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Measuring the Impact of Targeting FcRn-Mediated IgG Recycling on Donor-Specific Alloantibodies in a Sensitized NHP Model
- Source :
- Frontiers in Immunology, Vol 12 (2021), Frontiers in Immunology
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- BackgroundIn transplantation, plasmapheresis and IVIg provide the mainstay of treatment directed at reducing or removing circulating donor-specific antibody (DSA), yet both have limitations. We sought to test the efficacy of targeting the IgG recycling mechanism of the neonatal Fc receptor (FcRn) using anti-FcRn mAb therapy in a sensitized non-human primate (NHP) model, as a pharmacological means of lowering DSA.MethodsSix (6) rhesus macaque monkeys, previously sensitized by skin transplantation, received a single dose of 30mg/kg anti-RhFcRn IV, and effects on total IgG, as well as DSA IgG, were measured, in addition to IgM and protective immunity. Subsequently, 60mg/kg IV was given in the setting of kidney transplantation from skin graft donors. Kidney transplant recipients received RhATG, and tacrolimus, MMF, and steroid for maintenance immunosuppression.ResultsCirculating total IgG was reduced from a baseline 100% on D0 to 32.0% (mean, SD ± 10.6) on d4 post infusion (pConclusionTargeting the FcRn-mediated recycling of IgG is an effective means of lowering circulating donor-specific IgG in the sensitized recipient, although in the setting of organ transplantation mechanisms of rapid antibody rise post-transplant remains unaffected.
- Subjects :
- Graft Rejection
Male
0301 basic medicine
medicine.medical_treatment
Receptors, Fc
030230 surgery
sensitization
Organ transplantation
0302 clinical medicine
Isoantibodies
Immunology and Allergy
Medicine
Kidney transplantation
Original Research
biology
Histocompatibility Testing
Graft Survival
Antibodies, Monoclonal
Immunoglobulins, Intravenous
Immunosuppression
Tissue Donors
non-human primate (NHP)
Models, Animal
Antibody
Immunosuppressive Agents
medicine.medical_specialty
IgG
medicine.drug_class
Immunology
Monoclonal antibody
03 medical and health sciences
Neonatal Fc receptor
alloantibody
Animals
Immunosuppression Therapy
business.industry
Histocompatibility Antigens Class I
RC581-607
medicine.disease
Kidney Transplantation
Macaca mulatta
Transplantation
FcRn
030104 developmental biology
Immunoglobulin G
biology.protein
Plasmapheresis
Immunologic diseases. Allergy
business
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....4c6f2e52a006e7b011d704e9c221784f