title: Signs of immune activation and local inflammation are present in the bronchial tissue of patients with untreated early rheumatoid arthritis.
abstract: Events in the lungs might contribute to generation of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). We investigated if signs of immune activation are present in bronchial biopsies and bronchoalveolar lavage (BAL) of patients with early-untreated RA without clinical signs of lung involvement.
  
  
  
  Twenty-four patients with RA with symptom duration <1 year and naïve to disease-modifying antirheumatic drugs were subjected to bronchoscopy where BAL and mucosal bronchial biopsies were retrieved. For comparison, 15 bronchial biopsies and 79 BAL samples from healthy volunteers were available. Histological examination was performed to evaluate lymphocyte infiltration, presence of immune cells (T and B cells, plasma cells, dendritic cells and macrophages) and immune activation markers. Cell composition of BAL samples was analysed by differential counting and T cell subsets by flow cytometry.
  
  
  
  Lymphocyte infiltration was more frequently found in ACPA-positive patients (50%) as compared with ACPA-negative patients (17%) and controls (13%). Germinal centres, B cells and plasma cells were only found in ACPA-positive patients. The frequency of T cells in bronchial biopsies of patients with ACPA-positive RA was positively associated with expression of immune activation markers. BAL samples of patients with ACPA-positive, but not ACPA-negative, RA had significantly higher relative numbers of lymphocytes and expressed higher levels of activation markers compared with controls.
  
  
  
  Signs of immune cell accumulation and activation are present both in the bronchial tissue and in BAL of untreated patients with early RA without concomitant lung disease, strengthening the role of the lung compartment as an important player in ACPA-positive RA.
authors.affiliation: Rheumatology Unit, Department of Medicine, Solna, Karolinska University Hospital and Institutet, Stockholm, Sweden.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Reynisdottir
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Helga
authors.initials: H
authors.lastname: Olsen
authors.affiliation: Rheumatology Unit, Department of Medicine, Solna, Karolinska University Hospital and Institutet, Stockholm, Sweden.
authors.forename: Vijay
authors.initials: V
authors.lastname: Joshua
authors.affiliation: Rheumatology Unit, Department of Medicine, Solna, Karolinska University Hospital and Institutet, Stockholm, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Engström
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Forsslund
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Reza
authors.initials: R
authors.lastname: Karimi
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: C Magnus
authors.initials: CM
authors.lastname: Sköld
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Nyren
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Eklund
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Grunewald
authors.affiliation: Rheumatology Unit, Department of Medicine, Solna, Karolinska University Hospital and Institutet, Stockholm, Sweden.
authors.forename: Anca I
authors.initials: AI
authors.lastname: Catrina
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D001980:Bronchi / Q000276:immunology* / Q000473:pathology; D001991:Bronchitis; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016022:Case-Control Studies; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
keywords: Ant-CCP; Rheumatoid Arthritis; T Cells