1. Elevated serum Krebs von den Lungen-6 in systemic sclerosis: a marker of lung fibrosis and severity of the disease
- Author
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Jean-Robert Harlé, Xavier Heim, Noémie Resseguier, Mikael Ebbo, Nathalie Bardin, Carine Gomez, Brigitte Granel, Daniel Bertin, Audrey Benyamine, Gilles Kaplanski, Pascal Rossi, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Laboratoire d'immunologie, Pôle de Biologie, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), UPRES EA220, Lung Transplantation Department, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Centre National de la Recherche Scientifique (CNRS), Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique (LOBIP), Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)
- Subjects
Male ,Vital capacity ,[SDV]Life Sciences [q-bio] ,Pulmonary Fibrosis ,Vital Capacity ,Severity of Illness Index ,Gastroenterology ,Pulmonary function testing ,0302 clinical medicine ,Anti-topoisomerase 1 antibody (Scl70) ,Risk Factors ,Odds Ratio ,Immunology and Allergy ,Lung volumes ,030212 general & internal medicine ,Lung ,Interstitial lung disease ,Middle Aged ,respiratory system ,Krebs von den Lungen-6 ,Up-Regulation ,3. Good health ,medicine.anatomical_structure ,DNA Topoisomerases, Type I ,Antibodies, Antinuclear ,Systemic sclerosis ,Biomarker (medicine) ,Female ,France ,medicine.medical_specialty ,Centromere ,Immunology ,03 medical and health sciences ,Rheumatology ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Clinical significance ,Disease severity ,Aged ,030203 arthritis & rheumatology ,Scleroderma, Systemic ,business.industry ,Mucin-1 ,Total Lung Capacity ,medicine.disease ,respiratory tract diseases ,Logistic Models ,Multivariate Analysis ,Pulmonary Diffusing Capacity ,Lung fibrosis ,Lung Diseases, Interstitial ,Tomography, X-Ray Computed ,business ,Biomarkers - Abstract
International audience; We aimed to assess the clinical significance of Krebs von den Lungen-6 (KL-6) in the diagnosis and severity of interstitial lung disease (ILD) in a French cohort of patients with systemic sclerosis (SSc). Serum KL-6 concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA) in 75 SSc patients. Patients were divided into two groups according to the presence of interstitial lung disease (SSc-ILD versus SSc-without ILD) on chest High-Resolution Computed Tomography. Pulmonary function tests, main manifestations and severity of the lung disease (Medsger's severity scale) were collected. KL-6 serum concentrations were significantly higher in SSc-ILD patients than in those without ILD (p < 10(-4)) and were inversely correlated with forced vital capacity, total lung capacity and diffuse lung capacity of carbon monoxide. Serum KL-6 level superior to 872 U/ml appeared as the optimal cut-off value associated with ILD. Patients with a restrictive pulmonary syndrome and dyspnoea had significant higher KL-6 serum concentrations. SSc patients with anti-topoisomerase 1 antibodies had higher KL-6 serum levels than patients with anti-centromere antibodies (p < 10(- 4)). ILD and anti-topoisomerase 1 antibodies were independent factors associated with KL-6 in multivariate analysis. Interestingly, KL-6 serum concentrations positively increased with the patient lung severity. Our study confirms that KL-6 is an accurate biomarker for the diagnosis of SSc-ILD in a French cohort of patients. High KL-6 levels should prompt physicians to assess ILD with pulmonary imaging and pulmonary functions tests. Prospective clinical studies are still required to determine whether levels of KL-6 might predict progression of ILD as well as its usefulness in the timing of therapeutic intervention.
- Published
- 2018