Diverse patterns of antibody variable gene repertoire disruption in patients with amyloid light chain (AL) amyloidosis.
Immunoglobulin light chain amyloidosis is the most common form of systemic amyloidosis. AL amyloidosis is caused by a misfolded light chain produced by a clonal population of plasma cells. Disease status currently is defined by measuring the absolute quantity of serum free light chain protein, but t...
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doaj-1e0d12326e3f4900985b6fa03650e87a2021-03-26T05:30:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01157e023571310.1371/journal.pone.0235713Diverse patterns of antibody variable gene repertoire disruption in patients with amyloid light chain (AL) amyloidosis.Elaine C ChenSamuel RubinsteinCinque SotoRobin G BombardiSamuel B DayLuke MyersAlexey ZaytsevMahsa MajediR Frank CornellJames E CroweImmunoglobulin light chain amyloidosis is the most common form of systemic amyloidosis. AL amyloidosis is caused by a misfolded light chain produced by a clonal population of plasma cells. Disease status currently is defined by measuring the absolute quantity of serum free light chain protein, but this measurement often fails to identify the subclinical presence of clonal cells that may merit additional therapy. Next generation sequencing has the sensitivity to measure the relative amount of dominating light chains within the repertoire of a patient, and this technique is in clinical use to identify clonal populations of plasma cells for multiple myeloma, a related disorder. In this proof-of-concept study, we used bone marrow aspirates of AL amyloidosis positive patients and used reverse transcription of the antibody transcriptome followed by next generation sequencing to identify antibody variable-diversity-joining gene sequences for patients with immunoglobulin light chain amyloidosis, and demonstrate that this technology can be used to identify the dominant clone. The data also reveal differing patterns of overall antibody repertoire disruption in different patients. This method merits further study in larger prospective studies to establish its utility in detecting residual disease for patients with immunoglobulin light chain amyloidosis.https://doi.org/10.1371/journal.pone.0235713 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elaine C Chen Samuel Rubinstein Cinque Soto Robin G Bombardi Samuel B Day Luke Myers Alexey Zaytsev Mahsa Majedi R Frank Cornell James E Crowe |
spellingShingle |
Elaine C Chen Samuel Rubinstein Cinque Soto Robin G Bombardi Samuel B Day Luke Myers Alexey Zaytsev Mahsa Majedi R Frank Cornell James E Crowe Diverse patterns of antibody variable gene repertoire disruption in patients with amyloid light chain (AL) amyloidosis. PLoS ONE |
author_facet |
Elaine C Chen Samuel Rubinstein Cinque Soto Robin G Bombardi Samuel B Day Luke Myers Alexey Zaytsev Mahsa Majedi R Frank Cornell James E Crowe |
author_sort |
Elaine C Chen |
title |
Diverse patterns of antibody variable gene repertoire disruption in patients with amyloid light chain (AL) amyloidosis. |
title_short |
Diverse patterns of antibody variable gene repertoire disruption in patients with amyloid light chain (AL) amyloidosis. |
title_full |
Diverse patterns of antibody variable gene repertoire disruption in patients with amyloid light chain (AL) amyloidosis. |
title_fullStr |
Diverse patterns of antibody variable gene repertoire disruption in patients with amyloid light chain (AL) amyloidosis. |
title_full_unstemmed |
Diverse patterns of antibody variable gene repertoire disruption in patients with amyloid light chain (AL) amyloidosis. |
title_sort |
diverse patterns of antibody variable gene repertoire disruption in patients with amyloid light chain (al) amyloidosis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2020-01-01 |
description |
Immunoglobulin light chain amyloidosis is the most common form of systemic amyloidosis. AL amyloidosis is caused by a misfolded light chain produced by a clonal population of plasma cells. Disease status currently is defined by measuring the absolute quantity of serum free light chain protein, but this measurement often fails to identify the subclinical presence of clonal cells that may merit additional therapy. Next generation sequencing has the sensitivity to measure the relative amount of dominating light chains within the repertoire of a patient, and this technique is in clinical use to identify clonal populations of plasma cells for multiple myeloma, a related disorder. In this proof-of-concept study, we used bone marrow aspirates of AL amyloidosis positive patients and used reverse transcription of the antibody transcriptome followed by next generation sequencing to identify antibody variable-diversity-joining gene sequences for patients with immunoglobulin light chain amyloidosis, and demonstrate that this technology can be used to identify the dominant clone. The data also reveal differing patterns of overall antibody repertoire disruption in different patients. This method merits further study in larger prospective studies to establish its utility in detecting residual disease for patients with immunoglobulin light chain amyloidosis. |
url |
https://doi.org/10.1371/journal.pone.0235713 |
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