Amelioration of murine immune thrombocytopenia by CD44 antibodies: a potential therapy for ITP?

被引：22

作者：

Crow, Andrew R. ^{[1
,2
,3
,4
]}

Song, Seng ^{[2
,3
,4
]}

Suppa, Sara J. ^{[2
,3
,4
]}

Ma, Shuhua ^{[2
,3
,4
]}

Reilly, Michael P. ^{[5
]}

Andre, Pierrette ^{[5
]}

McKenzie, Steven E. ^{[5
]}

Lazarus, Alan H. ^{[1
,2
,3
,4
,6
]}

机构：

[1] Canadian Blood Serv, Toronto, ON, Canada

[2] Li Ka Shing Knowledge Inst St Michaels, Dept Lab Med, Toronto, ON, Canada

[3] Li Ka Shing Knowledge Inst St Michaels, Keenan Res Ctr, Toronto, ON, Canada

[4] Toronto Platelet Immunobiol Grp, Toronto, ON, Canada

[5] Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA

[6] Univ Toronto, Dept Med, Toronto, ON, Canada

来源：

BLOOD | 2011年 / 117卷 / 03期

基金：

加拿大健康研究院;

关键词：

ANTIINFLAMMATORY ACTIVITY; MONOCLONAL-ANTIBODIES; INDUCED ARTHRITIS; IMMUNOGLOBULIN-G; DENDRITIC CELLS; FC-RECEPTOR; MOUSE MODEL; IVIG; INVOLVEMENT; INDUCTION;

D O I：

10.1182/blood-2010-05-280115

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

To explore the potential for monoclonal antibodies as a treatment for immune thrombocytopenia (ITP) and to further explore their mechanisms of action, we tested 8 monoclonal CD44 antibodies in murine ITP and found 4 antibodies that could successfully ameliorate ITP; 2 of these antibodies function at a full 3-log fold lower dosage compared with IVIg. Further characterization of the 2 most successful antibodies (5035-41.1D and KM114) demonstrated that, similar to IVIg: (1) the presence of the inhibitory IgG receptor Fc gamma RIIB was required for their ameliorative function, (2) complement-deficient mice responded to anti-CD44 treatment, and (3) human transgenic Fc gamma RIIA-expressing mice also responded to the CD44 therapeutic modality. Dissimilar to IVIg, the Fc portion of the CD44 antibody was not required. These data demonstrate that CD44 antibodies can function therapeutically in murine ITP and that they could potentially provide a verylow-dose recombinant therapy for the amelioration of human ITP. (Blood. 2011; 117(3): 971-974)

引用

页码：971 / 974

页数：4

共 50 条

[1] Amelioration of Murine Immune Thrombocytopenia by CD44 Antibodies: a Potential Therapy for ITP?.
Crow, Andrew R.
Song, Seng
Suppe, Sara J.
Lazarus, Alan H.
[J]. BLOOD, 2010, 116 (21) : 1048 - 1048
[2] CD44 Antibodies and Immune Thrombocytopenia in the Amelioration of Murine Inflammatory Arthritis
Mott, Patrick J.
Lazarus, Alan H.
[J]. PLOS ONE, 2013, 8 (06):
[3] Amelioration of Immune Thrombocytopenia in Human CD44 Transgenic Mice By Anti-Human CD44 Antibodies
Crow, Andrew R.
Amash, Alaa
Lazarus, Alan H.
[J]. BLOOD, 2016, 128 (22)
[4] Antibodies Against Macrophage CD44 Protect Platelets from FcγR-Mediated Phagocytosis: A Potential Mechanism for CD44 Antibody Amelioration of Murine Immune Thrombocytopenia
Norris, Peter A. A.
Wang, Yawen
Zhu, Guangheng
Wang, Lin
Huo, Ming
Fairn, Gregory D.
Ni, Heyu
Lazarus, Alan H.
[J]. BLOOD, 2017, 130
[5] CD44 antibody-mediated amelioration of murine immune thrombocytopenia (ITP): mouse background determines the effect of FcRIIb genetic disruption
Crow, Andrew R.
Amash, Alaa
Lazarus, Alan H.
[J]. TRANSFUSION, 2015, 55 (06) : 1492 - 1500
[6] Anti-inflammatory activity of CD44 antibodies in murine immune thrombocytopenia is mediated by Fcγ receptor inhibition
Norris, Peter A. A.
Kaur, Gurleen
Khan, Ramsha
Zhu, Guangheng
Ni, Heyu
Lazarus, Alan H.
[J]. BLOOD, 2021, 137 (15) : 2114 - 2124
[7] Amelioration of Murine Passive Immune Thrombocytopenia by IVIg and a Therapeutic Monoclonal CD44 Antibody Does Not Require the Myd88 Signaling Pathway
Crow, Andrew R.
Yu, Honghui
Han, Dongji
Lazarus, Alan H.
[J]. PLOS ONE, 2013, 8 (08):
[8] CD44 Antibody Mediated Amelioration of Murine ITP: Evidence for a Similar Strain Dependent FcγRIIB Requirement As Compared to Ivig
Crow, Andrew R.
Lazarus, Alan H.
[J]. BLOOD, 2012, 120 (21)
[9] Monoclonal IgG specific for the CD44 antigen mimics the action of IVIg in the amelioration of ITP.
Song, S
Crow, AR
Siragam, V
Freedman, J
Lazarus, A
[J]. BLOOD, 2005, 106 (11) : 613A - 613A
[10] Identification of variant isoforms of CD44 and their functions in murine immune cells
Guan, Hongbing
Singh, Narendra
Nagarkatti, Prakash
Nagarkatti, Mitzi
[J]. JOURNAL OF IMMUNOLOGY, 2010, 184

← 1 2 3 4 5 →