**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.**
Shuang Wang, Laboratory of Electron Microscopy, Pathological Center, Peking University First Hospital, Beijing, China.

**Main Body of the Abstract**
Introduction: Amyloid light chain (AL) amyloidosis is a protein conformational disease derived from the misfolded immunoglobulin light chain (LC). The great diversity of the LCs repertoire makes it difficult to identify the pathogenic LCs definitely. In this study, we identify the complete sequence of pathogenic LCs by combing RNA-based sequencing and mass spectrometry (MS).
Methods: 12 patients with biopsy-proven AL amyloidosis were included. Total RNA was extracted from bone marrow and for RNA-based sequencing. The pathogenic LCs were extracted from urine of the same patient by affinity chromatography, MS was applied to identify the repertoire and sequences of LCs, full length sequences of LCs were determined by combing RNA-based sequencing and MS analysis. 
Results: Among these 12 patients with AL amyloidosis, serum or urine immunofixation electrophoresis (IFE) detected clonal immunoglobulin in 10 patients, bone marrow flow cytometry detected abnormal plasma cell clone in 9 of 11 patients. By RNA-based sequencing, an IGVL dominant clonotype was identified in 11 patients, ranging from 20.4% to 94.7%. By MS analysis, VL dominant clonotype was determined in 7 patients, CL dominant clonotype was identified in all patients. The sequence coverage of VL and CL dominant clonotype detected by MS ranged from 12% to 47%, 91% to 100%, respectively. When combing RNA-based sequencing and MS analysis, the complete LCs dominant clonotype, along with the full-length sequences were determined in all patients.
Conclusion: RNA-based sequencing, combined with MS analysis can provide the full-length sequences and determined the pathogenic clonotype of LCs in AL patients.



**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.**
Shuang Wang, Laboratory of Electron Microscopy, Pathological Center, Peking University First Hospital, Beijing, China.

**Main Body of the Abstract**
**Introduction:** Amyloid light chain (AL) amyloidosis is a protein conformational disease derived from the misfolded immunoglobulin light chain (LC). The great diversity of the LCs repertoire makes it difficult to identify the pathogenic LCs definitely. In this study, we identify the complete sequence of pathogenic LCs by combing RNA-based sequencing and mass spectrometry (MS).
**Methods:** 12 patients with biopsy-proven AL amyloidosis were included. Total RNA was extracted from bone marrow and for RNA-based sequencing. The pathogenic LCs were extracted from urine of the same patient by affinity chromatography, MS was applied to identify the repertoire and sequences of LCs, full length sequences of LCs were determined by combing RNA-based sequencing and MS analysis. 
**Results:** Among these 12 patients with AL amyloidosis, serum or urine immunofixation electrophoresis (IFE) detected clonal immunoglobulin in 10 patients, bone marrow flow cytometry detected abnormal plasma cell clone in 9 of 11 patients. By RNA-based sequencing, an IGVL dominant clonotype was identified in 11 patients, ranging from 20.4% to 94.7%. By MS analysis, VL dominant clonotype was determined in 7 patients, CL dominant clonotype was identified in all patients. The sequence coverage of VL and CL dominant clonotype detected by MS ranged from 12% to 47%, 91% to 100%, respectively. When combing RNA-based sequencing and MS analysis, the complete LCs dominant clonotype, along with the full-length sequences were determined in all patients.
**Conclusion:** RNA-based sequencing, combined with MS analysis can provide the full-length sequences and determined the pathogenic clonotype of LCs in AL patients.



Sequencing of amyloidogenic monoclonal immunoglobulin light chain repertoires from AL patients by combing RNA-based assay and mass spectrometry PA37 (#259)

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.