title: Extracellular cyclophilin levels associate with parameters of asthma in phenotypic clusters.
abstract: OBJECTIVE
  Leukocyte persistence during chronic (quiescent) phases of asthma is a major hallmark of the disease. The mechanisms regulating these persistent leukocyte populations are not clearly understood. An alternative family of chemoattracting proteins, cyclophilins (Cyps), has recently been shown to contribute to leukocyte recruitment in animal models of allergic asthma. The goals of this study were to determine whether Cyps are present in asthma patients during the chronic phase of the disease and to investigate whether levels of Cyps associate with clinical parameters of disease severity.
  
  
  METHODS
  Nasal wash samples from an urban cohort of 137 patients of age 6-20 years with physician-diagnosed asthma were examined for the presence of cyclophilin A (CypA), cyclophilin B (CypB), as well as several other classical chemokines. Linear, logistic, or ordinal regressions were performed to identify associations between Cyps, chemokines, and clinical parameters of asthma. The asthma cohort was further divided into previously established phenotypic clusters (cluster 1: n = 55; cluster 2: n = 31; and cluster 3: n = 51) and examined for associations.
  
  
  RESULTS
  Levels of CypB in the asthma group were highly elevated compared to nonasthmatic controls, while a slight increase in Monocyte Chemotactic Protein-1 (MCP-1) was also observed. CypA and MCP-1 were associated with levels of eosinophil cationic protein (ECP; a marker of eosinophil activation). Cluster-specific associations were found for CypA and CypB and clinical asthma parameters [e.g. forced expiratory volume in 1 second (FEV(1)) and ECP].
  
  
  CONCLUSIONS
  Cyps are present in nasal wash samples of asthma patients and may be a novel biomarker for clinical parameters of asthma severity.
authors: Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University Medical Center, Washington D.C., USA.
authors: Erik J
authors: EJ
authors: Stemmy
authors: Center for Genetic Medicine Research, Children's National Medical Center, Washington D.C., USA.
authors: Angela S
authors: AS
authors: Benton
authors: Center for Genetic Medicine Research, Children's National Medical Center, Washington D.C., USA.
authors: Jennifer
authors: J
authors: Lerner
authors: Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University Medical Center, Washington D.C., USA.
authors: Sarah
authors: S
authors: Alcala
authors: Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University Medical Center, Washington D.C., USA.
authors: Stephanie L
authors: SL
authors: Constant
authors: Center for Genetic Medicine Research, Children's National Medical Center, Washington D.C., USA.|Departments of Pediatrics, Emergency Medicine, and Integrative Systems Biology, The George Washington University Medical Center, Washington D.C., USA.
authors: Robert J
authors: RJ
authors: Freishtat
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D018932:Chemokine CCL2 / Q000032:analysis; D018925:Chemokines / Q000032:analysis; D002648:Child; D021983:Cyclophilins / Q000032:analysis*; D047150:Eosinophil Cationic Protein / Q000032:analysis; D005110:Extracellular Space / Q000737:chemistry; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D017817:Nasal Lavage Fluid / Q000737:chemistry; D010641:Phenotype; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D018925:Chemokines; D047150:Eosinophil Cationic Protein; D021983:Cyclophilins