Signs of immune activation and local inflammation are present in the bronchial tissue of patients with untreated early rheumatoid arthritis

• Published in: Annals of the rheumatic diseases Vol. 75; no. 9; pp. 1722 - 1727
• Main Authors: Reynisdottir, Gudrun, Olsen, Helga, Joshua, Vijay, Engström, Marianne, Forsslund, Helena, Karimi, Reza, Sköld, C Magnus, Nyren, Sven, Eklund, Anders, Grunewald, Johan, Catrina, Anca I
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.09.2016
• Subjects: Adult; Aged; Antibodies; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Autoantibodies - analysis; Autoantibodies - immunology; B-Lymphocytes - immunology; Biomarkers - analysis; Biopsy; Bronchi - immunology; Bronchi - pathology; Bronchitis; Bronchoalveolar Lavage Fluid - immunology; Bronchoscopy; Case-Control Studies; Early Diagnosis; Female; Histology; Humans; Inflammation; Lavage; Lung diseases; Lungs; Lymphocyte Count; Male; Medicin och hälsovetenskap; Middle Aged; Peptides, Cyclic - immunology; Plasma Cells - immunology; Proteins; Rheumatoid arthritis; T-Lymphocyte Subsets - immunology; United States > US; Rheumatoid Arthritis; Ant-CCP; T Cells
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2015-208216

ObjectivesEvents 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.MethodsTwenty-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.ResultsLymphocyte 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.ConclusionsSigns 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.