title: Macrophage inflammatory protein-1alpha: a salivary biomarker of bone loss in a longitudinal cohort study of children at risk for aggressive periodontal disease?
abstract: BACKGROUND
  Periodontitis develops in a time-dependent manner. Cross-sectional studies document one moment in time but fail to capture the progressive nature of disease. Radiographic measures of bone loss are relatively insensitive but are reliable markers of irreversible disease. Longitudinal studies are needed to identify biomarkers that can precede radiographic evidence of bone loss and, thus, mark the period prior to clinical evidence of irreversible disease. A longitudinal study of students susceptible to localized aggressive periodontitis (LAgP) was conducted to evaluate chemokines/cytokines found in saliva derived from periodontally healthy children who subsequently developed alveolar bone loss.
  
  
  METHODS
  Students were screened, sampled for Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans [Aa]), and divided into a cohort of Aa+ and Aa- students. Ninety-six periodontally healthy Aa+ and Aa- students were recalled every 6 to 9 months following screening. Examinations, saliva collections, and radiographs were performed. After seven students developed bone loss, the levels of 21 cytokines were assessed and matched to saliva from seven Aa+ and seven Aa- students who remained healthy for > or =1 year. Subsequently, saliva from an additional 27 students who remained healthy was analyzed.
  
  
  RESULTS
  Nineteen cytokines were not detected or were detected at low levels. Macrophage inflammatory protein (MIP)-1alpha was elevated 50-fold in seven Aa+ students who developed disease 6 to 9 months prior to radiographic detection of bone loss compared to levels in 21 Aa+ and 20 Aa- students who remained healthy (P <0.001). Interleukin (IL)-1beta was also elevated (P = 0.01). MIP-1alpha had a specificity of 96.8% and a sensitivity of 100%, whereas IL-1beta showed 90.3% specificity and 85.7% sensitivity relative to bone loss. MIP-1alpha levels were also related to increasing probing depth and the number of pockets >6 mm.
  
  
  CONCLUSIONS
  The superior sensitivity and specificity of MIP-1alpha, which correlated well with probing depths and the onset of bone loss, suggested that it could be used as an early biomarker for LAgP.
authors.affiliation: Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fine
authors.forename: Kenneth
authors.initials: K
authors.lastname: Markowitz
authors.forename: David
authors.initials: D
authors.lastname: Furgang
authors.forename: Karen
authors.initials: K
authors.lastname: Fairlie
authors.forename: Javier
authors.initials: J
authors.lastname: Ferrandiz
authors.forename: Cebile
authors.initials: C
authors.lastname: Nasri
authors.forename: Marie
authors.initials: M
authors.lastname: McKiernan
authors.forename: Robert
authors.initials: R
authors.lastname: Donnelly
authors.forename: John
authors.initials: J
authors.lastname: Gunsolley
mesh_terms: D000293:Adolescent; D016976:Aggregatibacter actinomycetemcomitans / Q000302:isolation & purification; D010520:Aggressive Periodontitis / Q000276:immunology* / Q000382:microbiology; D016301:Alveolar Bone Loss / Q000276:immunology* / Q000382:microbiology; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D054405:Chemokine CCL3 / Q000032:analysis*; D002648:Child; D015331:Cohort Studies; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000032:analysis; D008137:Longitudinal Studies; D008297:Male; D017622:Periodontal Attachment Loss / Q000276:immunology / Q000382:microbiology; D010514:Periodontal Pocket / Q000276:immunology / Q000382:microbiology; D010519:Periodontium / Q000382:microbiology; D012307:Risk Factors; D012463:Saliva / Q000276:immunology* / Q000382:microbiology; D012471:Salivary Proteins and Peptides / Q000032:analysis*; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D054405:Chemokine CCL3; D053583:Interleukin-1beta; D012471:Salivary Proteins and Peptides