Expansion of distinct peripheral blood myeloid cell subpopulations in patients with rheumatoid arthritis-associated interstitial lung disease

Jill A Poole; Kathryn E Cole; Geoffrey M Thiele; James E Talmadge; Bryant R England; Amy J Nelson; Angela Gleason; Aaron Schwab; Rohit Gaurav; Michael J Duryee; Kristina L Bailey; Debra J Romberger; Daniel Hershberger; Joel Van De Graaff; Sara M May; Rhonda Walenz; Bridget Kramer; Ted R Mikuls

doi:10.1016/j.intimp.2023.111330

Expansion of distinct peripheral blood myeloid cell subpopulations in patients with rheumatoid arthritis-associated interstitial lung disease

Int Immunopharmacol. 2024 Jan 25:127:111330. doi: 10.1016/j.intimp.2023.111330. Epub 2023 Dec 11.

Authors

Jill A Poole¹, Kathryn E Cole², Geoffrey M Thiele³, James E Talmadge⁴, Bryant R England⁵, Amy J Nelson³, Angela Gleason³, Aaron Schwab³, Rohit Gaurav³, Michael J Duryee⁵, Kristina L Bailey⁵, Debra J Romberger⁵, Daniel Hershberger³, Joel Van De Graaff⁵, Sara M May⁵, Rhonda Walenz³, Bridget Kramer³, Ted R Mikuls⁵

Affiliations

¹ Department of Internal Medicine, USA. Electronic address: japoole@unmc.edu.
² Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
³ Department of Internal Medicine, USA.
⁴ Department of Internal Medicine, USA; Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
⁵ Department of Internal Medicine, USA; Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA.

PMID: 38086271
DOI: 10.1016/j.intimp.2023.111330

Abstract

Objectives: Interstitial lung disease (ILD) is associated with significant mortality in rheumatoid arthritis (RA) patients with key cellular players remaining largely unknown. This study aimed to characterize inflammatory and myeloid derived suppressor cell (MDSC) subpopulations in RA-ILD as compared to RA, idiopathic pulmonary fibrosis (IPF) without autoimmunity, and controls.

Methods: Peripheral blood was collected from patients with RA, RA-ILD, IPF, and controls (N = 60, 15/cohort). Myeloid cell subpopulations were identified phenotypically by flow cytometry using the following markers:CD45,CD3,CD19,CD56,CD11b,HLA-DR,CD14,CD16,CD15,CD125,CD33. Functionality of subsets were identified with intracellular arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS) expression.

Results: There was increased intermediate (CD14⁺⁺CD16⁺) and nonclassical (CD14^+/-CD16⁺⁺) and decreased classical (CD14⁺⁺CD16^-) monocytes in RA, RA-ILD, and IPF vs. control. Intermediate monocytes were higher and classical monocytes were lower in RA-ILD vs. RA but not IPF. Monocytic (m)MDSCs were higher in RA-ILD vs. control and RA but not IPF. Granulocytic (g)MDSCs did not significantly differ. In contrast, neutrophils were increased in IPF and RA-ILD patients with elevated expression of Arg-1 sharing similar dimensional clustering pattern. Eosinophils were increased in RA-ILD vs. controls, RA and IPF. Across cohorts, iNOS was decreased in intermediate/nonclassical monocytes but increased in mMDSCs vs. classical monocytes. In RA-ILD, iNOS positive mMDSCs were increased versus classic monocytes.

Conclusions: Myeloid cell subpopulations are significantly modulated in RA-ILD patients with expansion of CD16⁺ monocytes, mMDSCs, and neutrophils, a phenotypic profile more aligned with IPF than other RA patients. Eosinophil expansion was unique to RA-ILD, potentially facilitating disease pathogenesis and providing a future therapeutic target.

Keywords: Biomarker; Eosinophil; Interstitial lung disease; MDSC; Monocyte; Neutrophil; Pulmonary fibrosis; Rheumatoid arthritis.

MeSH terms

Arthritis, Rheumatoid*
Humans
Idiopathic Pulmonary Fibrosis*
Lung Diseases, Interstitial*
Monocytes
Myeloid Cells