Low Circulating Monocytes Is in Parallel With Lymphopenia Which Predicts Poor Outcome in Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis-Associated Interstitial Lung Disease

Xia Lv; Yuyang Jin; Danting Zhang; Yixuan Li; Yakai Fu; Suli Wang; Yan Ye; Wanlong Wu; Shuang Ye; Bing Yan; Xiaoxiang Chen

doi:10.3389/fmed.2021.808875

Low Circulating Monocytes Is in Parallel With Lymphopenia Which Predicts Poor Outcome in Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis-Associated Interstitial Lung Disease

Front Med (Lausanne). 2022 Jan 17:8:808875. doi: 10.3389/fmed.2021.808875. eCollection 2021.

Authors

Xia Lv¹, Yuyang Jin¹, Danting Zhang¹, Yixuan Li¹, Yakai Fu¹, Suli Wang¹, Yan Ye¹, Wanlong Wu¹, Shuang Ye¹, Bing Yan², Xiaoxiang Chen¹

Affiliations

¹ Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
² Department of Rheumatology, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM)-associated interstitial lung disease (ILD) may progress rapidly and lead to high mortality within 6 or 12 months. Except for reported prognostic factors, simple but powerful prognostic biomarkers are still in need in practice. In this study, we focused on circulating monocyte and lymphocyte counts and their variation tendency in the early stage of ILD. A total of 351 patients from two inception anti-MDA5 antibody-positive cohorts were included in this study, with various treatment choices. Lymphocyte count remained lower in the first month after admission in the non-survivor patients. Although baseline monocyte count showed no significant differences, average monocyte count in the following 4 weeks was also lower in the non-survivor group. Based on the C-index and analysis by the "survminer" R package in the discovery cohort, we chose 0.24 × 109/L as the cutoff value for Mono W0-2, 0.61 × 109/L as the cutoff value for lymph W0-2, and 0.78 × 109/L as the cutoff value for peripheral blood mononuclear cell (PBMC) W0-2, to predict the 6-month all-cause mortality. The Kaplan-Meier survival curves and adjusted hazard ratio with age, gender, and the number of immunosuppressants used all validated that patients with lower average monocyte count, lower average lymphocyte count, or lower average PBMC count in the first 2 weeks after admission had higher 6-month death risk, no matter in the validation cohort or in the pooled data. Furthermore, flow cytometry figured out that non-classical monocytes in patients with anti-MDA5 antibody-positive DM were significantly lower than healthy controls and patients with DM without anti-MDA5 antibodies. In conclusion, this study elucidated the predictive value of monocyte and lymphocyte counts in the early stage and may help rheumatologists to understand the possible pathogenesis of this challenging disease.

Keywords: anti-MDA5 antibody-positive dermatomyositis; clinically amyopathic dermatomyositis; lymphocytopenia; monocyte; non-classical monocyte; prognostic biomarker; rapid progressive interstitial lung disease.