title: Interpretation of mycobacterial antibodies in the cerebrospinal fluid of adults with tuberculous meningitis.
abstract: OBJECTIVE
  Microbiological identification of Mycobacterium tuberculosis is insensitive and slow, and clinical distinction of tuberculous meningitis (TBM) from other subacute or chronic meningoenchephalitides (SACM) is difficult. Successful use of highly specific M. tuberculosis serological assays on cerebrospinal fluid has been reported, but their performance for diagnosis in a tuberculosis endemic country where they would be of most value is unclear. We sought to determine the biological basis for the uncertainty in interpretation of antibody detection in the CSF of TBM patients.
  
  
  METHODS
  We identified prospectively 46 adults with SACM and explored the concordance between TBM diagnosis and detection of highly specific M. tuberculosis antibodies in CSF. The source of antibodies in CSF was explored by evaluating the correlation between antibody titres in CSF with those in serum, or with the albumin quotient. Intrathecal IgG synthesis was assessed by the IgG index.
  
  
  RESULTS
  Positive antibody titres were more frequent among TBM patients (76%), but were also present in individuals with other SACM (59%). A positive correlation between antibody titres in CSF with those in serum, or with the albumin quotient, supported the leakage of antibodies from plasma to CSF through an increased blood-brain barrier permeability. Intrathecal IgG synthesis was only detected in 35% of the TBM cases.
  
  
  CONCLUSIONS
  Plasma antibodies likely synthesized in response to previous tuberculosis infections were a major source of mycobacterial antibodies in CSF due to leakage through an impaired blood-brain barrier. Interpretation of mycobacterial antibodies in CSF of adults for TBM, however specific, must take into account the contribution of antibodies from plasma, and hence, has questionable use for diagnosis.
authors.affiliation: Corporación para Investigaciones Biológicas, Medellín, Colombia. blanca.i.restrepo@utb.edu
authors.forename: Blanca I
authors.initials: BI
authors.lastname: Restrepo
authors.forename: Paula A
authors.initials: PA
authors.lastname: Pino
authors.forename: Michel
authors.initials: M
authors.lastname: Volcy
authors.forename: Andrés F
authors.initials: AF
authors.lastname: Franco
authors.forename: Ganga V
authors.initials: GV
authors.lastname: Kanaujia
authors.forename: Jaime
authors.initials: J
authors.lastname: Robledo
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000134:cerebrospinal fluid* / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000503:physiopathology; D003105:Colombia; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D008297:Male; D008590:Meningoencephalitis / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011446:Prospective Studies; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G