Reduced peripheral blood dendritic cell and monocyte subsets in MDS patients with systemic inflammatory or dysimmune diseases.
Dendritic cells
Inflammatory disease
Monocytes
Myelodysplastic syndrome
VEXAS syndrome
Journal
Clinical and experimental medicine
ISSN: 1591-9528
Titre abrégé: Clin Exp Med
Pays: Italy
ID NLM: 100973405
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
10
06
2022
accepted:
13
07
2022
medline:
23
6
2023
pubmed:
12
8
2022
entrez:
11
8
2022
Statut:
ppublish
Résumé
Systemic inflammatory and autoimmune diseases (SIADs) occur in 10-20% of patients with myelodysplastic syndrome (MDS). Recently identified VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, associated with somatic mutations in UBA1 (Ubiquitin-like modifier-activating enzyme 1), encompasses a range of severe inflammatory conditions along with hematological abnormalities, including MDS. The pathophysiological mechanisms underlying the association between MDS and SIADs remain largely unknown, especially the roles of different myeloid immune cell subsets. The aim of this study was to quantitatively evaluate peripheral blood myeloid immune cells (dendritic cells (DC) and monocytes) by flow cytometry in MDS patients with associated SIAD (n = 14, most often including relapsing polychondritis or neutrophilic dermatoses) and to compare their distribution in MDS patients without SIAD (n = 23) and healthy controls (n = 7). Most MDS and MDS/SIAD patients had low-risk MDS. Eight of 14 (57%) MDS/SIAD patients carried UBA1 somatic mutations, defining VEXAS syndrome.Compared with MDS patients, most DC and monocyte subsets were significantly decreased in MDS/SIAD patients, especially in MDS patients with VEXAS syndrome. Our study provides the first overview of the peripheral blood immune myeloid cell distribution in MDS patients with associated SIADs and raises several hypotheses: possible redistribution to inflammation sites, increased apoptosis, or impaired development in the bone marrow.
Sections du résumé
BACKGROUND
BACKGROUND
Systemic inflammatory and autoimmune diseases (SIADs) occur in 10-20% of patients with myelodysplastic syndrome (MDS). Recently identified VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, associated with somatic mutations in UBA1 (Ubiquitin-like modifier-activating enzyme 1), encompasses a range of severe inflammatory conditions along with hematological abnormalities, including MDS. The pathophysiological mechanisms underlying the association between MDS and SIADs remain largely unknown, especially the roles of different myeloid immune cell subsets. The aim of this study was to quantitatively evaluate peripheral blood myeloid immune cells (dendritic cells (DC) and monocytes) by flow cytometry in MDS patients with associated SIAD (n = 14, most often including relapsing polychondritis or neutrophilic dermatoses) and to compare their distribution in MDS patients without SIAD (n = 23) and healthy controls (n = 7). Most MDS and MDS/SIAD patients had low-risk MDS. Eight of 14 (57%) MDS/SIAD patients carried UBA1 somatic mutations, defining VEXAS syndrome.Compared with MDS patients, most DC and monocyte subsets were significantly decreased in MDS/SIAD patients, especially in MDS patients with VEXAS syndrome. Our study provides the first overview of the peripheral blood immune myeloid cell distribution in MDS patients with associated SIADs and raises several hypotheses: possible redistribution to inflammation sites, increased apoptosis, or impaired development in the bone marrow.
Identifiants
pubmed: 35953763
doi: 10.1007/s10238-022-00866-5
pii: 10.1007/s10238-022-00866-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
803-813Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Références
Adès L, Itzykson R, Fenaux P. Myelodysplastic syndromes. Lancet. 2014;383:2239–52.
pubmed: 24656536
Kordasti SY, et al. IL-17-producing CD4+T cells, pro-inflammatory cytokines and apoptosis are increased in low risk myelodysplastic syndrome. Br J Haematol. 2009;145:64–72.
pubmed: 19210506
Bouchliou I, et al. Th17 and Foxp3+ T regulatory cell dynamics and distribution in myelodysplastic syndromes. Clin Immunol. 2011;139:350–9.
pubmed: 21444247
Kordasti SY, et al. CD4+CD25high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS). Blood. 2007;110:847–50.
pubmed: 17412885
Kotsianidis I, et al. Kinetics, function and bone marrow trafficking of CD4+CD25+FOXP3+ regulatory T cells in myelodysplastic syndromes (MDS). Leukemia. 2009;23:510–8.
pubmed: 19020538
Kittang AO, et al. Expansion of myeloid derived suppressor cells correlates with number of T regulatory cells and disease progression in myelodysplastic syndrome. Oncoimmunology. 2016;5: e1062208.
pubmed: 27057428
Grignano E, et al. Autoimmune manifestations associated with myelodysplastic syndromes. Ann Hematol. 2018;97:2015–23.
pubmed: 30091023
Beck DB, et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med. 2020;383:2628–38.
pubmed: 33108101
pmcid: 7847551
Georgin-Lavialle S, et al. Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients. Br J Dermatol. 2021. https://doi.org/10.1111/bjd.20805 .
doi: 10.1111/bjd.20805
pubmed: 34632574
Breton G, et al. Human dendritic cells (DCs) are derived from distinct circulating precursors that are precommitted to become CD1c+ or CD141+ DCs. J Exp Med. 2016;213:2861–70.
pubmed: 27864467
pmcid: 5154947
Breton G, et al. Circulating precursors of human CD1c+ and CD141+ dendritic cells. J Exp Med. 2015;212:401–13.
pubmed: 25687281
pmcid: 4354370
Schlitzer A, et al. Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow. Nat Immunol. 2015;16:718–28.
pubmed: 26054720
Dzionek A, et al. BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. J Immunol. 2000;165:6037–46.
pubmed: 11086035
MacDonald KPA, et al. Characterization of human blood dendritic cell subsets. Blood. 2002;100:4512–20.
pubmed: 12393628
Robbins SH, et al. Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling. Genome Biol. 2008;9:R17.
pubmed: 18218067
pmcid: 2395256
Ziegler-Heitbrock L, et al. Nomenclature of monocytes and dendritic cells in blood. Blood. 2010;116:e74–80.
pubmed: 20628149
Cros J, et al. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity. 2010;33:375–86.
pubmed: 20832340
pmcid: 3063338
Wong KL, et al. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood. 2011;118:e16–31.
pubmed: 21653326
Zawada AM, et al. SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset. Blood. 2011;118:e50–61.
pubmed: 21803849
Schäkel K, et al. Human 6-Sulfo LacNAc-expressing dendritic cells are principal producers of early interleukin-12 and are controlled by erythrocytes. Immunity. 2006;24:767–77.
pubmed: 16782032
Schäkel K, et al. A novel dendritic cell population in human blood: one-step immunomagnetic isolation by a specific mAb (M-DC8) and in vitro priming of cytotoxic T lymphocytes. Eur J Immunol. 1998;28:4084–93.
pubmed: 9862344
Schäkel K, et al. 6-Sulfo LacNAc, a novel carbohydrate modification of PSGL-1, defines an inflammatory type of human dendritic cells. Immunity. 2002;17:289–301.
pubmed: 12354382
van Leeuwen-Kerkhoff N, et al. Human bone marrow-derived myeloid dendritic cells show an immature transcriptional and functional profile compared to their peripheral blood counterparts and separate from slan+ non-classical monocytes. Front Immunol. 2018;9:1619.
pubmed: 30061890
pmcid: 6055354
van Leeuwen-Kerkhoff N, et al. Transcriptional profiling reveals functional dichotomy between human Slan+non-classical monocytes and myeloid dendritic cells. J Leukoc Biol. 2017;102:1055–68.
pubmed: 28720687
Hofer TP, et al. slan-defined subsets of CD16-positive monocytes: impact of granulomatous inflammation and M-CSF receptor mutation. Blood. 2015;126:2601–10.
pubmed: 26443621
Braun T, Fenaux P. Myelodysplastic syndromes (MDS) and autoimmune disorders (AD): cause or consequence? Best Pract Res Clin Haematol. 2013;26:327–36.
pubmed: 24507810
Sallman DA, List A. The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes. Blood. 2019;133:1039–48.
pubmed: 30670444
pmcid: 7022316
Zhao LP, et al. Genomic landscape of MDS/CMML associated with systemic inflammatory and autoimmune disease. Leukemia. 2021;35:2720–4.
pubmed: 33623140
Van Leeuwen-Kerkhoff N, et al. Reduced frequencies and functional impairment of dendritic cell subsets and non-classical monocytes in myelodysplastic syndromes. Haematologica. 2021. https://doi.org/10.3324/haematol.2020.268136 .
doi: 10.3324/haematol.2020.268136
pmcid: 8883570
Gill MA, et al. Blood dendritic cells and DC-poietins in systemic lupus erythematosus. Hum Immunol. 2002;63:1172–80.
pubmed: 12480261
Robak E, Smolewski P, Woźniacka A, Sysa-Jedrzejowska A, Robak T. Clinical significance of circulating dendritic cells in patients with systemic lupus erythematosus. Mediat Inflamm. 2004;13:171–80.
Scheinecker C, Zwlfer B, Kller M, Mnner G, Smolen JS. Alterations of dendritic cells in systemic lupus erythematosus: phenotypic and functional deficiencies. Arthritis Rheum. 2001;44:856–65.
pubmed: 11315925
Migita K, et al. Reduced blood BDCA-2+ (lymphoid) and CD11c+ (myeloid) dendritic cells in systemic lupus erythematosus. Clin Exp Immunol. 2005;142:84–91.
pubmed: 16178860
pmcid: 1809479
Fiore N, et al. Immature myeloid and plasmacytoid dendritic cells infiltrate renal tubulointerstitium in patients with lupus nephritis. Mol Immunol. 2008;45:259–65.
pubmed: 17570528
Jin O, et al. Systemic lupus erythematosus patients have increased number of circulating plasmacytoid dendritic cells, but decreased myeloid dendritic cells with deficient CD83 expression. Lupus. 2008;17:654–62.
pubmed: 18625638
Henriques A, et al. Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus. Rheumatol Int. 2012;32:863–9.
pubmed: 21221593
Gerl V, et al. Blood dendritic cells in systemic lupus erythematosus exhibit altered activation state and chemokine receptor function. Ann Rheum Dis. 2010;69:1370–7.
pubmed: 19854711
Tucci M, et al. Glomerular accumulation of plasmacytoid dendritic cells in active lupus nephritis: role of interleukin-18. Arthritis Rheum. 2008;58:251–62.
pubmed: 18163476
Olaru F, et al. Intracapillary immune complexes recruit and activate slan-expressing CD16+ monocytes in human lupus nephritis. JCI Insight. 2018;3: e96492.
pubmed: 29875315
pmcid: 6124405
Zakine E, et al. UBA1 variations in neutrophilic dermatosis skin lesions of patients with VEXAS syndrome. JAMA Dermatol. 2021;157:1349–54.
pubmed: 34495287
Mékinian A, et al. A phase II study of the efficacy and tolerance of azacytidine (AZA) in steroid dependent/refractory systemic autoimmune and inflammatory disorders (SAID) associated with MDS or CMML (GFM- AZA-SAID -trial). Blood. 2021;138:3697.
Arber DA, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.
pubmed: 27069254
Greenberg PL, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120:2454–65.
pubmed: 22740453
pmcid: 4425443
Pfeilstöcker M, et al. Time-dependent changes in mortality and transformation risk in MDS. Blood. 2016;128:902–10.
pubmed: 27335276
pmcid: 5161006