title: Antibody markers of incident tuberculosis among HIV-infected adults in the USA: a historical prospective study.
abstract: OBJECTIVE
  To assess whether serum levels of antibodies against Mycobacterium tuberculosis antigens increase before diagnosis of active tuberculosis (TB).
  
  
  METHODS
  Serial serum samples were obtained from 30 human immunodeficiency virus (HIV) co-infected individuals who developed active TB during a multicenter prospective study on pulmonary complications of HIV/AIDS conducted among >1300 subjects in the USA in the 1980s. Multiple serum samples from 47 matched control individuals who did not develop TB in the same study were also tested. Immunoglobulin G (IgG) antibodies to 10 M. tuberculosis proteins were detected by enzyme-linked immunosorbent assay (ELISA), and data were analyzed by descriptive and inferential statistical techniques to assess patterns, trends and differences in antibody levels relative to time from TB diagnosis.
  
  
  RESULTS
  Antibodies to five antigens (ESAT-6, 38 kDa Ag, 16 kDa Ag, malate synthase and MTSA-10/CFP-10), but not to five other antigens (Rv2626c, ferredoxin A, glutamine synthetase, alanine dehydrogenase and Ag85) increased before diagnosis of TB relative to control levels. The earliest increase in the TB group was detected for MTSA-10/CFP-10 (24-30 months pre-diagnosis).
  
  
  CONCLUSIONS
  Levels of serum antibodies to particular proteins of M. tuberculosis increase before microbiological and clinical symptoms of active TB. The use of antibody biomarkers for prognostic purposes should therefore be feasible.
authors.affiliation: Public Health Research Institute Center, New Jersey Medical School, Newark, NJ 07103, USA. gennaro@phri.org
authors.forename: M L
authors.initials: ML
authors.lastname: Gennaro
authors.forename: M
authors.initials: M
authors.lastname: Affouf
authors.forename: G V
authors.initials: GV
authors.lastname: Kanaujia
authors.forename: P N
authors.initials: PN
authors.lastname: Brusasca
authors.forename: B
authors.initials: B
authors.lastname: Mangura
authors.forename: L
authors.initials: L
authors.lastname: Reichman
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005240:Feasibility Studies; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D015994:Incidence; D008074:Lipoproteins / Q000276:immunology; D008292:Malate Synthase / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D014481:United States / Q000453:epidemiology
chemical_list: C075966:Ag38 antigen, Mycobacterium tuberculosis; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D008074:Lipoproteins; C072681:Mycobacterium tuberculosis antigens; D008292:Malate Synthase