Circulating Hybrid M1/M2 Monocytes/Macrophages in Systemic Sclerosis Patients with Lung Involvement

Maurizio Cutolo¹, Amelia Chiara Trombetta², Veronica Tomatis³, Sabrina Paolino⁴, Carmen Pizzorni¹, Vanessa Smith⁵, Paola Contini⁶, Paola Montagna³, Renata Brizzolara² and Stefano Soldano³, ¹Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, San Martino Polyclinic Hospital, Genoa, Italy, Genoa, Italy, ²Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, IRCCS Polyclinic San Martino, University of Genoa, Genoa, Italy, ³Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, IRCCS Polyclinic San Martino, University of Genoa, Genova, Italy, ⁴Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, San Martino Polyclinic Hospital, Genoa, Italy, Genova, Italy, ⁵Department of Rheumatology, Ghent University Hospital, Ghent, Belgium, ⁶Division of Clinical Immunology, Department of Internal Medicine, University of Genova, IRCCS Polyclinic San Martino, Genova, Italy, Genova, Italy

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: interstitial lung disease, macrophages and systemic sclerosis

Session Information

Date: Monday, October 22, 2018

Title: Innate Immunity Poster

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Systemic sclerosis (SSc) is an autoimmune disease characterized by immune system alterations, vasculopathy and fibrosis [1]. SSc-related interstitial lung disease (ILD) represents a common and early complication of SSc, being the leading cause of mortality [2]. Monocytes/macrophages seem to have a key role in SSc-related ILD. Interestingly, the classically (M1) and alternatively (M2) activated monocyte/macrophage phenotype categorization is currently under revision [3]. Our aim was to evaluate if circulating monocyte/macrophage phenotype could be hypothesized as a pathogenic factor and/or used as biomarker for SSc-related ILD. To this purpose we developed a wide phenotype characterization of circulating monocyte/macrophage subsets in SSc patients and evaluated relations with lung involvement parameters.

Methods: A single centre, cross-sectional study was performed, in fifty-five consecutive SSc patients (50 females/5 males, mean age of 63±13 years, 36 with a diffused cutaneous disease form and 19 with a limited cutaneous disease). All clinical and instrumental tests requested for SSc follow up and in particular: lung computed tomography (CT) scan, pulmonary function tests (PFTs), Doppler echocardiography with systolic pulmonary artery pressure (sPAP) measurement, blood pro-hormone of brain natriuretic peptide evaluation, were performed in each patient. Flow-cytometry characterization of circulating monocytes/macrophages was performed using surface markers attributed both to M1 and M2 cell subsets. Non-parametric tests were used for statistical analysis and any p-value lower than 0.05 was considered as statistically significant.

Results: Several mixed M1/M2 monocyte/macrophage subsets showed higher percentages in patients positive for anti-topoisomerase antibody, a well-known lung involvement predictor. A higher percentage of circulating cells positive for both CD204, CD163, CD206 (M2 markers) and TLR4, CD80, CD86 (M1 markers), was identified to characterize patients affected by SSc-related ILD and higher systolic pulmonary artery pressure. Higher percentages of circulating M1/M2 subsets showed a linear negative correlation with diffusion lung capacity of carbon monoxide (DLCO)%. A FVC/DLCO ratio higher than 1.5 correlated with higher circulating M1/M2 percentages.

Conclusion: The present study shows for the first time, through a wide flow cytometry surface marker analysis, that higher circulating mixed M1/M2 monocyte/macrophage cell percentage significantly correlated with anti-topoisomerase antibody positivity, ILD and sPAP in SSc, opening the path for research on their possible role as pathogenic or biomarker elements for SSc lung involvement. References.[1] Cutolo M, et al. Nat Rev Rheumatol 2015; 11:569-71. [2] Steen VD, et al. Ann Rheum Dis 2007;66:940-4. [3] Christmann RB, et al. Arthritis Rheumatol. 2014;66:714-25.

Disclosure: M. Cutolo, Bristol Myers Squibb, 2; A. C. Trombetta, None; V. Tomatis, None; S. Paolino, None; C. Pizzorni, None; V. Smith, None; P. Contini, None; P. Montagna, None; R. Brizzolara, None; S. Soldano, None.

To cite this abstract in AMA style:

Cutolo M, Trombetta AC, Tomatis V, Paolino S, Pizzorni C, Smith V, Contini P, Montagna P, Brizzolara R, Soldano S. Circulating Hybrid M1/M2 Monocytes/Macrophages in Systemic Sclerosis Patients with Lung Involvement [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/circulating-hybrid-m1-m2-monocytes-macrophages-in-systemic-sclerosis-patients-with-lung-involvement/. Accessed .

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