Recently we have shown that immune-complex mediated inflammation can be blocked by recombinant dimeric FcγR-Ig molecules in a mouse Arthus reaction model. In the present study, we have investigated whether administration of FcγR-Ig would inhibit the antibody-mediated hemolytic anemia, thrombocytopenia and arthritis in a mouse model. Systemic Administration of recombinant dimeric low affinity FcγRs such as human CD32A alleles (hCD32AR-Ig and hCD32AH-Ig) did not inhibit or prevent the antibody-induced hemolytic anemia and thrombocytopenia. Interestingly, we observed that after 48 hr of administration both hCD32AR-Ig and hCD32AH-Ig were able to inhibit 27% and 42% of the arthritic inflammation respectively, whereas the combination of hCD32AR-Ig and hCD32AH-Ig was able to inhibit 52% of arthritic inflammation. The severity of arthritis as assessed by inflammation and swelling in each digit and paw was significantly reduced. A single dose of hCD32A-Ig molecules was able to reduce the severity of arthritis up to 4 days, after which the disease returned and reached the maximum severity by day 7. The relapse of arthritis might be due to other mechanisms such as complement pathways or accelerated clearance of administered FcγR-Igs in arthritis mice. In conclusion, soluble dimeric FcγR-Igs could be of potential use in treating antibody-mediated autoimmune diseases such as arthritis but not for autoimmune diseases which affect blood cells such as hemolytic anemia and thrombocytopenia
- Copyright © 2011 by The American Association of Immunologists, Inc.