Mechanism of anti-D-mediated immune suppression – a paradox awaiting resolution?

Kumpel, Belinda M.; Elson, C. J.

doi:10.1016/s1471-4906(00)01801-9

Cited by 90 publications

(110 citation statements)

References 39 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…Presumably, epitope masking would also be fully operative in vitro, and an argument against its exclusive role is our finding that suppression in vitro is less efficient without Fc␥RIIB. In addition, some observations in the rhesus prophylaxis system are not easily explained by mere epitope masking (35). Doses of IgG anti-rhesus D, too low to cover all D Ags on human erythrocytes, suppressed the anti-D response (36).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

FcγRIIB in IgG-Mediated Suppression of Antibody Responses: Different Impact In Vivo and In Vitro

Karlsson

Getahun

Heyman

2001

The Journal of Immunology

View full text Add to dashboard Cite

The suppressive effect of IgG on Ab responses to particulate Ags such as erythrocytes is well documented. IgG-mediated suppression is used clinically in rhesus prophylaxis to prevent RhD-negative mothers from becoming immunized against their Rh D-positive fetuses. We have recently shown that IgG anti-SRBC, passively administered together with SRBC, can induce efficient suppression of primary Ab responses to SRBC in mice lacking the known FcRs for IgG (FcγRI, FcγIII, and FcγRIIB or the neonatal FcR). The lack of a demonstrable effect of the inhibitory FcγRIIB was particularly surprising, and, in this study, the involvement of this receptor is further investigated during broader experimental conditions. The data show that SRBC-specific IgG administered up to 5 days after SRBC can induce suppression both in wild-type and FcγRIIB-deficient mice. Suppression of secondary Ab responses to SRBC in vivo was similar in the two strains. In contrast, IgG-mediated suppression of Ab responses in vitro was impaired in cultures with primed FcγRIIB-deficient spleen cells. In conclusion, inhibition of in vivo Ab responses to SRBC by passively administered IgG can take place via an FcγRIIB-independent pathway. This pathway causes >99% suppression and operates during all experimental conditions studied so far. The nature of the mechanism can at present only be hypothesized. Masking of epitopes and/or rapid elimination of IgG-Ag complexes would both be compatible with the observations.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Complementmediated effects also appear unlikely because IgG, unable to activate C, is still able to suppress (30). A thorough discussion about possible explanations for the apparently paradoxical findings in the mouse vs the human system has recently been published (35).…”

Section: Discussionmentioning

confidence: 99%

FcγRIIB in IgG-Mediated Suppression of Antibody Responses: Different Impact In Vivo and In Vitro

Karlsson

Getahun

Heyman

2001

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…It was shown in a murine model of ITP that IVIg changes the composition of Fcc receptors on the surface of monocytes; it downregulates the phagocytic-stimulatory FccRIIIa and upregulates the inhibitory FccRIIb [5]. Alternatively, it has been suggested that anti-D may cause immunosuppression by either interacting with receptors other than FccR or stimulating the production of immunosuppressive cytokines [6]. To examine the latter possibility, we designed a prospective anti-D dose cross-over study in 7 children with chronic AITP to compare the clinical ®ndings with in vivo serum cytokine/chemokine levels.…”

Section: Introductionmentioning

confidence: 99%

Anti‐D (WinRho SD^™) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production

et al. 2002

View full text Add to dashboard Cite

Intravenous anti-D is often used in the treatment of autoimmune thrombocytopenic purpura (AITP), but little is known about its mechanisms of action. To investigate anti-D's potential in vivo mechanism(s) of action, a small group (N = 7) of children with chronic AITP was studied. The children initially received either 25 or 50 lg/kg of WinRho-SD in a four-cycle cross-over trial, and peripheral blood samples from the ®rst and third cycles were assessed for cytokine levels at pre-treatment, 3 hr, 1 day, and 8 days post-treatment. Results showed that platelet counts signi®cantly increased in all the children by day 8 post-treatment. Analysis of serum by ELISA showed that there was a signi®cant but transient rise in both pro-and anti-in¯ammatory cytokine/chemokine levels (e.g., IL1RA, IL6, GM-CSF, MCP-1a, TNF-a and MCP-1) by 3 hr post-treatment in both cycles which returned to baseline levels by 8 days post-treatment. These results suggest that anti-D administration may initially activate the RES in the form of cytokine/chemokine secretion, which is subsequently followed by an increase in platelet counts. It is possible that the induced cytokine/chemokine storm may have an effect on several physiological processes such as those mediating either adverse effects or potentially RES phagocytic activity. Am.

show abstract

“…The suppressive effect of IgG on the Ab response in the recipient has been termed Ab-mediated immune suppression (AMIS) 3 (2). The effectiveness of anti-D commonly exceeds that of the vaccine preparations, such as measles-mumpsrubella or diphtheria-tetanus toxoids-pertussis vaccines (3,4).…”

Section: Transfusion Of Igg-opsonized Foreign Red Blood Cellsmentioning

confidence: 99%

Transfusion of IgG-Opsonized Foreign Red Blood Cells Mediates Reduction of Antigen-Specific B Cell Priming in a Murine Model

Brinc

Le-Tien

Crow

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

Hemolytic disease of the fetus and newborn can be effectively prevented by administration of anti-D to the mother. The administered IgG results in the attenuation of RBC-specific Ab production, a process termed Ab-mediated immune suppression (AMIS). Because in animal models of AMIS no major effect on T cell priming occurs, we hypothesized that the effect of the IgG on the immune system under AMIS conditions may involve a deficiency in B cell priming. We therefore challenged mice with either untreated RBCs or IgG-opsonized RBCs (AMIS) and assessed B cell priming. B cells from mice transfused with untreated RBCs, but not from mice treated under AMIS conditions, were primed as assessed by their ability to function as Ag-specific APCs to appropriate T cells. To our knowledge, this is the first report demonstrating that AMIS inhibits the appearance of Ag-primed RBC-specific B cells.

show abstract

Mechanism of anti-D-mediated immune suppression – a paradox awaiting resolution?

Cited by 90 publications

References 39 publications

FcγRIIB in IgG-Mediated Suppression of Antibody Responses: Different Impact In Vivo and In Vitro

FcγRIIB in IgG-Mediated Suppression of Antibody Responses: Different Impact In Vivo and In Vitro

Anti‐D (WinRho SD^™) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production

Transfusion of IgG-Opsonized Foreign Red Blood Cells Mediates Reduction of Antigen-Specific B Cell Priming in a Murine Model

Contact Info

Product

Resources

About

Mechanism of anti-D-mediated immune suppression – a paradox awaiting resolution?

Cited by 90 publications

References 39 publications

FcγRIIB in IgG-Mediated Suppression of Antibody Responses: Different Impact In Vivo and In Vitro

FcγRIIB in IgG-Mediated Suppression of Antibody Responses: Different Impact In Vivo and In Vitro

Anti‐D (WinRho SD™) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production

Transfusion of IgG-Opsonized Foreign Red Blood Cells Mediates Reduction of Antigen-Specific B Cell Priming in a Murine Model

Contact Info

Product

Resources

About

Anti‐D (WinRho SD^™) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production