CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG

Clark, David A.; Wong, Karrie; Banwatt, Daljeet; Chen, Ziqhi; Liu, Jian; Lee, Lydia; Gorczynski, Reginald M.; Blajchman, Morris A.

doi:10.1007/s10815-008-9202-9

Cited by 34 publications

(28 citation statements)

References 16 publications

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“…14,15 Obviously, I am now advocating a middle ground. Notwithstanding that some patients received a type of IVIG with inferior NK-cell suppressive potency and the trial was stopped prematurely, 16,17 an important aspect in the Stephenson trial was exclusion of RCTs in which some of the patients with immunological test abnormalities (i.e. Did the patient have a condition likely to play a role in infertility or RSA, and if so, when treatment was given, did it correct the abnormality ?…”

Section: Empiricism Versus Determinism In Evidence-based Medicine: Thmentioning

confidence: 99%

The Power of Observation

Clark¹

2011

American J Rep Immunol

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Section: Empiricism Versus Determinism In Evidence-based Medicine: Thmentioning

confidence: 99%

The Power of Observation

Clark¹

2011

American J Rep Immunol

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“…This mechanism also acts in patients with antiphospholipid antibodies where IVIG work as anti-anti-PL [86][87][88]. And IVIG also reduce NK cell activity and cytotoxicity in vitro, as recently demonstrated both via CD200-dependent and non-CD200-dependent pathways [89]. This effect has been compared with prednisolone that was almost equally effective in vitro in suppressing NK cell cytolytic activity [90].…”

Section: Nk Cells and High Doses Intravenous Immunoglobulinsmentioning

confidence: 87%

NK Cells, Autoantibodies, and Immunologic Infertility: A Complex Interplay

Carolis

Perricone

2009

Clinic Rev Allerg Immunol

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Infertility and recurrent spontaneous abortion (RSA) are heterogeneous conditions that have been frequently explained with an immunological pathomechanism. A deeper insight into apparently unexplained infertility and RSA shows increasing evidences supporting both alloimmune and autoimmune mechanisms, in which natural killer (NK) cells and autoantibodies seem to play a relevant role. Successful pregnancy is considered as Th1-Th2 cooperation phenomenon, with a predominantly Th2-type lymphocytes response, together with the emerging role of interleukin (IL)-12, IL-15, and IL-18 and of other unidentified soluble factors dependent on NK cells. Uterine NK cells comprise the largest population at implantation site, and their activity, characteristics, and abundance suggest that they participate at the "decidualization" process that, vice versa, induces NK activation and recruitment in each menstrual cycle. However, NK cell alteration may be associated with impaired pregnancy, and the modulation in the number of circulating NK cells is most likely to be a primary event rather than an active inflammation/drug administration consequence during an inflammatory/autoimmune process, thus playing an important role in the pathogenesis of immunological infertility. Relationships within immunological infertility, recurrent spontaneous abortion, autoantibodies, and NK cells will be reviewed herein.

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“…The Fab, F(ab') 2 or Fc fragments of IVIg proved inactive compared to intact IVIg (Fig. 1B), possibly because generating IgG fragments may not preserve non-covalently associated anti-abortive soluble CD200 [19]. Few reports on the chronology of abortion are available, although several studies reported on various events of abortion using the uRPL mouse model, such as time of onset [50,51], decreased P4 levels [30], or increased uNK cell numbers [23].…”

Section: Discussionmentioning

confidence: 99%

“…The proposed mechanisms of IVIg action in autoimmune diseases involve the modulation of Fc receptors, interference with the cytokine network and complements, provision of anti-idiotypic antibodies, suppression of lymphocyte effector function [14,16,17], presentation of regulatory T cell-inducing epitope termed "Tregitope" [18], and "sialylated IgG" that indirectly upregulates the inhibitory IgG Fc receptor FcγRIIB on effector macrophages [15]. Clark et al reported that in the case of abortion, soluble CD200 molecule containing IVIg suppresses the cytotoxic activity of peripheral NK cells [19]. Although these studies show the increased research interest in the role of IVIg for autoimmune disease treatment during the last decade, the precise mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Intravenous Immunoglobulin Suppresses Abortion Relates to an Increase in the CD44bright NK Subset in Recurrent Pregnancy Loss Model Mice

Tanaka¹,

Kitashoji²,

Fukunaga³

et al. 2016

Biology of Reproduction

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Recurrent pregnancy loss (RPL), which mostly is of unknown etiology (unexplained RPL, uRPL), is defined as three or more consecutive spontaneous abortions. Some women with uRPL display a higher fraction and cytotoxicity of natural killer (NK) cells in the periphery and endometrium. Therefore, some uRPL cases have been explained by autoimmune abnormalities. The efficacy of intravenous immunoglobulin (IVIg) for uRPL has been confirmed in several clinical trials; however, its mechanism remains unknown, mainly because the abortion mechanism remains to be elucidated. In the present study, we analyzed the mechanisms of both abortion and IVIg action using a uRPL mouse model in which abortion was induced by lipopolysaccharide injection. IVIg attenuated the abortion rate in the uRPL model mice. The suppressive effect of IVIg was maximized by high dose administration early after lipopolysaccharide injection. Specifically, we discovered the presence of two distinct uterine NK (uNK) subsets: CD44(bright) and CD44(mid) In uRPL model mice, we observed an increase in the number of CD44(bright) uNK cells, while the CD44(mid) uNK subset remained unchanged. Furthermore, when abortion was reduced by IVIg administration, the cell number of the CD44(bright) uNK subset did not increase, which might allow differentiating pathological from normal uNK cells based on CD44 expression. Based on these results, we propose not only an effective administration protocol of IVIg to the uRPL model mice, but also a novel mechanism of abortion related to the increase in the CD44(bright) subset and of IVIg, which suppresses the increase of the CD44(bright) subset.

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CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG

Cited by 34 publications

References 16 publications

The Power of Observation

The Power of Observation

NK Cells, Autoantibodies, and Immunologic Infertility: A Complex Interplay

Intravenous Immunoglobulin Suppresses Abortion Relates to an Increase in the CD44bright NK Subset in Recurrent Pregnancy Loss Model Mice

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