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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Unlike C3 and factor B (FB), which are primarily synthesized in the liver, factor D (FD) — a serine protease of complement alternative pathway (AP) — is synthesized in fat tissue. Recent studies have revealed that FD is secreted as pro-FD with minimal activity, which is then converted into mature FD by MBL-associated serine protease-3 (MASP-3) upon activation.
It has also been reported that in mice and humans deficient in MASP-3, FD exists as pro-FD with low activity, resulting in a significant reduction in the activity of the AP.
Initially, we attempted to restore AP activity in FD knockout (FDKO) mice using an adeno-associated virus (AAV) vector. Contrary to expectation, however, we observed a loss of AP activity. Consequently, we conducted this study to elucidate the underlying mechanism of this phenomenon and explore its potential therapeutic applications.
We expressed mature or pro-FD in the liver or bone marrow/blood cells of mice using AAV8 and retrovirus-mediated gene transduction, respectively, and evaluated FD and AP complement activity in the treated mice.
Hepa1-6 cells were used for transfection experiments with C3, FB, and FD genes.
For therapeutic application experiments, the FHR/R(atypical hemolytic uremic syndrome) and FHm/mP-/- (C3 glomerulopathy) mouse models, which we had previously reported, were adopted as complement-mediated disease models.
In an initial experiment, we attempted to restore plasma FD and AP complement activity in FD KO mice by AAV8/mature FD gene transduction which primarily targets liver cells. Unexpectedly, despite successful restoration of plasma FD, AP complement activity was not recovered in the treated mice. Further investigation showed that plasma FB was mostly missing in the AAV8/mature FD-treated FD KO mice. Similar FB depletion also occurred in wild-type but not C3 KO mice after AAV8/mature FD treatment.
Conversely, depletion of FB was not observed in mice treated with AAV8/pro-FD gene transduction or in mice with ectopic expression of mature FD in bone marrow/blood cells via retrovirus-mediated gene transduction.
When Hepa1-6 cells were induced to express C3, FB and mature FD, intact FB was lost from the culture supernatant. Vemircopan was able to prevent FB depletion, unlike FD monoclonal antibody.
Finally, the depletion of FB by AAV8/mature FD effectively prevented the development of disease in murine models of atypical hemolytic uremic syndrome and C3 glomerulopathy.
Our data suggest that the regulation of FD by MASP3 and the segregated biosynthesis of FD, FB and C3 have physiological significance. The ectopic expression of mature FD in the liver causes C3-dependent FB depletion, a phenomenon that could be exploited for the treatment of complement-mediated AP diseases.
