CD40 agonist antibody mediated improvement of chronic Cryptosporidium infection in patients with X-linked hyper IgM syndrome

被引：17

作者：

Fan, Xiying ^{[1
]}

Upadhyaya, Bhaskar ^{[2
]}

Wu, Liming ^{[1
]}

Koh, Christopher ^{[4
]}

Santin-Duran, Monica ^{[9
]}

Pittaluga, Stefania ^{[6
]}

Uzel, Gulbu ^{[3
]}

Kleiner, David ^{[6
]}

Williams, Ester ^{[5
]}

Ma, Chi A. ^{[1
]}

Bodansky, Aaron ^{[1
]}

Oliveira, Joao B. ^{[5
]}

Edmonds, Pamela ^{[1
]}

Hornung, Ronald ^{[8
]}

Wong, Duane W. ^{[7
]}

Fayer, Ronald ^{[9
]}

Fleisher, Tom ^{[5
]}

Heller, Theo ^{[4
]}

Prussin, Calman ^{[2
]}

Jain, Ashish ^{[1
]}

机构：

[1] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA

[2] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA

[3] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA

[4] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA

[5] NIH, Dept Lab Med, Bethesda, MD 20892 USA

[6] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA

[7] Arizona Allergy Associates, Phoenix, AZ USA

[8] NCI, SAIC Frederick Inc, Clin Serv Program, Frederick, MD 21701 USA

[9] USDA, Environm Microbial & Food Safety Lab, Beltsville, MD 20705 USA

来源：

CLINICAL IMMUNOLOGY | 2012年 / 143卷 / 02期

基金：

美国国家卫生研究院;

关键词：

X-linked hyper-IgM syndrome; CD40; ligand; CP-870,893; CD40-R internalization; DENDRITIC CELLS; CD40-CD40L INTERACTIONS; IMMUNOLOGICAL FEATURES; T-CELLS; PHASE-I; LIGAND; MICE; ACTIVATION; IMMUNODEFICIENCY; DEFICIENCY;

D O I：

10.1016/j.clim.2012.01.014

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

X-linked hyper-IgM syndrome (XHM) is a combined immune deficiency disorder caused by mutations in CD40 ligand. We tested CP-870,893, a human CD40 agonist monoclonal antibody, in the treatment of two XHM patients with biliary Cryptosporidiosis. CP-870,893 activated B cells and APCs in vitro, restoring class switch recombination in XHM B cells and inducing cytokine secretion by monocytes. CP-870,893 infusions were well tolerated and showed significant activity in vivo, decreasing leukocyte concentration in peripheral blood. Although specific antibody responses were lacking, frequent dosing in one subject primed T cells to secrete IFN-g and suppressed oocyst shedding in the stool. Nevertheless, relapse occurred after discontinuation of therapy. The CD40 receptor was rapidly internalized following binding with CP-870,893, potentially explaining the limited capacity of CP-870,893 to mediate immune reconstitution. This study demonstrates that CP-870,893 suppressed oocysts shedding in XHM patients with biliary cryptosporidiosis. The continued study of CD40 agonists in XHM is warranted. Published by Elsevier Inc.

引用

页码：152 / 161

页数：10

共 38 条

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