title: CXCR3 chemokine ligands during respiratory viral infections predict lung allograft dysfunction.
abstract: Community-acquired respiratory viruses (CARV) can accelerate the development of lung allograft dysfunction, but the immunologic mechanisms are poorly understood. The chemokine receptor CXCR3 and its chemokine ligands, CXCL9, CXCL10 and CXCL11 have roles in the immune response to viruses and in the pathogenesis of bronchiolitis obliterans syndrome, the predominant manifestation of chronic lung allograft rejection. We explored the impact of CARV infection on CXCR3/ligand biology and explored the use of CXCR3 chemokines as biomarkers for subsequent lung allograft dysfunction. Seventeen lung transplant recipients with CARV infection had bronchoalveolar lavage fluid (BALF) available for analysis. For comparison, we included 34 BALF specimens (2 for each CARV case) that were negative for infection and collected at a duration posttransplant similar to a CARV case. The concentration of each CXCR3 chemokine was increased during CARV infection. Among CARV infected patients, a high BALF concentration of either CXCL10 or CXCL11 was predictive of a greater decline in forced expiratory volume in 1 s, 6 months later. CXCR3 chemokine concentrations provide prognostic information and this may have important implications for the development of novel treatment strategies to modify outcomes after CARV infection.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, at UCLA, Los Angeles, CA, USA. sweigt@mednet.ucla.edu
authors.forename: S S
authors.initials: SS
authors.lastname: Weigt
authors.forename: A
authors.initials: A
authors.lastname: Derhovanessian
authors.forename: E
authors.initials: E
authors.lastname: Liao
authors.forename: S
authors.initials: S
authors.lastname: Hu
authors.forename: A L
authors.initials: AL
authors.lastname: Gregson
authors.forename: B M
authors.initials: BM
authors.lastname: Kubak
authors.forename: R
authors.initials: R
authors.lastname: Saggar
authors.forename: R
authors.initials: R
authors.lastname: Saggar
authors.forename: V
authors.initials: V
authors.lastname: Plachevskiy
authors.forename: M C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: J P
authors.initials: JP
authors.lastname: Lynch
authors.forename: A
authors.initials: A
authors.lastname: Ardehali
authors.forename: D J
authors.initials: DJ
authors.lastname: Ross
authors.forename: H-J
authors.initials: HJ
authors.lastname: Wang
authors.forename: R M
authors.initials: RM
authors.lastname: Elashoff
authors.forename: J A
authors.initials: JA
authors.lastname: Belperio
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D054367:Receptors, CXCR3 / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000150:complications* / Q000378:metabolism / Q000821:virology; D012307:Risk Factors; D014184:Transplantation, Homologous; D014777:Virus Diseases / Q000150:complications* / Q000378:metabolism / Q000821:virology; D014780:Viruses / Q000302:isolation & purification
chemical_list: D015415:Biomarkers; C515187:CXCR3 protein, human; D008024:Ligands; D054367:Receptors, CXCR3