Successful identification of predictive profiles for infection utilising systems-level immune analysis: a pilot study in patients with relapsed and refractory multiple myeloma.
CyTOF
RNAseq
immune profiling
infection risk prediction
multiple myeloma
Journal
Clinical & translational immunology
ISSN: 2050-0068
Titre abrégé: Clin Transl Immunology
Pays: Australia
ID NLM: 101638268
Informations de publication
Date de publication:
2021
2021
Historique:
received:
17
09
2020
revised:
18
11
2020
accepted:
14
12
2020
entrez:
13
1
2021
pubmed:
14
1
2021
medline:
14
1
2021
Statut:
epublish
Résumé
Patients with multiple myeloma (MM) are at increased risk for infection. Clinical assessment of infection risk is increasingly challenging in the era of immune-based therapy. A pilot systems-level immune analysis study to identify predictive markers for infection was conducted. Patients with relapsed and/or refractory MM (RRMM) who participated in a treatment trial of lenalidomide and dexamethasone were evaluated. Data on patient demographics, disease and episodes of infection were extracted from clinical records. Peripheral blood mononuclear cells (PBMCs) collected at defined intervals were analysed, with or without mitogen re-stimulation, using RNA sequencing and mass cytometry (CyTOF). CyTOF-derived cell subsets and RNAseq gene expression profiles were compared between patients that did and did not develop infection to identify immune signatures that predict infection over a 3-month period. Twenty-three patients participated in the original treatment trial, and we were able to access samples from 17 RRMM patients for further evaluation in our study. Nearly half the patients developed an infection (8/17) within 3 months of sample collection. Infections were mostly clinically diagnosed (62.5%), and the majority involved the respiratory tract (87.5%). We did not detect phenotypic or numerical differences in immune cell populations between patients that did and did not develop infections. Transcriptional profiling of stimulated PBMCs revealed distinct Th2 immune pathway signatures in patients that developed infection. Immune cell counts were not useful predictors of infection risk. Functional assessment of stimulated PBMCs has identified potential immune profiles that may predict future infection risk in patients with RRMM.
Identifiants
pubmed: 33437482
doi: 10.1002/cti2.1235
pii: CTI21235
pmc: PMC7790592
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e1235Informations de copyright
© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
J Exp Med. 2019 Mar 4;216(3):482-500
pubmed: 30755454
Immunity. 2003 Nov;19(5):739-48
pubmed: 14614860
Bioinformatics. 2005 May 1;21(9):2067-75
pubmed: 15657102
Exp Hematol. 2018 Sep;65:49-56
pubmed: 29885947
Ann Appl Stat. 2016 Jun;10(2):946-963
pubmed: 28367255
BMC Bioinformatics. 2006 May 19;7:261
pubmed: 16712727
Genome Biol. 2010;11(3):R25
pubmed: 20196867
Eur J Haematol. 2017 Feb;98(2):149-153
pubmed: 27717026
Eur J Haematol. 2019 Feb;102(2):182-190
pubmed: 30485563
Virology. 2019 Jan 2;526:155-164
pubmed: 30390564
Cell Rep. 2017 Aug 29;20(9):2238-2250
pubmed: 28854371
J Virol. 2014 Sep 1;88(17):10214-27
pubmed: 24965449
Nat Rev Drug Discov. 2008 Sep;7(9):759-70
pubmed: 18758473
Br J Haematol. 2015 Oct;171(1):100-8
pubmed: 26105211
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Blood. 2011 Feb 3;117(5):1605-13
pubmed: 20978269
Cell Host Microbe. 2014 Nov 12;16(5):616-26
pubmed: 25525793
Sci Immunol. 2019 Nov 15;4(41):
pubmed: 31732517
Front Immunol. 2017 Oct 05;8:1247
pubmed: 29051761
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Ann Hematol. 2018 Nov;97(11):2163-2171
pubmed: 29938309
J Infect Dis. 1990 Mar;161(3):397-401
pubmed: 2179421
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Nucleic Acids Res. 2019 May 7;47(8):e47
pubmed: 30783653
Blood Rev. 2014 Mar;28(2):75-86
pubmed: 24582081
Mucosal Immunol. 2018 Jan;11(1):209-219
pubmed: 28513592
Immunology. 2005 Apr;114(4):459-60
pubmed: 15804281
Immunity. 2000 Dec;13(6):805-15
pubmed: 11163196
Br J Haematol. 2017 May;177(3):441-448
pubmed: 28197996