Schaefer, Nicole and Grosche, Antje and Reinders, Joerg and Hauck, Stefanie M. and Pouw, Richard B. and Kuijpers, Taco W. and Wouters, Diana and Ehrenstein, Boris and Enzmann, Volker and Zipfel, Peter F. and Skerka, Christine and Pauly, Diana (2016) Complement Regular FHR-3 Is Elevated either Locally or Systemically in a Selection of Autoimmune Diseases. FRONTIERS IN IMMUNOLOGY, 7: 542. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
The human complement factor H-related protein-3 (FHR-3) is a soluble regulator of the complement system. Homozygous cfhr3/1 deletion is a genetic risk factor for the autoimmune form of atypical hemolytic-uremic syndrome (aHUS), while also found to be protective in age-related macular degeneration (AMD). The precise function of FHR-3 remains to be fully characterized. We generated four mouse monoclonal antibodies (mAbs) for FHR-3 (RETC) without cross-reactivity to the complement factor H (FH)-family. These antibodies detected FHR-3 from human serum with a mean concentration of 1 mu g/mL. FHR-3 levels in patients were significantly increased in sera from systemic lupus erythematosus, rheumatoid arthritis, and polymyalgia rheumatica but remained almost unchanged in samples from AMD or aHUS patients. Moreover, by immunostaining of an aged human donor retina, we discovered a local FHR-3 production by microglia/macrophages. The mAb RETC-2 modulated FHR-3 binding to C3b but not the binding of FHR-3 to heparin. Interestingly, FHR-3 competed with FH for binding C3b and the mAb RETC-2 reduced the interaction of FHR-3 and C3b, resulting in increased FH binding. Our results unveil a previously unknown systemic involvement of FHR-3 in rheumatoid diseases and a putative local role of FHR-3 mediated by microglia/macrophages in the damaged retina. We conclude that the local FHR-3/FH equilibrium in AMD is a potential therapeutic target, which can be modulated by our specific mAb RETC-2.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | H-RELATED PROTEINS; HEMOLYTIC-UREMIC SYNDROME; GIANT-CELL ARTERITIS; MACULAR DEGENERATION; POLYMYALGIA-RHEUMATICA; MONOCLONAL-ANTIBODIES; IMMUNE-COMPLEXES; BINDING; CFH; ACTIVATION; FHR-3/CFHR3; specific antibody; rheumatic disease; microglia/macrophage; FH competition; immune therapy; retinal degeneration |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Apr 2019 10:02 |
| Last Modified: | 12 Apr 2019 10:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3932 |
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