Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia

Virginia Sheikh, Brian O. Porter, Rebecca DerSimonian, Stephen B. Kovacs, William L. Thompson, Ainhoa Perez-Diez, Alexandra F. Freeman, Gregg Roby, Joann Mican, Alice Pau, Adam Rupert, Joseph Adelsberger, Jeanette Higgins, Jeffrey S. Bourgeois, Stig M.R. Jensen, David R. Morcock, Peter D. Burbelo, Leah Osnos, Irina Maric, Ven NatarajanTherese Croughs, Michael D. Yao, Jacob Estes, Irini Sereti

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Idiopathic CD4 lymphopenia (ICL) is a rare syndrome defined by low CD4 T-cell counts (<300/mL) without evidence of HIV infection or other known cause of immunodeficiency. ICL confers an increased risk of opportunistic infections and has no established treatment. Interleukin-7 (IL-7) is fundamental for thymopoiesis, T-cell homeostasis, and survival of mature T cells, which provides a rationale for its potential use as an immunotherapeutic agent for ICL. We performed an open-label phase 1/2A doseescalation trial of 3 subcutaneous doses of recombinant human IL-7 (rhIL-7) per week in patients with ICL who were at risk of disease progression. The primary objectives of the study were to assess safety and the immunomodulatory effects of rhIL-7 in ICL patients. Injection site reactions were the most frequently reported adverse events. One patient experienced a hypersensitivity reaction and developed non-neutralizing anti-IL-7 antibodies. Patients with autoimmune diseases that required systemic therapy at screening were excluded from the study; however, 1 participant developed systemic lupus erythematosus while on study and was excluded from further rhIL-7 dosing. Quantitatively, rhIL-7 led to an increase in the number of circulating CD4 and CD8 T cells and tissue-resident CD3 T cells in the gut mucosa and bone marrow. Functionally, these T cells were capable of producing cytokines after mitogenic stimulation. rhIL-7 was well tolerated at biologically active doses andmay represent a promising therapeutic intervention in ICL.

Original languageEnglish (US)
Pages (from-to)977-988
Number of pages12
JournalBlood
Volume127
Issue number8
DOIs
StatePublished - Feb 25 2016
Externally publishedYes

Fingerprint

Interleukin-7
Lymphopenia
T-cells
T-Lymphocytes
Opportunistic Infections
CD4 Lymphocyte Count
Systemic Lupus Erythematosus
Autoimmune Diseases
HIV Infections
Disease Progression
Labels
Cell Survival
Screening
Hypersensitivity
Bone
Mucous Membrane
Homeostasis
Therapeutics
Bone Marrow
Tissue

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Sheikh, V., Porter, B. O., DerSimonian, R., Kovacs, S. B., Thompson, W. L., Perez-Diez, A., ... Sereti, I. (2016). Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia. Blood, 127(8), 977-988. https://doi.org/10.1182/blood-2015-05-645077

Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia. / Sheikh, Virginia; Porter, Brian O.; DerSimonian, Rebecca; Kovacs, Stephen B.; Thompson, William L.; Perez-Diez, Ainhoa; Freeman, Alexandra F.; Roby, Gregg; Mican, Joann; Pau, Alice; Rupert, Adam; Adelsberger, Joseph; Higgins, Jeanette; Bourgeois, Jeffrey S.; Jensen, Stig M.R.; Morcock, David R.; Burbelo, Peter D.; Osnos, Leah; Maric, Irina; Natarajan, Ven; Croughs, Therese; Yao, Michael D.; Estes, Jacob; Sereti, Irini.

In: Blood, Vol. 127, No. 8, 25.02.2016, p. 977-988.

Research output: Contribution to journalArticle

Sheikh, V, Porter, BO, DerSimonian, R, Kovacs, SB, Thompson, WL, Perez-Diez, A, Freeman, AF, Roby, G, Mican, J, Pau, A, Rupert, A, Adelsberger, J, Higgins, J, Bourgeois, JS, Jensen, SMR, Morcock, DR, Burbelo, PD, Osnos, L, Maric, I, Natarajan, V, Croughs, T, Yao, MD, Estes, J & Sereti, I 2016, 'Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia', Blood, vol. 127, no. 8, pp. 977-988. https://doi.org/10.1182/blood-2015-05-645077
Sheikh V, Porter BO, DerSimonian R, Kovacs SB, Thompson WL, Perez-Diez A et al. Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia. Blood. 2016 Feb 25;127(8):977-988. https://doi.org/10.1182/blood-2015-05-645077
Sheikh, Virginia ; Porter, Brian O. ; DerSimonian, Rebecca ; Kovacs, Stephen B. ; Thompson, William L. ; Perez-Diez, Ainhoa ; Freeman, Alexandra F. ; Roby, Gregg ; Mican, Joann ; Pau, Alice ; Rupert, Adam ; Adelsberger, Joseph ; Higgins, Jeanette ; Bourgeois, Jeffrey S. ; Jensen, Stig M.R. ; Morcock, David R. ; Burbelo, Peter D. ; Osnos, Leah ; Maric, Irina ; Natarajan, Ven ; Croughs, Therese ; Yao, Michael D. ; Estes, Jacob ; Sereti, Irini. / Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia. In: Blood. 2016 ; Vol. 127, No. 8. pp. 977-988.
@article{02f00f2cad924042a4387ae108324630,
title = "Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia",
abstract = "Idiopathic CD4 lymphopenia (ICL) is a rare syndrome defined by low CD4 T-cell counts (<300/mL) without evidence of HIV infection or other known cause of immunodeficiency. ICL confers an increased risk of opportunistic infections and has no established treatment. Interleukin-7 (IL-7) is fundamental for thymopoiesis, T-cell homeostasis, and survival of mature T cells, which provides a rationale for its potential use as an immunotherapeutic agent for ICL. We performed an open-label phase 1/2A doseescalation trial of 3 subcutaneous doses of recombinant human IL-7 (rhIL-7) per week in patients with ICL who were at risk of disease progression. The primary objectives of the study were to assess safety and the immunomodulatory effects of rhIL-7 in ICL patients. Injection site reactions were the most frequently reported adverse events. One patient experienced a hypersensitivity reaction and developed non-neutralizing anti-IL-7 antibodies. Patients with autoimmune diseases that required systemic therapy at screening were excluded from the study; however, 1 participant developed systemic lupus erythematosus while on study and was excluded from further rhIL-7 dosing. Quantitatively, rhIL-7 led to an increase in the number of circulating CD4 and CD8 T cells and tissue-resident CD3 T cells in the gut mucosa and bone marrow. Functionally, these T cells were capable of producing cytokines after mitogenic stimulation. rhIL-7 was well tolerated at biologically active doses andmay represent a promising therapeutic intervention in ICL.",
author = "Virginia Sheikh and Porter, {Brian O.} and Rebecca DerSimonian and Kovacs, {Stephen B.} and Thompson, {William L.} and Ainhoa Perez-Diez and Freeman, {Alexandra F.} and Gregg Roby and Joann Mican and Alice Pau and Adam Rupert and Joseph Adelsberger and Jeanette Higgins and Bourgeois, {Jeffrey S.} and Jensen, {Stig M.R.} and Morcock, {David R.} and Burbelo, {Peter D.} and Leah Osnos and Irina Maric and Ven Natarajan and Therese Croughs and Yao, {Michael D.} and Jacob Estes and Irini Sereti",
year = "2016",
month = "2",
day = "25",
doi = "10.1182/blood-2015-05-645077",
language = "English (US)",
volume = "127",
pages = "977--988",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "8",

}

TY - JOUR

T1 - Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia

AU - Sheikh, Virginia

AU - Porter, Brian O.

AU - DerSimonian, Rebecca

AU - Kovacs, Stephen B.

AU - Thompson, William L.

AU - Perez-Diez, Ainhoa

AU - Freeman, Alexandra F.

AU - Roby, Gregg

AU - Mican, Joann

AU - Pau, Alice

AU - Rupert, Adam

AU - Adelsberger, Joseph

AU - Higgins, Jeanette

AU - Bourgeois, Jeffrey S.

AU - Jensen, Stig M.R.

AU - Morcock, David R.

AU - Burbelo, Peter D.

AU - Osnos, Leah

AU - Maric, Irina

AU - Natarajan, Ven

AU - Croughs, Therese

AU - Yao, Michael D.

AU - Estes, Jacob

AU - Sereti, Irini

PY - 2016/2/25

Y1 - 2016/2/25

N2 - Idiopathic CD4 lymphopenia (ICL) is a rare syndrome defined by low CD4 T-cell counts (<300/mL) without evidence of HIV infection or other known cause of immunodeficiency. ICL confers an increased risk of opportunistic infections and has no established treatment. Interleukin-7 (IL-7) is fundamental for thymopoiesis, T-cell homeostasis, and survival of mature T cells, which provides a rationale for its potential use as an immunotherapeutic agent for ICL. We performed an open-label phase 1/2A doseescalation trial of 3 subcutaneous doses of recombinant human IL-7 (rhIL-7) per week in patients with ICL who were at risk of disease progression. The primary objectives of the study were to assess safety and the immunomodulatory effects of rhIL-7 in ICL patients. Injection site reactions were the most frequently reported adverse events. One patient experienced a hypersensitivity reaction and developed non-neutralizing anti-IL-7 antibodies. Patients with autoimmune diseases that required systemic therapy at screening were excluded from the study; however, 1 participant developed systemic lupus erythematosus while on study and was excluded from further rhIL-7 dosing. Quantitatively, rhIL-7 led to an increase in the number of circulating CD4 and CD8 T cells and tissue-resident CD3 T cells in the gut mucosa and bone marrow. Functionally, these T cells were capable of producing cytokines after mitogenic stimulation. rhIL-7 was well tolerated at biologically active doses andmay represent a promising therapeutic intervention in ICL.

AB - Idiopathic CD4 lymphopenia (ICL) is a rare syndrome defined by low CD4 T-cell counts (<300/mL) without evidence of HIV infection or other known cause of immunodeficiency. ICL confers an increased risk of opportunistic infections and has no established treatment. Interleukin-7 (IL-7) is fundamental for thymopoiesis, T-cell homeostasis, and survival of mature T cells, which provides a rationale for its potential use as an immunotherapeutic agent for ICL. We performed an open-label phase 1/2A doseescalation trial of 3 subcutaneous doses of recombinant human IL-7 (rhIL-7) per week in patients with ICL who were at risk of disease progression. The primary objectives of the study were to assess safety and the immunomodulatory effects of rhIL-7 in ICL patients. Injection site reactions were the most frequently reported adverse events. One patient experienced a hypersensitivity reaction and developed non-neutralizing anti-IL-7 antibodies. Patients with autoimmune diseases that required systemic therapy at screening were excluded from the study; however, 1 participant developed systemic lupus erythematosus while on study and was excluded from further rhIL-7 dosing. Quantitatively, rhIL-7 led to an increase in the number of circulating CD4 and CD8 T cells and tissue-resident CD3 T cells in the gut mucosa and bone marrow. Functionally, these T cells were capable of producing cytokines after mitogenic stimulation. rhIL-7 was well tolerated at biologically active doses andmay represent a promising therapeutic intervention in ICL.

UR - http://www.scopus.com/inward/record.url?scp=84960414465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960414465&partnerID=8YFLogxK

U2 - 10.1182/blood-2015-05-645077

DO - 10.1182/blood-2015-05-645077

M3 - Article

C2 - 26675348

AN - SCOPUS:84960414465

VL - 127

SP - 977

EP - 988

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -