**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.**
Murielle ROUSSEL, CRIBL unit, UMR CNRS 7276, INSERM 1262, University of Limoges and French National Reference Centre for AL Amyloidosis and Other Monoclonal Ig Deposition Diseases, University Hospital of Limoges and Poitiers, France

**Main Body of the Abstract**
Since 2020, we analyzed mRNA encoding immunoglobulins by high-throughput sequencing assay (RACE-RepSeq) in 427 bone marrow samples from patients with suspected gammopathies-related diseases, mainly including AL amyloidosis (n=214), and POEMS syndrome (n=62). This technique provides full-length V(D)J region of the dominant immunoglobulin repertoire, allowing analysis of mutational patterns, immunoglobulin variable gene frequencies and diversity due to somatic hypermutation. We were able to review clinical, histological and FLC data in 91% of patients resulting in a complete and accurate database of AL (n=199), POEMS (n=73) and other monoclonal gammopathies of clinical significance (n=144). 
In AL amyloidosis, 41 patients did not meet proper diagnosis criteria and the involved clone was found in 99.4%. In lambda patients (n=119), we confirmed the predominance of IGLV2-14 (n=31), IGLV6-57 (n=21), IGLV1-44 (n=14,) and IGLV3-1 (n=14). In kappa patients (n=38), IGKV gene frequencies were as followed: IGKV1-33 n=12, IGKV1-16 n=6, IGKV1-39 n=4, and IgKV3-15 n=4.
Median levels of iFLC were lower in lambda vs kappa patients (168 vs 256.5 mg/l) and different according to the 5 dominant “amyloidogenic” IGV: 87,8 in IGLV6-57, 156,5 in IGLV1-44, 226 in IGLV2-14, 349 in IGLV3-1 to 652 in IGKV1-33.
The majority of patients had kidney (66%) and cardiac involvement (61.5%) followed by nerve (36.5%), liver (29.5%) and GI tract (23.5%). Respective IGV restrictions are summarized in table 1.
This unique database allowed us to establish predictive scores for amyloidogenicity and/or toxicity according to light chain physicochemical caracteristics and to compare them to the current available tools (LICTOR and VLamyPred) (up-coming data).



**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.**
Murielle ROUSSEL, _CRIBL unit, UMR CNRS 7276, INSERM 1262, University of Limoges and French National Reference Centre for AL Amyloidosis and Other Monoclonal Ig Deposition Diseases, University Hospital of Limoges and Poitiers, France_

**Main Body of the Abstract**
Since 2020, we analyzed mRNA encoding immunoglobulins by high-throughput sequencing assay (RACE-RepSeq) in 427 bone marrow samples from patients with suspected gammopathies-related diseases, mainly including AL amyloidosis (n=214), and POEMS syndrome (n=62). This technique provides full-length V(D)J region of the dominant immunoglobulin repertoire, allowing analysis of mutational patterns, immunoglobulin variable gene frequencies and diversity due to somatic hypermutation. We were able to review clinical, histological and FLC data in 91% of patients resulting in a complete and accurate database of AL (n=199), POEMS (n=73) and other monoclonal gammopathies of clinical significance (n=144). 
In AL amyloidosis, 41 patients did not meet proper diagnosis criteria and the involved clone was found in 99.4%. In lambda patients (n=119), we confirmed the predominance of IGLV2-14 (n=31), IGLV6-57 (n=21), IGLV1-44 (n=14,) and IGLV3-1 (n=14). In kappa patients (n=38), IGKV gene frequencies were as followed: IGKV1-33 n=12, IGKV1-16 n=6, IGKV1-39 n=4, and IgKV3-15 n=4.
Median levels of iFLC were lower in lambda vs kappa patients (168 vs 256.5 mg/l) and different according to the 5 dominant “amyloidogenic” IGV: 87,8 in IGLV6-57, 156,5 in IGLV1-44, 226 in IGLV2-14, 349 in IGLV3-1 to 652 in IGKV1-33.
The majority of patients had kidney (66%) and cardiac involvement (61.5%) followed by nerve (36.5%), liver (29.5%) and GI tract (23.5%). Respective IGV restrictions are summarized in table 1.
This unique database allowed us to establish predictive scores for amyloidogenicity and/or toxicity according to light chain physicochemical caracteristics and to compare them to the current available tools (LICTOR and VLamyPred) (up-coming data).



RNA-based Immunoglobulin repertoire sequencing is a useful tool for prediction and management of AL amyloidosis along with monoclonal gammopathies of clinical significance PA46 (#517)

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.