PXD077140

PXD077140 is an original dataset announced via ProteomeXchange.

Title	RNA-based full length immunoglobulin light chain sequencing reveals lambda constant domain mutations with potential implications for thermodynamic stability in light chain amyloidosis
Description	Background: 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. Methods: 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. Results: 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. Conclusion: 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.
HostingRepository	PRIDE
AnnounceDate	2026-05-06
AnnouncementXML	Submission_2026-05-06_07:40:40.355.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Josefine Jakob
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	quadrupole orbitrap astral instrument

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-14 08:18:47	ID requested
⏵ 1	2026-05-06 07:40:41	announced

Dataset with its publication pending

submitter keyword: None

Björn Häupl
contact affiliation	Department of Medicine II, Hematology/Oncology, Goethe University, Frankfurt, Germany. German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
contact email	b.haeupl@dkfz-heidelberg.de
lab head
Josefine Jakob
contact affiliation	Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt, Germany Department of Medicine II, Hematology/Oncology, Goethe University, Frankfurt, Germany
contact email	j.jakob@med.uni-frankfurt.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD077140
     1. Label: PRIDE project
     2. Name: RNA-based full length immunoglobulin light chain sequencing reveals lambda constant domain mutations with potential implications for thermodynamic stability in light chain amyloidosis