**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.**
Charalampos Charalampous, Mayo Clinic, Rochester, Minnesota

**Main Body of the Abstract**
The mechanisms behind kidney damage in AL remain unclear, and unraveling those could lead to novel therapies.
Our prior work has demonstrated increased T cell subsets in the bone marrow of AL patients compared to other dysproteinemias.
We sought to characterize the immunome of renal AL and its correlation with clinical outcomes.
Using imaging mass cytometry, we explored the single-cell, spatial immune landscape of 45 renal AL biopsies. We included 17 control cases (10 nephrotic syndromes, 7 normal).
A total of 25630 CD45+ cells were analyzed. B cells were lower in amyloid cases than controls (p<0.001), which is likely secondary to systemic immunoparesis in AL. T-cells were increased in AL compared to disease/normal controls (16% vs. 2.3% vs. 1.9%, p<0.001) and in AL renal stage 2/3 vs. 1 (18% vs 3.5%, p=0.002). This was true for several cytotoxic T cell subsets, including HLA-DR+ T cells, a highly activated subset (p=0.003). Principal component (PC) analyses based on immune composition, identified two groups of patients (PC1 high and low). PC1-high patients had lower renal survival, an overrepresentation of several T cell subsets, antigen-presenting cells, and CD11c+ positive B cells, a subset associated with autoimmune disease. Interestingly, T-cells and CD11c+ B cells were spatially closer to glomeruli (p<0.01 and <0.001, respectively) and further away from vessels than controls (p<0.001 for both), which suggests active extravasation/chemotaxis towards glomeruli.
This work, along with other work presented in this meeting, supports the novel hypothesis of an immune-mediated tissue damage mechanism in AL.



Single-cell, spatial analysis of the renal AL immunome supports a T-cell mediated tissue toxicity mechanism OA9 (#333)

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.