Anti-PGL-Tb1 responses as an indicator of the immune restoration syndrome in HIV-TB patients - 23/08/11

Doi : 10.1016/j.tube.2008.01.006

N. Simonney ^a,^{^{i
Both authors contributed equally to this work.}}, G. Dewulf ^a,^{^{i
Both authors contributed equally to this work.}}, J.-L. Herrmann ^a,^⁎ , M.C. Gutierrez ^b, E. Vicaut ^c, C. Boutron ^c, M. Leportier ^d, M. Lafaurie ^e, S. Abgrall ^f, D. Sereni ^g, B. Autran ^h, G. Carcelain ^h, A. Bourgarit ^g,^h, P.H. Lagrange ^a,^⁎
^a EA3510, UFR Denis Diderot, Université Paris VII et Service de Microbiologie, Hôpital Saint-Louis, Assistance Publique—Hôpitaux de Paris, CIB HOG, Paris, France
^b Unité Biodiversité des Bactéries Pathogènes Emergentes, Institut Pasteur, Paris, France
^c Unité de Recherche Clinique, Hôpital Fernand Widal, Assistance Publique—Hôpitaux de Paris, Paris, France
^d R&D Department, Bio Mérieux, Marcy l'Etoile, France
^e Service de Maladies Infectieuses, Hôpital Saint-Louis, Assistance Publique—Hôpitaux de Paris, Paris, France
^f Service de Maladies Infectieuses, Avicenne Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France
^g Internal Medicine Department, Saint-Louis Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France
^h Laboratoire d'Immunologie Cellulaire, INSERM U 543, Pitié-Salpêtrière Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France

Corresponding author. Service de Microbiologie, Hôpital Raymond Poincaré, 104 Bd Raymond Poincaré, 92380 Garches, France. Tel.: +33 (0)1 47 10 79 50; fax: +33 (0)1 47 10 79 49.Corresponding author. Service de Microbiologie, Hôpital Saint Louis, 1 avenue Claude Vellefaux, 75475 Paris, France. Tel.: +33 (0)1 42 38 53 79; fax: +33 (0)1 42 49 92 00.

Summary

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.

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Keywords : Immune restoration syndrome, HIV, Tuberculosis, Anti-PGL-Tb1 antibody, Strain typing

Plan

Introduction

Materials and methods

Patients

Clinical isolates

ELISA assay

Detection of TB specific circulating B cells

Statistical analysis

Results

Discussion

This work was presented as an invited guest lecture at the International Conference on Opportunistic pathogens in AIDS & 3rd National Conference of Laboratory Medicine. AIIMS, New Delhi. 27–29 March 2006.

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Vol 88 - N° 5

P. 453-461 - septembre 2008 Retour au numéro

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Anti-PGL-Tb1 responses as an indicator of the immune restoration syndrome in HIV-TB patients - 23/08/11

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