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 D.
AU - Sereti, Irini
N1 - Funding Information:
The authors thank the study participants, referring physicians, and the clinical staff of Outpatient Clinic 8 at the National Institutes of Health and acknowledge Catherine Rehm and Sara Jones for logistical support, Sonya Krishnan for sample processing, Maura Manion and Elizabeth Richards for performing additional assays of T-cell function, and the National Institute of Allergy and Infectious Diseases Data Safety Monitoring Board and Institutional Review Board. This work was supported in whole or in part by the intramural research programs of the National Institute of Allergy and Infectious Diseases, the National Institute of Dental and Craniofacial Research, an intramural Bench-to-Bedside grant from the National Institutes of Health (NIH), and by federal funding from the National Cancer Institute, NIH, under Contract No. HHSN261200800001E.
Publisher Copyright:
Copyright 2011 by The American Society of Hematology; All rights reserved.
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.
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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 -