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 language | English (US) |
|---|---|
| Pages (from-to) | 977-988 |
| Number of pages | 12 |
| Journal | Blood |
| Volume | 127 |
| Issue number | 8 |
| DOIs | |
| State | Published - Feb 25 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology
Cite this
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 journal › Article
}
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 -