**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Joseph Jackson, University of Tennessee Graduate School of Medicine, Knoxville, TN, USA.

**Main Body of the Abstract**
Background: Systemic amyloid deposits are characteristically acellular with no surrounding inflammatory reaction. We initially speculated that the lack of immune infiltrate into amyloid deposits results from immunologic indifference towards amyloid. However, recent studies have revealed that a subset of AL patient derived amyloid material is readily recognized and engulfed by macrophages (PMID:36541892). Even so, tissue sections from these patients indicated that amyloid deposits are immunologically acellular in areas of heavy amyloid deposition. We hypothesized that amyloid toxicity could induce an immunologic acellular environment in vivo. In vitro  studies have indicated that purified amyloidogenic light chains induce cardiomyocyte toxicity, but analysis of human amyloid extract material, has not been similarly evaluated.
Methods: Using human-derived amyloid extract from AL patients, we assayed amyloid uptake and the correlation between uptake and cell death by flow cytometry using human macrophage, hepatocyte, and cardiomyocyte cell lines.
Results: Cell death, of all cells analyzed, coincided with amyloid uptake and this relationship had a positive correlation. Additional studies in macrophages analyzing amyloid binding versus amyloid uptake indicated that amyloid binding to macrophages does not induce cell death, rather toxicity is induced upon engulfment of amyloid material. We next sought to opsonize amyloid material to assess the impact of FcR mediated phagocytosis on toxicity. Amyloid opsonization protected macrophages from amyloid-induced death in a dose dependent manner.
Conclusion: These results indicate that uptake of amyloid through non-FcR mediated phagocytosis by macrophages induces cellular toxicity, but opsonization can circumvent amyloid induced toxicity, underscoring the importance of opsonic amyloid-reactive therapeutics.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Joseph Jackson, University of Tennessee Graduate School of Medicine, Knoxville, TN, USA.

**Main Body of the Abstract**
**Background:** Systemic amyloid deposits are characteristically acellular with no surrounding inflammatory reaction. We initially speculated that the lack of immune infiltrate into amyloid deposits results from immunologic indifference towards amyloid. However, recent studies have revealed that a subset of AL patient derived amyloid material is readily recognized and engulfed by macrophages (PMID:36541892). Even so, tissue sections from these patients indicated that amyloid deposits are immunologically acellular in areas of heavy amyloid deposition. We hypothesized that amyloid toxicity could induce an immunologic acellular environment _in vivo. In vitro_  studies have indicated that purified amyloidogenic light chains induce cardiomyocyte toxicity, but analysis of human amyloid extract material, has not been similarly evaluated.
**Methods:** Using human-derived amyloid extract from AL patients, we assayed amyloid uptake and the correlation between uptake and cell death by flow cytometry using human macrophage, hepatocyte, and cardiomyocyte cell lines.
**Results:** Cell death, of all cells analyzed, coincided with amyloid uptake and this relationship had a positive correlation. Additional studies in macrophages analyzing amyloid binding versus amyloid uptake indicated that amyloid binding to macrophages does not induce cell death, rather toxicity is induced upon engulfment of amyloid material. We next sought to opsonize amyloid material to assess the impact of FcR mediated phagocytosis on toxicity. Amyloid opsonization protected macrophages from amyloid-induced death in a dose dependent manner.
**Conclusion:** These results indicate that uptake of amyloid through non-FcR mediated phagocytosis by macrophages induces cellular toxicity, but opsonization can circumvent amyloid induced toxicity, underscoring the importance of opsonic amyloid-reactive therapeutics.



Patient derived AL amyloid induces cellular toxicity in macrophages, hepatocytes, and cardiomyocytes upon cellular engulfment of amyloid material OA8 (#181)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.