| Title: |
RNA-based immunoglobulin repertoire sequencing is a new tool for the management of monoclonal gammopathy of renal (kidney) significance |
| Authors: |
Javaugue, Vincent; Pascal, Virginie; Bender, Sébastien; Nasraddine, Sarah; Dargelos, Mathilde; Alizadeh, Mehdi; Saintamand, Alexis; Filloux, Matthieu; Derouault, Paco; Bouyer, Sabrina; Desport, Estelle; Jaccard, Arnaud; Bridoux, Frank; Cogné, Michel; Sirac, Christophe |
| Contributors: |
Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST); Université de Limoges (UNILIM)-Université de Limoges (UNILIM); Centre hospitalier universitaire de Poitiers = Poitiers University Hospital (CHU de Poitiers La Milétrie ); CHU Limoges; Etablissement français du sang Rennes (EFS Bretagne); Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC); Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique); This work was supported by grants from AREN Poitou-Charentes, Comitéd’Orientation de la Recherche en Cancérologie (CORC), Limousin committees of Liguenationale contre le cancer, Agence régionale de la santé, Institut Universitaire de France,“Association Française contre l’Amylose” and “Fondation Française pour la Recherche contrele Myélome et les Gammapathies” The authors acknowledge A. Rinsant and A. Lehericy fortheir technical assistance and E. Guerin of the sequencing technical plateform of CHU Limoges |
| Source: |
ISSN: 0085-2538. |
| Publisher Information: |
HAL CCSD; Nature Publishing Group |
| Publication Year: |
2022 |
| Collection: |
Université de Rennes 1: Publications scientifiques (HAL) |
| Subject Terms: |
AL-amyloidosis; Ig; monoclonal gammopathy of renal significance; next-generation sequencing; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; The diagnostic approach of monoclonal gammopathy of renal significance is based on the detection of a monoclonal immunoglobulin in the blood and urine, and the identification of the underlying clone through bone marrow and/or peripheral blood cytologic and flow cytometry analysis. However, the monoclonal component and its corresponding clone may be undetectable using these routine techniques. Since clone identification is the cornerstone for guiding therapy and assessing disease response, more sensitive methods are required. We recently developed a high-throughput sequencing assay from bone marrow mRNA encoding immunoglobulins (RACE-RepSeq). This technique provides both full-length V(D)J region (variable, diversity and joining genes that generate unique receptors as antigen receptors) of the monoclonal immunoglobulin and the dominant immunoglobulin repertoire. This allows analysis of mutational patterns, immunoglobulin variable gene frequencies and diversity due to somatic hypermutation. Here, we evaluated the diagnostic performance of RACE-RepSeq in 16 patients with monoclonal-associated kidney lesions, and low serum monoclonal immunoglobulin and free light chain levels at diagnosis. Bone marrow immunohistochemical analysis was negative in all 11 patients so tested and 7 of 12 patients had no detectable clone matching the kidney deposits using flow cytometry analysis. By contrast, RACE-RepSeq detected a dominant clonal light chain sequence of matched isotype with respect to kidney deposits in all patients. Thus, high throughput mRNA sequencing appears highly sensitive to detect subtle clonal disorders in monoclonal gammopathy of renal significance and suggest this novel approach could help improve the management of this kidney disease. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/34767830; PUBMED: 34767830 |
| DOI: |
10.1016/j.kint.2021.10.017 |
| Availability: |
https://hal.science/hal-03482172; https://hal.science/hal-03482172v1/document; https://hal.science/hal-03482172v1/file/Javaugue%20et%20al-2021-RNA-based%20immunoglobulin%20repertoire%20sequencing%20is%20a%20new%20tool%20for%20the%20management.pdf; https://doi.org/10.1016/j.kint.2021.10.017 |
| Rights: |
http://creativecommons.org/licenses/by-nc/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.277BAF27 |
| Database: |
BASE |