title: Differences in systemic adaptive immunity contribute to the 'frequent exacerbator' COPD phenotype.
abstract: Some COPD patients are more susceptible to exacerbations than others. Mechanisms underlying these differences in susceptibility are not well understood. We hypothesized that altered cell mediated immune responses may underlie a propensity to suffer from frequent exacerbations in COPD.
  
  
  
  Peripheral blood mononuclear cells (PBMCs) were obtained from 24 stable COPD patients, eight frequent exacerbators (≥3 diary-card exacerbations/year) and 16 infrequent exacerbators (< 3 diary-card exacerbations/year). Detailed multi-parameter flow cytometry was used to study differences in innate and adaptive systemic immune function between frequent and infrequently exacerbating COPD patients.
  
  
  
  The 24 COPD patients had a mean (SD) age of 76.3 (9.4) years and FEV11.43 (0.60)L, 53.3 (18.3)% predicted. PBMCs of frequent exacerbators (FE) contained lower frequencies of CD4+ T central memory cells (CD4+ Tcm) compared to infrequent exacerbators (IE) (FE = 18.7 %; IE = 23.9 %; p = 0.035). This observation was also apparent in absolute numbers of CD4+ Tcm cells (FE = 0.17 × 10^6/mL; IE = 0.25 × 10^6/mL; p = 0.035). PBMCs of FE contained a lower frequency of CD8+ T effector memory cells expressing HLA-DR (Human Leukocyte Antigen - D Related) compared to IE COPD patients (FE = 22.7 %; IE = 31.5 %; p = 0.007).
  
  
  
  Differences in the adaptive systemic immune system might associate with exacerbation susceptibility in the 'frequent exacerbator' COPD phenotype. These differences include fewer CD4+ T central memory cells and CD8+ T effector memory cells.
  
  
  
  Not applicable.
authors: Department of Respiratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.|UCL Respiratory, University College London, London, UK.
authors: Jasper X
authors: JX
authors: Geerdink
authors: Department of Respiratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors: Sami O
authors: SO
authors: Simons
authors: Institute of Immunity and Transplantation, University College London, London, UK.
authors: Rebecca
authors: R
authors: Pike
authors: Institute of Immunity and Transplantation, University College London, London, UK.
authors: Hans J
authors: HJ
authors: Stauss
authors: Department of Respiratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors: Yvonne F
authors: YF
authors: Heijdra
authors: UCL Respiratory, University College London, London, UK. j.hurst@ucl.ac.uk.
authors: John R
authors: JR
authors: Hurst
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007156:Immunologic Memory; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D016014:Linear Models; D008168:Lung / Q000276:immunology / Q000503:physiopathology; D008297:Male; D015999:Multivariate Analysis; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D012720:Severity of Illness Index
keywords: Adaptive immunity; COPD; COPD exacerbation; Flow cytometry; Respiratory immunology