title: Anti-phospholipid antibody levels as biomarker for monitoring tuberculosis treatment response.
abstract: Standard methods to monitor tuberculosis (TB) treatment response rely on sputum microscopy and culture conversion. Alternatives to these methods are needed for those patients whose sputum tests are smear or culture negative. Here, we examine anti-phospholipid IgM antibody level changes as a biomarker for treatment response in smear positive TB patients. Serum samples were obtained from 40 pulmonary TB patients at the start and end of the intensive phase treatment (IPT) from the CDC-TB Trials Consortium randomized clinical trial in Kampala, Uganda. Samples were screened by ELISA for IgM levels against five phospholipids found in Mycobacterium tuberculosis and host cells. Lipid antigens included cardiolipin (CL), phosphatidyl inositol (PI), phosphatidyl ethanolamine (PE), phosphatidyl choline (PTC), and sphingolipid (SL). Levels of IgM against all phospholipids significantly decreased (p = 0.034, 0.001, 0.008 0.008, 0.040, respectively) following anti-TB drug treatment in patients without lung cavitary disease at baseline. The mean sensitivity of this test in these patients was 83% when the IgM response to a single lipid antigen was used; it was >90% when responses to 2 or more lipids were assessed. In contrast, cavitary TB patients showed an overall IgM increase, with a significant rise against PE (p = 0.025). There was no significant difference in the change in antibody levels between patients who remained culture-positive and those who culture-converted after 40 doses of drug therapy. The measurement of IgM anti-phospholipid antibodies may be a useful biomarker to monitor treatment response in non-cavitary TB patients.
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, 201 Hildebrand Hall, University of California, Berkeley, CA 94720, USA. agoodridge@cal.berkeley.edu
authors.forename: Amador
authors.initials: A
authors.lastname: Goodridge
authors.forename: Carla
authors.initials: C
authors.lastname: Cueva
authors.forename: Maureen
authors.initials: M
authors.lastname: Lahiff
authors.forename: Grace
authors.initials: G
authors.lastname: Muzanye
authors.forename: John L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Payam
authors.initials: P
authors.lastname: Nahid
authors.forename: Lee W
authors.initials: LW
authors.lastname: Riley
mesh_terms: D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016903:Drug Monitoring / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology; D055815:Young Adult
chemical_list: D017152:Antibodies, Antiphospholipid; D000995:Antitubercular Agents; D015415:Biomarkers; D007075:Immunoglobulin M