine (DIM), University of Bari Medical School, Bari, Italy.
- Rheumatic and Systemic Autoimmune Diseases Unit, Department of Interdisciplinary Medicine (DIM), University of Bari Medical School, Bari, Italy.
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy.
- Department of Clinical Internistic Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Italy.
- Rheumatology Section, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy.
- Rheumatology Unit, Department of Medical and Surgery Sciences, University of Foggia, Italy.
- Immunorheumatology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
- Rheumatology Section, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy.
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy.
- Rheumatology Unit, Department of Medical and Surgery Sciences, University of Foggia, Italy.
- Department of Clinical Internistic Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Italy.
- Rheumatology, Immunology and Clinical Medicine Unit, Department of Medicine, Campus Bio-Medico University, Rome, Italy.
- Rheumatic and Systemic Autoimmune Diseases Unit, Department of Interdisciplinary Medicine (DIM), University of Bari Medical School, Bari, Italy. federico.perosa@uniba.it
GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale)
CER15416
2022 Vol.40, N°10
PI 1956, PF 1963
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PMID: 35579087 [PubMed]
Received: 14/12/2021
Accepted : 28/02/2022
In Press: 29/04/2022
Published: 17/10/2022
Abstract
OBJECTIVES:
In systemic sclerosis (SSc) patients, pulmonary arterial hypertension (PAH), which is preceded by pulmonary vascular disease (PVD), is one the of major causes of morbidity and mortality. Given the higher risk of PAH among anti-CENP antibodies (ACA)+ patients, we previously characterised a subset of ACA+ patients, based on a differential reactivity of their ACA with the phage clone (pc4.2)-expressing peptide 4.2 (p4.2). There was a considerably greater prevalence of a low diffusing lung capacity for carbon monoxide (DLCO), an expression of PVD, among patients with high anti-pc4.2 Ab levels. Here we examine whether a similar clinical subgroup can be identified within a larger cohort of ACA+ patients, using the synthetic p4.2.
METHODS:
Clinical data and serum samples were collected from 134 ACA+ patients. Sera were screened for reactivity with p4.2 by indirect ELISA. Statistical analyses were performed to define any associations between anti-p4.2 Ab levels and PVD.
RESULTS:
Kendall’s analysis showed that anti-p4.2 Ab were directly associated with both a reduced DLCO and the presence of pulmonary fibrosis (PF). These associations were confirmed by Fisher’s exact test. At multivariate analysis, anti-p4.2 Ab was associated to DLCO<70, DLCO≤60, and PF. Moreover, multivariable analysis showed that only the association of anti-p4.2 Ab with DLCO<70, and not with DLCO≤60, was independent of PF.
CONCLUSIONS:
Anti-p4.2 Ab are able to identify SSc patients at high risk of developing PVD even in the absence of PF. Patients with high anti-p4.2 Ab levels should be strictly monitored for PVD onset and eventually PAH.
