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Updated: Jun 6, 2026
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
RNA-based full length immunoglobulin light chain sequencing reveals lambda constant domain mutations with potential
Eyad Naser1, Sara Oubari2,3, Josefine Jakob4,5
1Institute of Molecular Biology, University Duisburg-Essen, Essen, Germany.
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.
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