title: Lymphocyte aggregates persist and accumulate in the lungs of patients with idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with no known effective therapy. It is often assumed, but has not been objectively evaluated, that pulmonary inflammation subsides as IPF progresses. The goal of this work was to assess changes in the degree of inflammatory cell infiltration, particularly lymphocytic infiltration, over the duration of illness in IPF.
  
  
  METHODS
  Sixteen patients with confirmed IPF were identified in patients whom surgical lung biopsy (SLB) was performed in early disease, and in patients whom lung transplantation was subsequently performed in end stage disease. A numerical scoring system was used to histologically quantify the amount of fibrosis, honeycomb change, fibroblastic foci, and lymphocyte aggregates in each SLB and lung explant tissue sample. Analyses of quantitative scores were performed by comparing paired, matched samples of SLB to lung explant tissue.
  
  
  RESULTS
  Median time [1st, 3rd quartiles] from SLB to lung transplantation was 24 [15, 29] months. Histologic fibrosis and honeycomb change were more pronounced in the explant samples compared with SLB (P < 0.001 and P < 0.01, respectively), and most notably, higher numbers of lymphocyte aggregates were observed in the explant samples compared to SLB (P = 0.013). Immunohistochemical analyses revealed abundant CD3+ (T lymphocyte) and CD20+ (B lymphocyte) cells, but not CD68+ (macrophage) cells, within the aggregates.
  
  
  CONCLUSIONS
  Contrary to the frequent assumption, lymphocyte aggregates were present in greater numbers in advanced disease (explant tissue) compared to early disease (surgical lung biopsy). This finding suggests that active cellular inflammation continues in IPF even in severe end stage disease.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA ; Baltimore VA Medical Center, Baltimore, MD, USA.
authors.forename: Nevins W
authors.initials: NW
authors.lastname: Todd
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Scheraga
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Galvin
authors.forename: Aldo T
authors.initials: AT
authors.lastname: Iacono
authors.forename: E James
authors.initials: EJ
authors.lastname: Britt
authors.forename: Irina G
authors.initials: IG
authors.lastname: Luzina
authors.forename: Allen P
authors.initials: AP
authors.lastname: Burke
authors.forename: Sergei P
authors.initials: SP
authors.lastname: Atamas
keywords: idiopathic pulmonary fibrosis; inflammation; lymphocyte aggregates