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Thursday, February 15th, 2018
Table of Contents

1 Introduction
5 PMID
 [F] Diseases Research  / PubMed Research Articles  /
Transcriptional Profiling of Synovial Macrophages using Minimally Invasive Ultrasound-Guided Synovial Biopsies in Rheumatoid Arthritis.

PubMed

 

Resource

Arthritis & rheumatology (Hoboken, N.J.) Feb ; ()

Authors

Mandelin AM1; Homan PJ2; Shaffer AM3; Cuda CM4; Dominguez ST5; Bacalao E6; Carns M7; Hinchcliff M8; Lee J9; Aren K10; Thakrar A11; Montgomery AB12; Louis Bridges S13; Bathon JM14; Atkinson JP15; Fox DA16; Matteson EL17; Buckley CD18; Pitzalis C19; Parks D20; Hughes LB21; Geraldino-Pardilla L22; Ike R23; Phillips K24; Wright K25; Filer A26; Kelly S27; Ruderman EM28; Morgan V29; Abdala-Valencia H30; Misharin AV31; Budinger GS32; Bartom ET33; Pope RM34; Perlman H35; Winter DR36;

Author Information
  • 1Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 2Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 3Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 4Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 5Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 6Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 7Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 8Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 9Department of Preventive Medicine, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 10Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 11Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 12Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 13Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, AL.
  • 14Department of Medicine, Division of Rheumatology, Columbia University, College of Physicians and Surgeons, New York, NY.
  • 15Department of Medicine, Division of Rheumatology, Washington University School of Medicine, Saint Louis, MO.
  • 16Department of Internal Medicine, University of Michigan, Division of Rheumatology and Clinical Autoimmunity Center of Excellence, University of Michigan School of Medicine, Ann Arbor, MI.
  • 17Department of Internal Medicine, Division of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN.
  • 18Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, UK.
  • 19William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • 20Department of Medicine, Division of Rheumatology, Washington University School of Medicine, Saint Louis, MO.
  • 21Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, AL.
  • 22Department of Medicine, Division of Rheumatology, Columbia University, College of Physicians and Surgeons, New York, NY.
  • 23Department of Internal Medicine, University of Michigan, Division of Rheumatology and Clinical Autoimmunity Center of Excellence, University of Michigan School of Medicine, Ann Arbor, MI.
  • 24Department of Internal Medicine, University of Michigan, Division of Rheumatology and Clinical Autoimmunity Center of Excellence, University of Michigan School of Medicine, Ann Arbor, MI.
  • 25Department of Internal Medicine, Division of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN.
  • 26Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, UK.
  • 27William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • 28Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 29Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 30Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 31Department of Medicine, Division of Pulmonary and Critical Care, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 32Department of Medicine, Division of Pulmonary and Critical Care, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 33Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 34Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 35Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.
  • 36Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine Chicago, IL.

Abstract

OBJECTIVE: Currently, there are no reliable biomarkers for predicting therapeutic response in patients with rheumatoid arthritis (RA). The synovium may unlock critical information for determining efficacy as reduction in numbers of sublining synovial macrophages remains the most reproducible biomarker. Thus, a clinically actionable method for collection of synovial tissue, which can be analyzed using high-throughput strategies, must become a reality.

METHODS: Rheumatologists at six United States academic sites were trained in minimally invasive ultrasound-guided synovial tissue biopsy. Histology, fluorescence-activated cell sorting and RNA-seq were performed on biopsy synovial tissue from patients with RA and compared with osteoarthritis (OA) samples. An optimized protocol for digesting synovial tissue was developed to generate high quality RNA-seq libraries from isolated macrophage populations. Associations were determined between macrophage transcriptional profiles and clinical parameters of RA patients.

RESULTS: Patients with RA reported minimal adverse effects in response to synovial biopsy. Comparable RNA quality was observed between synovial tissue and isolated macrophages from patients with RA and OA. Whole tissue samples from patients with RA demonstrated a high degree of transcriptional heterogeneity. In contrast, the transcriptional profile of isolated RA synovial macrophages highlighted a subpopulation of patients and identified six novel transcriptional modules that were associated with disease activity and therapy.

CONCLUSION: Performance of synovial tissue biopsies by rheumatologists in the United States is feasible and generates high-quality samples for research. By utilizing cutting-edge technologies on synovial biopsies with corresponding clinical information, a precision-based medicine approach for patients with RA is attainable. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

PMID

29439295

Others

Publication Type: Journal Article


This article is licensed under the the National Library of Medicine License. It uses material from the PubMed National Library of Medicine Data.


Last Modified:   2016-03-27


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