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Increased plasma levels of Gas6 and its soluble tyrosine kinase receptors Mer and Axl are associated with immunological activity and severity of lupus nephritis.
M. Bellan1, M. Quaglia2, A. Nerviani3, D. Mauro4, M. Lewis5, F. Goegan6, A. Gibbin7, S. Pagani8, L. Salmi9, L. Molinari10, L.M. Castello11, G.C. Avanzi12, V. Cantaluppi13, M. Pirisi14, P.P. Sainaghi15, C. Pitzalis16
- Department of Translational Medicine, Università del Piemonte Orientale, Novara; Internal Medicine Division, Maggiore della Carità Hospital, Novara; IRCAD, Interdisciplinary Research Center of Autoimmune Diseases, Novara, Italy. bellanmattia@yahoo.it
- Department of Translational Medicine, Università del Piemonte Orientale, Novara; IRCAD, Interdisciplinary Research Center of Autoimmune Diseases, Novara; and Division of Nephrology and Renal Transplantation, Maggiore della Carità Hospital, Novara, Italy.
- Centre for Experimental Medicine and Rheumatology, Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, UK.
- Centre for Experimental Medicine and Rheumatology, Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, UK.
- Centre for Experimental Medicine and Rheumatology, Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, UK.
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.
- Department of Translational Medicine, Università del Piemonte Orientale, Novara; and Internal Medicine Division, Maggiore della Carità Hospital, Novara, Italy.
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.
- Department of Translational Medicine, Università del Piemonte Orientale, Novara; and Emergency Medicine Department, Maggiore della Carità Hospital, Novara, Italy.
- Department of Translational Medicine, Università del Piemonte Orientale, Novara; and Emergency Medicine Department, Maggiore della Carità Hospital, Novara, Italy.
- Department of Translational Medicine, Università del Piemonte Orientale, Novara; IRCAD, Interdisciplinary Research Center of Autoimmune Diseases, Novara; and Division of Nephrology and Renal Transplantation, Maggiore della Carità Hospital, Novara, Italy.
- Department of Translational Medicine, Università del Piemonte Orientale, Novara; and Internal Medicine Division, Maggiore della Carità Hospital, Novara, Italy.
- Department of Translational Medicine, Università del Piemonte Orientale, Novara; Internal Medicine Division, Maggiore della Carità Hospital, Novara; IRCAD, Interdisciplinary Research Center of Autoimmune Diseases, Novara, Italy.
- Centre for Experimental Medicine and Rheumatology, Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, UK.
CER12946
2021 Vol.39, N°1
PI 0132, PF 0138
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PMID: 32573415 [PubMed]
Received: 12/11/2019
Accepted : 17/03/2020
In Press: 04/06/2020
Published: 05/02/2021
Abstract
OBJECTIVES:
Growth arrest-specific 6 (Gas6) and its receptors have been shown to play a crucial role in the homeostasis of the innate immune system by regulating apoptosis and inflammation. We aimed to verify whether an impairment of this system is associated with systemic lupus erythematosus (SLE) disease activity and with lupus nephritis (LN).
METHODS:
Plasma Gas6 and the soluble cleaved form of the receptors MerTK (sMer) and Axl (sAxl) concentrations were measured in n=59 SLE patients (n=44 with nephritis, 75%) and analysed in relationship to clinical and laboratory data.
RESULTS:
Patients with LN were characterised by higher Gas6 (19.0 ng/mL [16.8–24.5] vs. 16.5 ng/mL [13.89–18.91]; p=0.03) and sAxl plasma levels than those without LN (31.36 ng/mL [25.1–41.4] vs. 20.2 ng/mL [15.6–30.7]; p=0.03); conversely sMer plasma concentrations were similar between groups. All the three biomarkers studied were directly correlated to creatinine and daily proteinuria, being inversely related to creatinine clearance. 39 patients had a proteinuria level of <0.5 mg/day, 14 between 0.5 and 3.5 mg/day and 5 had ≥3.5 g/day; Gas6, sAxl and sMer plasma concentrations significantly increased for increasing degree of proteinuria (test for trend p=0.0002; p=0.02; p=0.009, respectively).These correlations were confirmed in multiple linear regression analysis models accounting for gender, age, disease duration and concomitant treatment.
CONCLUSIONS:
Plasma Gas6, sAxl and sMer concentrations are associated with the severity of LN in patients affected by SLE. The excess cleavage of TAM receptors might contribute to LN pathogenesis.
