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| 2. |
- Allhorn, Maria, et al.
(författare)
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The IgG specific endoglycosidase EndoS inhibits both cellular and complement mediated autoimmune hemolysis.
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 115:24, s. 5080-5088
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Tidskriftsartikel (refereegranskat)abstract
- EndoS from Streptococcus pyogenes is an immunomodulating enzyme that specifically hydrolyzes glycans from human IgG and thereby affects antibody effector functions. Autoimmune hemolytic anemia is caused by antibody mediated red blood cell (RBC) destruction and often resists treatment with corticosteroids that also cause frequent adverse effects. We show here that anti-RhD (anti-D) and rabbit anti-human-RBC antibodies (anti-RBC) mediated destruction of RBC, i.e. phagocytosis, complement activation and hemolysis in vitro and in vivo was inhibited by EndoS. Phagocytosis by monocytes in vitro was inhibited by pre-treatment of anti-D with EndoS before sensitization of RBC, and abrogated by direct addition of EndoS to blood containing sensitized RBC. The toxic effects of monocytes stimulated with anti-D-sensitized RBC, as measured by interleukin-8 secretion and oxygen metabolite production, was restrained by EndoS. Agglutination of RBC and complement mediated hemolysis in vitro in whole human blood caused by rabbit anti-RBC was inhibited by EndoS. Development of anemia in mice caused by a murine anti-RBC IgG2a monoclonal autoantibody, and complement activation and erythrophagocytosis by Kupffer cells in the liver, were reduced by EndoS. Our data indicate that EndoS is a potential therapeutic agent that might be evaluated as an alternative to current treatment regimens against antibody mediated destruction of RBC.
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| 3. |
- Fossati-Jimack, Liliane, et al.
(författare)
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Selective increase of autoimmune epitope expression on aged erythrocytes in mice : implications in anti-erythrocyte autoimmune responses
- 2002
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Ingår i: Journal of Autoimmunity. - : Academic Press. - 0896-8411 .- 1095-9157. ; 18:1, s. 17-25
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the impact of changes occurring during red blood cell (RBC) ageing on the RBC-binding activity of pathogenic anti-erythrocyte monoclonal antibodies derived from autoimmune-prone New Zealand black (NZB) mice. As assessed by flow cytometric analysis on in vivo biotinylated RBCs, all five NZB-derived anti-RBC mAb exhibited more efficient binding to aged RBCs than to young RBCs, and resulted in a selective elimination of more aged RBCs from the circulating blood. In addition, treatment of RBCs with proteases markedly enhanced the binding of all five anti-RBC mAb, raising the possibility that increased exposure of autoimmune epitopes on aged RBCs may be in part, a result of contacts with proteolytic enzymes during the lifetime of circulating RBCs. In marked contrast, the binding activity of mAb raised in non-autoimmune animals against antigens expressed on RBCs, such as CD44, CD47, CD147 and TER-119, was either decreased or unchanged with RBC ageing, and these epitopes, except for that recognized by anti-CD47 mAb, were highly sensitive to mild treatment with proteases. Our data unravel the unique molecular feature of RBC epitopes involved in autoimmune haemolytic anaemia, suggesting that membrane alterations in aged RBCs might play a significant role in the development of the autoantibody response to RBCs.
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| 4. |
- Oldenborg, Per-Arne, et al.
(författare)
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Lethal autoimmune hemolytic anemia in CD47-deficient nonobese diabetic (NOD) mice.
- 2002
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Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 99:10, s. 3500-4
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Tidskriftsartikel (refereegranskat)abstract
- The glycoprotein CD47 (integrin-associated protein, IAP) is present on the surface of virtually all cells, including red blood cells (RBCs). CD47 acts like a marker of self by ligating the macrophage inhibitory receptor signal regulatory protein alpha (SIRPalpha). In this manner mild reactivity of wild-type RBCs with macrophage phagocytic receptors is tolerated, whereas otherwise identical CD47-deficient RBCs are rapidly eliminated. We show here that virtually all CD47-deficient nonobese diabetic (NOD) mice spontaneously develop severe lethal autoimmune hemolytic anemia (AIHA) at 180 to 280 days of age, whereas none of the control CD47(+) NOD mice develop lethal AIHA at least during the first year of life. This phenotype is at least partially due to a markedly increased rate of elimination of opsonized CD47(-/-) compared to CD47(+) RBCs. Similarly, CD47(-/-)C57BL/6 mice were much more sensitive than their wild-type counterparts to experimental passive AIHA induced by anti-RBC monoclonal antibodies. Thus, CD47-SIRPalpha signaling can have a profound influence on the severity of AIHA, making manipulation of this signaling pathway a theoretically appealing avenue in the treatment of the disease.
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| 6. |
- Wermeling, Fredrik, et al.
(författare)
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Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus
- 2007
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 204:10, s. 2259-2265
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Tidskriftsartikel (refereegranskat)abstract
- Apoptotic cells are considered to be a major source for autoantigens in autoimmune diseases such as systemic lupus erythematosus (SLE). In agreement with this, defective clearance of apoptotic cells has been shown to increase disease susceptibility. Still, little is known about how apoptotic cell-derived self-antigens activate autoreactive B cells and where this takes place. In this study, we find that apoptotic cells are taken up by specific scavenger receptors expressed on macrophages in the splenic marginal zone and that mice deficient in these receptors have a lower threshold for autoantibody responses. Furthermore, antibodies against scavenger receptors are found before the onset of clinical symptoms in SLE-prone mice, and they are also found in diagnosed SLE patients. Our findings describe a novel mechanism where autoantibodies toward scavenger receptors can alter the response to apoptotic cells, affect tolerance, and thus promote disease progression. Because the autoantibodies can be detected before onset of disease in mice, they could have predictive value as early indicators of SLE.
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