title: The cellular composition of lymph nodes in the earliest phase of inflammatory arthritis.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease of unknown aetiology. Recent work has shown that systemic autoimmunity precedes synovial inflammation, and animal models have suggested that changes in the lymph nodes may precede those in the synovial tissue. Therefore, we investigated the cellular composition of the lymph node in the earliest phases of inflammatory arthritis.
  
  
  METHODS
  Thirteen individuals positive for immunoglobulin M (IgM) rheumatoid factor and/or anticitrullinated protein antibodies without arthritis were included. Additionally, we studied 14 early arthritis patients (arthritis duration ≤6 months, naïve for disease-modifying antirheumatic drugs), and eight healthy controls. All subjects underwent ultrasound-guided inguinal lymph node biopsy. Different T- and B-lymphocyte subsets were analysed by multicolour flow cytometry.
  
  
  RESULTS
  There was an increase in activated CD69 CD8 T cells and CD19 B cells in early arthritis patients compared with healthy controls. We also observed a trend towards increased CD19 B cells in autoantibody-positive individuals without arthritis compared with healthy controls.
  
  
  CONCLUSIONS
  This exploratory study suggests that there is increased immune cell activation within lymph nodes of early arthritis patients as well as in autoantibody-positive individuals at risk of developing RA. This method provides a unique tool to investigate immunological changes in the lymph node compartment in the earliest phases of inflammatory arthritis.
authors: Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. e.g.vanbaarsen@amc.uva.nl
authors: L G M
authors: LG
authors: van Baarsen
authors: M J H
authors: MJ
authors: de Hair
authors: T H
authors: TH
authors: Ramwadhdoebe
authors: I J A J
authors: IJ
authors: Zijlstra
authors: M
authors: M
authors: Maas
authors: D M
authors: DM
authors: Gerlag
authors: P P
authors: PP
authors: Tak
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D001323:Autoantibodies / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D042241:Early Diagnosis; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000276:immunology; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D012217:Rheumatoid Factor / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000473:pathology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D007075:Immunoglobulin M; D037181:Lectins, C-Type; D010456:Peptides, Cyclic; D012217:Rheumatoid Factor; D000099192:CD69 Antigens; C487763:cyclic citrullinated peptide
keywords: B cells; Early Rheumatoid Arthritis; T Cells
references: Arthritis Rheum. 2010 Mar;62(3):694-704
references: 20131234
references: Arthritis Rheum. 1997 Apr;40(4):598-609
references: 9125240
references: Ann Rheum Dis. 2012 Nov;71(11):1911-2
references: 22689316
references: Arthritis Rheum. 2002 Apr;46(4):894-8
references: 11953964
references: Inflammation. 1999 Apr;23(2):153-65
references: 10213271
references: Arthritis Rheum. 2003 Oct;48(10):2741-9
references: 14558078
references: Nat Immunol. 2007 Dec;8(12):1295-301
references: 18026082
references: Ann Rheum Dis. 2012 May;71(5):638-41
references: 22387728
references: Cell Immunol. 1991 Nov;138(1):251-9
references: 1833075
references: Ann Rheum Dis. 2008 Jun;67(6):860-6
references: 17644543
references: J Rheumatol. 1993 Aug;20(8):1278-81
references: 7693940
references: Rheumatology (Oxford). 2001 Nov;40(11):1211-20
references: 11709604
references: Arthritis Rheum. 2004 Feb;50(2):380-6
references: 14872479
references: Ann Rheum Dis. 2010 Mar;69(3):490-4
references: 19363023
references: Arthritis Res Ther. 2008;10 Suppl 1:S1
references: 19007421
references: Arthritis Rheum. 2002 Feb;46(2):298-308
references: 11840432
references: Arthritis Rheum. 1985 May;28(5):485-9
references: 4004958
references: Arthritis Rheum. 2002 Feb;46(2):283-5
references: 11840429
references: J Immunol. 2010 Jun 1;184(11):6142-50
references: 20435928
references: Ann Rheum Dis. 2011 May;70(5):772-7
references: 21177292