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HIV specific B-cell memory persists in seronegative early treated children and is dominated by IgM-memory responses

Nicola Cotugno, Elena Morrocchi, Ilaria Pepponi, Salvatore Rocca, Stefania Bernardi, Stefano Rinaldi, Silvia Di Cesare, Mark J. Cameron, Suresh Pallikkuth, Paolo Rossi, Jintanat Ananworanich, Savita Pahwa and Paolo Palma
J Immunol May 1, 2018, 200 (1 Supplement) 182.34;
Nicola Cotugno
1Bambino Gesù Children’s Hospital, Rome, Italy, Italy
2University of Rome Tor Vergata, Italy
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Elena Morrocchi
2University of Rome Tor Vergata, Italy
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Ilaria Pepponi
1Bambino Gesù Children’s Hospital, Rome, Italy, Italy
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Salvatore Rocca
1Bambino Gesù Children’s Hospital, Rome, Italy, Italy
2University of Rome Tor Vergata, Italy
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Stefania Bernardi
1Bambino Gesù Children’s Hospital, Rome, Italy, Italy
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Stefano Rinaldi
3Univ. of Miami Miller Sch. of Med.
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Silvia Di Cesare
2University of Rome Tor Vergata, Italy
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Mark J. Cameron
4Case Western Reserve Univ.
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Suresh Pallikkuth
3Univ. of Miami Miller Sch. of Med.
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Paolo Rossi
1Bambino Gesù Children’s Hospital, Rome, Italy, Italy
2University of Rome Tor Vergata, Italy
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Jintanat Ananworanich
5Military HIV Research Program
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Savita Pahwa
3Univ. of Miami Miller Sch. of Med.
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Paolo Palma
1Bambino Gesù Children’s Hospital, Rome, Italy, Italy
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Abstract

Early initiation of ART in HIV vertically infected infants influences specific immunity by limiting Ag exposure and reducing the viral reservoir size. Currently these patients represent ideal candidates for testing immune therapeutic strategies towards HIV-remission. However a proportion of these early ART treated children (ET) show an undetectable HIV Ab response. It is still unknown whether such profile is associated with a lower ability of these children to mount HIV specific responses once the Ag is re-encountered.

In the present study, we investigated whether HIV specific B-cells persist in seronegative (SN) patients, and the associated gene signatures after re-encountering the virus in vitro. We enrolled 20 ET (6 SN and 14 seropositive, SP), who initiated ART at a mean age of 4.4±3.6 mo. and under durable viral control (> 2 years). We found that gp140+ B-cells, analyzed by FACS, persist in SN patients with a similar frequency of SP. Further analysis revealed a higher percentage of HIV-specific IgM cells in SN CD27+ IgD+ memory subset compared to SP (P=0.002). In addition we investigated by multiplexed RT-PCR, gene expression dynamics after in vitro stimulation with HIV peptides mix. Our results on sorted HIV specific IgM+ cells showed up-regulation of Blimp1 expression only in SP (fold change=1.9; p=0.03), suggesting an impairment of plasma cell differentiation in IgM+gp140+ B-cells in SN patients. Our results firstly reveal that HIV specific B-cell response persists in SN ET, and predominantly resides in the IgM memory compartment. We hypothesize that such responses could be targeted by novel strategies aiming at HIV remission in HIV early treated children.

  • Copyright © 2018 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 200, Issue 1 Supplement
1 May 2018
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HIV specific B-cell memory persists in seronegative early treated children and is dominated by IgM-memory responses
Nicola Cotugno, Elena Morrocchi, Ilaria Pepponi, Salvatore Rocca, Stefania Bernardi, Stefano Rinaldi, Silvia Di Cesare, Mark J. Cameron, Suresh Pallikkuth, Paolo Rossi, Jintanat Ananworanich, Savita Pahwa, Paolo Palma
The Journal of Immunology May 1, 2018, 200 (1 Supplement) 182.34;

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HIV specific B-cell memory persists in seronegative early treated children and is dominated by IgM-memory responses
Nicola Cotugno, Elena Morrocchi, Ilaria Pepponi, Salvatore Rocca, Stefania Bernardi, Stefano Rinaldi, Silvia Di Cesare, Mark J. Cameron, Suresh Pallikkuth, Paolo Rossi, Jintanat Ananworanich, Savita Pahwa, Paolo Palma
The Journal of Immunology May 1, 2018, 200 (1 Supplement) 182.34;
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