guest ::
| Home > Publications database > RNA-based full length immunoglobulin light chain sequencing reveals lambda constant domain mutations with potential implications for thermodynamic stability in light chain amyloidosis. |
| Home > Publications database > RNA-based full length immunoglobulin light chain sequencing reveals lambda constant domain mutations with potential implications for thermodynamic stability in light chain amyloidosis. |
| Journal Article | DKFZ-2026-01358 |
; ; ; ; ; ; ; ; ; ; ; ;
2026
Taylor & Francis Group
Abingdon
Abstract: Systemic light chain amyloidosis is a protein misfolding disorder characterized by deposition of clonal immunoglobulin light chains in vital organs. To date, little is known about the contribution of light chain constant domain mutations in thermodynamic stability and amyloidogenicity.In 89 patients, RNA-based full-length light chain repertoire sequencing with Oxford Nanopore was performed, in addition to Illumina sequencing and mass spectrometric detection of light chain protein in serum and amyloid deposits. Computational methods for conservation, free energy calculation and molecular dynamics simulations were applied to investigate the thermodynamic stability.Monoclonal light chain detection rate was 95.4%, and sequences showed 100% identity with Illumina in all patients. Light chain protein was specifically detectable by mass spectrometry in serum and amyloid deposits. Lambda constant domain mutations were present in 10%, while no kappa constant domain mutations were detected. Fold free energy change and molecular dynamics simulations indicate potential light chain stabilizing or destabilizing effects of detected constant domain mutations.Current findings highlight the importance of routinely implementing full-length light chain sequencing in plasma cell dyscrasias, particularly light chain amyloidosis to account for the potential impact of constant domain mutations on light chain stability and amyloidogenicity.
Keyword(s): RNA-based full-length light chain sequencing ; light chain constant domain mutations ; light chain thermodynamic stability ; long-read sequencing ; systemic light chain amyloidosis
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz
; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
|
The record appears in these collections: |
