PMID- 19570063 OWN - NLM STAT- MEDLINE DCOM- 20100108 LR - 20121115 IS - 1423-0410 (Electronic) IS - 0042-9007 (Linking) VI - 97 IP - 4 DP - 2009 Nov TI - A pair of naturally occurring antibodies may dampen complement-dependent phagocytosis of red cells with a positive antiglobulin test in healthy blood donors. PG - 338-47 LID - 10.1111/j.1423-0410.2009.001214.x [doi] AB - BACKGROUND AND OBJECTIVE: It is known that red blood cells (RBC) from healthy blood donors with a positive direct antiglobulin test (DAT) for IgG continue to circulate despite carrying elevated numbers of IgG molecules. To unravel the properties of these RBC-bound IgG, we studied them not only on whole RBC populations, but also on density-fractionated RBCs. MATERIALS AND METHODS: The properties of acid-eluted RBC-bound IgG and plasma IgG were studied by ELISA for binding to RBC proteins and opsonins, and by blotting. In vitro phagocytosis was studied on density-separated RBCs. RESULTS: IgG-DAT-positive blood donors carried most IgG molecules on dense RBCs and had more RBCs of high density than DAT-negative controls. Their densest RBCs were older than the oldest RBCs of DAT-negative controls, based on the band 4.1a/b ratio. In vitro phagocytosis of senescent RBCs from IgG-DAT-positive donors was 1.5 to 2 fold higher than that of senescent control cells, but the same or less in the presence of physiological IgG concentrations, implying that RBC-bound IgGs impaired complement-dependent uptake. The IgG molecules on these DAT-positive RBCs comprised anti-band 3 naturally occurring antibodies (NAbs) and were two- to fivefold enriched in anti-C3 and framework-specific anti-idiotypic NAbs as compared to controls. Correspondingly, anti-C3 and framework-specific anti-idiotypic NAbs were proportionally elevated in the plasma of two-thirds of DAT+ donors. CONCLUSIONS: Extra-binding of anti-C3 together with anti-idiotypic NAbs to senescent RBC-associated C3 fragments may suppress complement-dependent RBC phagocytosis and may prolong the in vivo life span of RBCs. FAU - Alaia, V AU - Alaia V AD - Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland. FAU - Frey, B M AU - Frey BM FAU - Siderow, A AU - Siderow A FAU - Stammler, P AU - Stammler P FAU - Kradolfer, M AU - Kradolfer M FAU - Lutz, H U AU - Lutz HU LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090630 PL - England TA - Vox Sang JT - Vox sanguinis JID - 0413606 RN - 0 (Antibodies, Anti-Idiotypic) RN - 0 (Complement C3) RN - 0 (Immunoglobulin G) SB - IM MH - Antibodies, Anti-Idiotypic/*immunology MH - *Blood Donors MH - Complement C3/*immunology MH - *Coombs Test MH - Erythrocytes/*immunology MH - Humans MH - Immunoglobulin G/*immunology MH - Phagocytosis/*immunology EDAT- 2009/07/03 09:00 MHDA- 2010/01/09 06:00 CRDT- 2009/07/03 09:00 PHST- 2009/07/03 09:00 [entrez] PHST- 2009/07/03 09:00 [pubmed] PHST- 2010/01/09 06:00 [medline] AID - VOX1214 [pii] AID - 10.1111/j.1423-0410.2009.001214.x [doi] PST - ppublish SO - Vox Sang. 2009 Nov;97(4):338-47. doi: 10.1111/j.1423-0410.2009.001214.x. Epub 2009 Jun 30.