Immunoglobulin variable domain high-throughput sequencing reveals specific novel mutational patterns in POEMS syndrome

Autor: David Lavergne, Maria Victoria Ayala, Mehdi Alizadeh, Sébastien Bender, Virginie Pascal, Nathalie Gachard, Franck Bridoux, Alexis Saintamand, Arnaud Jaccard, Fabienne Auroy, Matthieu Filloux, Christophe Sirac, Vincent Javaugue, Michel Cogné
Přispěvatelé: 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), CHU Limoges, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement Français du Sang Bretagne, EFS, Plateforme de Biotechnologies Innovantes (PFBI), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), National Institutes of Health, National Heart, Lung, and Blood Institute United States Department of Health and Human ServicesNational Institutes of Health (NIH) - USA NIH National Heart Lung and Blood Institute (NHLBI) [HL68705], Ligue Nationale Contre le Cancer du Limousin, Fondation Francaise pour la Recherche contre le Myelome et les Gammapathies monoclonales, French Ministry of Research \'Plan maladies rares\', Fondation ARC pour la Recherche sur le Cancer Fondation ARC pour la Recherche sur le Cancer, Jonchère, Laurent, Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Blood
Blood, 2020, 135 (20), pp.1750-1758. ⟨10.1182/blood.2019004197⟩
Blood, American Society of Hematology, 2020, 135 (20), pp.1750-1758. ⟨10.1182/blood.2019004197⟩
ISSN: 0006-4971
1528-0020
DOI: 10.1182/blood.2019004197⟩
Popis: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare multisystem disease resulting from an underlying plasma cell (PC) dyscrasia. The pathophysiology of the disease remains unclear, but the role of the monoclonal immunoglobulin (Ig) light chain (LC) is strongly suspected because of the highly restrictive usage of 2 λ variable (V) domains (IGLV1-40 and IGLV1-44) and the general improvement of clinical manifestations after PC clone-targeted treatment. However, the diagnostic value of Ig LC sequencing, especially in the case of incomplete forms of the disease, remains to be determined. Using a sensitive high-throughput Ig repertoire sequencing on RNA (rapid amplification of cDNA ends-based repertoire sequencing [RACE-RepSeq]), we detected a λ LC monoclonal expansion in the bone marrow (BM) of 83% of patients with POEMS syndrome, including some in whom BM tests routinely performed to diagnose plasma cell dyscrasia failed to detect λ+ monoclonal PCs. Twenty-four (83%) of the 29 LC clonal sequences found were derived from the IGLV1-40 and IGLV1-44 germline genes, as well as 2 from the closely related IGLV1-36 gene, and all were associated with an IGLJ3*02 junction (J) gene, confirming the high restriction of VJ region usage in POEMS syndrome. RACE-RepSeq VJ full-length sequencing additionally revealed original mutational patterns, the strong specificity of which might crucially help establish or eliminate the diagnosis of POEMS syndrome in uncertain cases. Thus, RACE-RepSeq appears as a sensitive, rapid, and specific tool to detect low-abundance PC clones in BM and assign them to POEMS syndrome, with all the consequences for therapeutic options.
Databáze: OpenAIRE
Externí odkaz: