title: Intrapulmonary Human Cytomegalovirus Replication in Lung Transplant Recipients Is Associated With a Rise of CCL-18 and CCL-20 Chemokine Levels.
abstract: BACKGROUND
  In lung transplant recipients (LTRs), human cytomegalovirus (HCMV) DNA detection in the bronchoalveolar lavage fluid (BALF) indicates HCMV replication in the pulmonary compartment. Such local HCMV replication episodes may remain asymptomatic or may lead to symptomatic HCMV disease. Here, we investigated LTRs with intrapulmonary HCMV replication for the chemokines CCL-18 and CCL-20. In particular, we analyzed whether these chemokines rise in the allograft and/or the blood and are associated with HCMV disease.
  
  
  METHODS
  CCL-18 and CCL-20 levels were quantitated by ELISA in BALF and serum samples from 60 LTRs. During the posttransplant follow-up, these LTRs displayed HCMV DNA detection in the BALF by PCR, whereas other infectious agents were undetectable. Furthermore, we investigated samples from 10 controls who did not display any HCMV replication episode during the follow-up.
  
  
  RESULTS
  HCMV replication in the allograft was associated with a significant increase of CCL-18 and CCL-20 BALF levels (P < 0.001, Wilcoxon signed-rank test) and a significant rise of CCL-20 (P < 0.0001, Wilcoxon signed-rank test) but not of CCL-18 in the blood. In controls, no such chemokine increase was observed. Furthermore, CCL-18 BALF levels were significantly higher in 8 LTRs who additionally developed HCMV disease, as compared with the other 52 patients in whom HCMV replication remained asymptomatic (P < 0.001, Mann-Whitney U test).
  
  
  CONCLUSIONS
  HCMV replication in the allograft causes an intrapulmonary increase of CCL-18 and CCL-20 and a systemic rise of CCL-20 serum levels. Strong intrapulmonary CCL-18 responses are associated with symptomatic HCMV disease, proposing that CCL-18 BALF levels could serve as a marker.
authors.affiliation: 1 Department of Virology, Medical University of Vienna, Vienna, Austria. 2 Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Weseslindtner
authors.forename: Irene
authors.initials: I
authors.lastname: Görzer
authors.forename: Kevin
authors.initials: K
authors.lastname: Roedl
authors.forename: Erik
authors.initials: E
authors.lastname: Küng
authors.forename: Peter
authors.initials: P
authors.lastname: Jaksch
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Puchhammer-Stöckl
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054418:Chemokine CCL20 / Q000097:blood*; D019742:Chemokines, CC / Q000378:metabolism*; D003587:Cytomegalovirus / Q000235:genetics / Q000254:growth & development*; D003586:Cytomegalovirus Infections / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D013997:Time Factors; D066027:Transplant Recipients; D016896:Treatment Outcome; D015854:Up-Regulation; D014779:Virus Replication; D055815:Young Adult
chemical_list: D015415:Biomarkers; C111792:CCL18 protein, human; C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D004279:DNA, Viral