title: Anti-PGL-Tb1 responses as an indicator of the immune restoration syndrome in HIV-TB patients.
abstract: A prospective and multi-centre study has allowed us to analyse antibody responses and Mycobacterium tuberculosis clinical isolate genotypes on 24 consecutive HIV-TB co-infected patients treated with Highly Active Antiretroviral Therapy (HAART) who either went on to develop a TB Immune Restoration Syndrome (TB-IRS), or not. Circulating free and immune-complexed antibodies against ManLAM, ESAT-6/CFP10 and PGL-Tb1 in HIV-TB co-infected patients were measured by ELISA at the initiation of anti-TB treatment, at the date of HAART initiation and thereafter. Presence of circulating B cells was also monitored by in vitro antibody production (IVAP) against ESAT-6/CFP10 and PGL-Tb1. Finally, 16 out of 24M. tuberculosis clinical isolates from patients with TB-IRS were genotyped using spoligotyping and MIRUs-VNTR typing. Eleven patients (45.8%) experienced TB-IRS (TB-IRS+). Significantly, lower anti-PGL-Tb1 antibody levels were identified in TB-IRS+ compared to TB-IRS-negative patients prior to TB-IRS development. These very low levels were neither related to CD4 counts nor with complexed antibodies. No difference in antibody levels was observed with the other tested antigens. In addition, no specific strain genotype was associated with TB-IRS. The presence of specific anti-PGL-Tb1 antibodies only in TB-IRS-negative patients represents for the first time an indicator of a potential protective response or a diagnostic biomarker for the detection of non-progression to TB-IRS in HIV-TB co-infected patients starting HAART.
authors.affiliation: EA3510, UFR Denis Diderot, Université Paris VII et Service de Microbiologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, CIB HOG, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Simonney
authors.forename: G
authors.initials: G
authors.lastname: Dewulf
authors.forename: J-L
authors.initials: JL
authors.lastname: Herrmann
authors.forename: M C
authors.initials: MC
authors.lastname: Gutierrez
authors.forename: E
authors.initials: E
authors.lastname: Vicaut
authors.forename: C
authors.initials: C
authors.lastname: Boutron
authors.forename: M
authors.initials: M
authors.lastname: Leportier
authors.forename: M
authors.initials: M
authors.lastname: Lafaurie
authors.forename: S
authors.initials: S
authors.lastname: Abgrall
authors.forename: D
authors.initials: D
authors.lastname: Sereni
authors.forename: B
authors.initials: B
authors.lastname: Autran
authors.forename: G
authors.initials: G
authors.lastname: Carcelain
authors.forename: A
authors.initials: A
authors.lastname: Bourgarit
authors.forename: P H
authors.initials: PH
authors.lastname: Lagrange
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology*; D000328:Adult; D000942:Antigens, Bacterial / Q000096:biosynthesis*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006017:Glycolipids / Q000096:biosynthesis*; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D019562:Viral Load
chemical_list: D000942:Antigens, Bacterial; D006017:Glycolipids; C045169:phenolic glycolipid I, Mycobacterium leprae