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Published online before print January 8, 2008

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(Journal of Leukocyte Biology. 2008;83:1060-1067.)
© 2008 by Society for Leukocyte Biology

Stimulation of the primary anti-HIV antibody response by IFN- in patients with acute HIV-1 infection

Laura Adalid-Peralta^*,,1, Véronique Godot^*,,1, Céline Colin^,1, Roman Krzysiek^*,,, Thi Tran^*,, Pascal Poignard^||, Alain Venet^¶, Anne Hosmalin^**,, Pierre Lebon, Christine Rouzioux, Genevieve Chene, Dominique Emilie^*,,,2 the Interprim ANRS 112 Study Group³

^* INSERM U764, Clamart, France;
University Paris-Sud, Faculté de Médecine Paris-Sud, Institut Fédératif de Recherche, Clamart, France;
INSERM U593, University Victor Segalen Bordeaux 2, Institut de Santé Publique, d’Epidémiologie et de Développement, Bordeaux, France;
Assistance Publique-Hôpitaux de Paris, Hôpital Antoine Béclère, Service de Microbiologie-Immunologie Biologique, Clamart, France;
^|| Centre d’Immunologie de Marseille-Luminy, INSERM, Centre National de la Recherche Scientifique, University de la Méditerranée, France;
^¶ INSERM U822, Le Kremlin Bicêtre, France;
^** Institut Cochin, Département d’Immunologie, University Paris Descartes, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France;
INSERM U567, Paris, France;
Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Vincent de Paul, Service de Microbiologie, Paris, France; and
Laboratoire de Virologie, CHU Necker EA 3620, University Paris-Descartes, Paris, France

² Correspondence: INSERM U764, 32 rue des Carnets F-92140, Clamart, France. E-mail: dominique.emilie{at}u-psud.fr

ABSTRACT

Type I IFNs are needed for the production of antiviral antibodies in mice; whether they also stimulate primary antibody responses in vivo during human viral infections is unknown. This was assessed in patients acutely infected with HIV-1 and treated with IFN-2b. Patients with acute HIV-1 infection were randomized to receive antiretroviral therapy alone (Group A, n=60) or combined for 14 weeks with pegylated-IFN-2b (Group B, n=30). Emergence of anti-HIV antibodies was monitored during 32 weeks by Western blot (WB) analyses of serum samples. IFN-2b treatment stimulated the production of anti-HIV antibodies. On Week 32, 19 weeks after the last IFN-2b administration, there were 8.5 (6.5–10.0) HIV WB bands (median, interquartile range) in Group B and 7.0 (5.0–10.0) bands in Group A (P=0.054), and band intensities were stronger in Group B (P<0.05 for p18, p24, p34, p40, and p55 HIV antigens). IFN-2b treatment also increased circulating concentrations of the B cell-activating factor of the TNF family (P<0.001) and ex vivo production of IL-12 (P<0.05), reflecting its effect on innate immune cells. Withdrawal of antiretroviral treatment on Week 36 resulted in a lower rebound of HIV replication in Group B than in Group A (P<0.05). Therefore, type I IFNs stimulate the emerging anti-HIV immune response in patients with acute HIV-1 infection, resulting in an improved control of HIV replication. Type I IFNs are thus critical in the development of efficient antiviral immune responses in humans, including the production of antiviral antibodies.

Key Words: B lymphocyte • dendritic cell • B cell-activating factor • BAFF protein