Rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren's syndrome shared megakaryocyte expansion in peripheral blood

Yukai Wang; Xuezhen Xie; Chengpeng Zhang; Miaotong Su; Sini Gao; Jing Wang; Changhao Lu; Qisheng Lin; Jianqun Lin; Marco Matucci-Cerinic; Daniel E Furst; Guohong Zhang

doi:10.1136/annrheumdis-2021-220066

Rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren's syndrome shared megakaryocyte expansion in peripheral blood

Ann Rheum Dis. 2022 Mar;81(3):379-385. doi: 10.1136/annrheumdis-2021-220066. Epub 2021 Aug 30.

Authors

Affiliations

¹ Department of Rheumatology and Immunology, Shantou Central Hospital, Shantou, China.
² Department of Pathology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China.
³ Department of Internal Medicine, University of Florence, Firenze, Italy.
⁴ Rheumatology, University of California Los Angeles, Los Angeles, California, USA.
⁵ Department of Pathology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China g_ghzhang@stu.edu.cn.

^# Contributed equally.

Abstract

Objectives: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) share many clinical manifestations and serological features. The aim of this study was to identify the common transcriptional profiling and composition of immune cells in peripheral blood in these autoimmune diseases (ADs).

Methods: We analysed bulk RNA-seq data for enrichment of biological processes, transcription factors (TFs) and deconvolution-based immune cell types from peripheral blood mononuclear cells (PBMCs) in 119 treatment-naive patients (41 RA, 38 pSS, 28 SLE and 12 polyautoimmunity) and 20 healthy controls. The single-cell RNA-seq (scRNA-seq) and flow cytometry had been performed to further define the immune cell subsets on PBMCs.

Results: Similar transcriptional profiles and common gene expression signatures associated with nucleosome assembly and haemostasis were identified across RA, SLE, pSS and polyautoimmunity. Distinct TF ensembles and gene regulatory network were mainly enriched in haematopoiesis. The upregulated cell-lineage-specific TFs PBX1, GATA1, TAL1 and GFI1B demonstrated a strong gene expression signature of megakaryocyte (MK) expansion. Gene expression-based cell type enrichment revealed elevated MK composition, specifically, CD41b⁺CD42b⁺ and CD41b⁺CD61⁺ MKs were expanded, further confirmed by flow cytometry in these ADs. In scRNA-seq data, MKs were defined by TFs PBX1/GATA1/TAL1 and pre-T-cell antigen receptor gene, PTCRA. Cellular heterogeneity and a distinct immune subpopulation with functional enrichment of antigen presentation were observed in MKs.

Conclusions: The identification of MK expansion provided new insights into the peripheral immune cell atlas across RA, SLE, pSS and polyautoimmunity. Aberrant regulation of the MK expansion might contribute to the pathogenesis of these ADs.

Keywords: Sjogren's syndrome; rheumatoid arthritis; systemic lupus erythematosus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Arthritis, Rheumatoid / blood*
Arthritis, Rheumatoid / immunology
Autoimmunity / genetics*
Case-Control Studies
Female
Flow Cytometry
Gene Expression Profiling
Humans
Leukocytes, Mononuclear
Lupus Erythematosus, Systemic / blood*
Lupus Erythematosus, Systemic / immunology
Male
Megakaryocytes / immunology*
Middle Aged
RNA-Seq
Sjogren's Syndrome / blood*
Sjogren's Syndrome / immunology
Transcriptome / immunology