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Antigen modulation as a potential mechanism of anti-KEL immunoprophylaxis in mice
- Source :
- Blood. 128:3159-3168
- Publication Year :
- 2016
- Publisher :
- American Society of Hematology, 2016.
-
Abstract
- Red blood cell (RBC) alloimmunization is a serious complication of transfusion or pregnancy. Despite the widespread use of Rh immune globulin to prevent pregnancy associated anti-D alloimmunization, its mechanism of action remains elusive. We have previously described a murine model in which immunoprophylaxis with polyclonal anti-KEL sera prevents alloimmunization in wild-type recipients transfused with transgenic murine RBCs expressing the human KEL glycoprotein. To investigate the mechanism of action, we have now evaluated the outcome of immunoprophylaxis treatment in mice lacking Fcγ receptors (FcγRs), complement (C3), both, or none. Whereas polyclonal anti-KEL sera completely prevented alloimmunization in wild-type and single-knockout (KO) mice lacking FcγRs or C3, double-KO mice lacking both FcγRs and C3 became alloimmunized despite immunoprophylaxis. Rapid clearance of essentially all transfused RBCs with detectable KEL glycoprotein antigen occurred within 24 hours in wild-type and single-KO recipients treated with immunoprophylaxis, with the transfused RBCs remaining in circulation having minimal KEL glycoprotein antigen detectable by flow cytometry or western blot. In contrast, transfused RBCs with the KEL glycoprotein antigen fully intact continued to circulate for days in double-KO mice despite treatment with immunoprophylaxis. Further, in vitro phagocytosis assays showed no consumption of opsonized murine RBCs by double-KO splenocytes. Taken in combination, our data suggest that modulation of the KEL antigen (and potentially RBC clearance) by redundant recipient pathways involving both FcγRs and C3 may be critical to the mechanism of action of polyclonal anti-KEL immunoprophylaxis. These findings could have implications for the development of immunoprophylaxis programs in humans.
- Subjects :
- Male
Erythrocytes
Phagocytosis
Blotting, Western
Immunology
030204 cardiovascular system & hematology
Biochemistry
Flow cytometry
Mice
03 medical and health sciences
Antigenic Modulation
0302 clinical medicine
Antigen
medicine
Splenocyte
Animals
Humans
Blood Transfusion
Antigens
Receptors, Immunologic
Opsonin
Crosses, Genetic
Mice, Knockout
chemistry.chemical_classification
Membrane Glycoproteins
medicine.diagnostic_test
biology
Transfusion Medicine
business.industry
Metalloendopeptidases
Complement C3
Cell Biology
Hematology
Opsonin Proteins
Virology
Antibodies, Anti-Idiotypic
Mice, Inbred C57BL
Red blood cell
medicine.anatomical_structure
chemistry
Polyclonal antibodies
biology.protein
Immunization
Glycoprotein
business
Spleen
030215 immunology
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 128
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....e78c92f0ee92fef349106a17bb8437b8
- Full Text :
- https://doi.org/10.1182/blood-2016-06-724732