T and B cell clonal expansion in Ras-associated lymphoproliferative disease (RALD) as revealed by next-generation sequencing

Clinical and Experimental Immunology
S Levy-MendelovichRaz Somech

Abstract

Ras-associated lymphoproliferative disease (RALD) is an autoimmune lymphoproliferative syndrome (ALPS)-like disease caused by mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) or neuroblastoma RAS viral (V-Ras) oncogene homologue (NRAS). The immunological phenotype and pathogenesis of RALD have yet to be studied extensively. Here we report a thorough immunological investigation of a RALD patient with a somatic KRAS mutation. Patient lymphocytes were analysed for phenotype, immunoglobulin levels and T cell proliferation capacity. T and B cell receptor excision circles (TREC and KREC, respectively), markers of naive T and B cell production, were measured serially for 3 years. T and B cell receptor repertoires were studied using both traditional assays as well as next-generation sequencing (NGS). TREC and KREC declined dramatically with time, as did T cell receptor diversity. NGS analysis demonstrated T and B clonal expansions and marked restriction of T and B cell receptor repertoires compared to healthy controls. Our results demonstrate, at least for our reported RALD patient, how peripheral T and B clonal expansions reciprocally limit lymphocyte production and restrict the lymphocyte receptor repertoire in this d...Continue Reading

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Citations

Jun 17, 2018·Clinical and Experimental Dermatology·A GiacamanA Martín-Santiago
Jan 31, 2019·Pediatric Blood & Cancer·Shanmuganathan ChandrakasanDavid Buchbinder
Feb 27, 2019·Journal of Pediatric Hematology/oncology·Luisa Cortellazzo WielAlberto Tommasini
Oct 5, 2020·Journal of Clinical Immunology·Quentin NevenBénédicte Brichard
Jan 20, 2021·International Reviews of Immunology·Maryam MohtashamiReza Yazdani
Mar 18, 2020·Genes & Diseases·Ankita SinghAmit Rawat
Oct 16, 2020·Journal of Veterinary Internal Medicine·Emily D RoutAnne C Avery
Feb 26, 2021·Current Hematologic Malignancy Reports·Jacob R Greenmyer, Mira Kohorst
Aug 28, 2021·Diagnostics·Maryam B KhadzhievaLyubov E Salnikova
Aug 30, 2021·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Riccardo PapaStefano Volpi
Jan 26, 2020·Blood Reviews·Sonia Meynier, Frédéric Rieux-Laucat

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