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Reduced peripheral blood dendritic cell and monocyte subsets in MDS patients with systemic inflammatory or dysimmune diseases

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Abstract

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.

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Abbreviations

AML:

Acute myeloid leukemia

ANSM:

Agence Nationale de Sécurité du Médicament

AZA:

Azacitidine

CD:

Cluster of differentiation

cDC:

Conventional myeloid dendritic cells

cDC1:

Conventional myeloid dendritic cells 1

cDC2:

Conventional myeloid dendritic cells 2

CMML:

Chronic myelomonocytic leukemia

cMo:

Classical monocytes

DC:

Dendritic cells

EDTA:

Ethylenediaminetetraacetic acid

PBMC:

Peripheral blood mononuclear cells

GFM:

Groupe Francophone des Myélodysplasies

IPSS:

International prognostic scoring system

MDS:

Myelodysplastic syndrome

MINHEMON:

French Network of dysimmune disorders associated with hemopathies

Mo:

Monocytes

ncMo:

Nonclassical monocytes

iMo:

Intermediate monocytes

pDC:

Plasmacytoid dendritic cells

R-IPSS:

Revised international prognostic scoring system

SD:

Standard deviation

SIAD:

Systemic inflammatory and autoimmune disease

slan Mo:

Slan + nonclassical monocytes.

slanDC:

6-Sulfo LacNAc dendritic cells

SLE:

Systemic lupus erythematosus

UBA1:

Ubiquitin-like modifier-activating enzyme 1

UBA1-WT:

Wild-type UBA1

VEXAS:

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic

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Acknowledgements

We thank Frédéric de Vassoigne for his help in collecting patient samples (Tumorothèque Saint-Antoine, APHP, Hôpital Saint-Antoine, Paris, France).

Funding

There was no funding for this research.

Author information

Author notes

  1. Béatrice Gaugler and Arsène Mekinian have contributed equally.

Authors and Affiliations

  1. Sorbonne Université, INSERM UMR938, Centre de Recherche Saint-Antoine (CRSA), 75012, Paris, France

    Vincent Jachiet, Laure Ricard, Florent Malard, Mohamad Mohty, Béatrice Gaugler & Arsène Mekinian

  2. Service de Médecine Interne et Inflammation-Immunopathology-Biotherapy Department (DMU i3), Sorbonne Université, AP-HP, Hôpital Saint Antoine, Paris, France

    Vincent Jachiet, Olivier Fain & Arsène Mekinian

  3. Service d’Hématologie Clinique et de Thérapie Cellulaire, Sorbonne Université, AP-HP, Hôpital Saint Antoine, Paris, France

    Laure Ricard, Florent Malard, Anne Vekhoff, Mohamad Mohty & Béatrice Gaugler

  4. Service d’Hématologie Biologique, Sorbonne Université, AP-HP, Hôpital Saint Antoine, Paris, France

    Pierre Hirsch

  5. Service d’Oncologie et d’Hématologie, Hôpital Saint Vincent de Paul, Université Catholique de Lille, Lille, France

    Laurent Pascal

  6. Service de Médecine Interne, CHU de Toulouse, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France

    Odile Beyne-Rauzy

  7. Service d’Hématologie Clinique, CHU de Nantes, Nantes, France

    Pierre Peterlin

  8. Service de Médecine Interne, maladies multi-organiques de l’adulte, Hôpital Saint-Éloi, CHU de Montpellier, Université de Montpellier, Montpellier, France

    Alexandre Thibault Jacques Maria

  9. Institut Paoli-Calmettes, CRCM, Aix-Marseille Univ, Inserm, CNRS, Marseille, France

    Norbert Vey

  10. Service d’Hématologie et de Médecine Interne, Hôpital Brabois, CHRU Nancy, Nancy, France

    Maud D’Aveni

  11. Service d’Hématologie Clinique et de Thérapie Cellulaire, Hôpital Dupuytren, CHU de Limoges, Limoges, France

    Marie-Pierre Gourin

  12. Service d’Hématologie et de Thérapie Cellulaire, CHU Haut-Lévêque, Bordeaux, France

    Sophie Dimicoli-Salazar

  13. Service d’Hématologie Clinique, Centre Hospitalier Côte Basque, Bayonne, France

    Anne Banos

  14. Service d’Hématologie Clinique, Hôpital Universitaire Carémeau, Institut de Cancérologie du Gard, Nîmes, France

    Stefan Wickenhauser

  15. Service de Médecine Interne et Immunologie Clinique, CHU Lille, 59000, Lille, France

    Louis Terriou

  16. Service d’Hématologie Clinique, Hôpital Estaing, CHU de Clermont-Ferrand, Clermont-Ferrand, France

    Benoit De Renzis

  17. Service d’Hématologie Clinique, Hôpital Robert Debré, CHU de Reims, Reims, France

    Eric Durot

  18. Service d’Hématologie, Institut de Cancérologie Strasbourg Europe (ICANS), 17 rue Albert Calmette, Strasbourg, France

    Shanti Natarajan-Ame

  19. Service d’Hématologie et Oncologie, CH William Morey, Chalon sur Saône, France

    Laurent Voillat

  20. Service d’Hématologie, Université Grenoble Alpes Et CHU Grenoble Alpes, Grenoble, France

    Sophie Park

  21. Service de Médecine Interne, CH William Morey, Chalon sur Saône, France

    Julien Vinit

  22. Service de Médecine Interne et Hématologie, GHLA, CH de Rochefort, Rochefort, France

    Céline Dieval

  23. Service de Rhumatologie, Hôpital Montfermeil, Montfermeil, France

    Azeddine Dellal

  24. Service de Médecine Interne, CHU Estaing, Clermont-Ferrand, France

    Vincent Grobost

  25. Service d’Hématologie, AP-HP, Hôpital Cochin, Paris, France

    Lise Willems

  26. Service d’Hématologie Adultes, AP-HP, Hôpital Necker-Enfants Malades, 75015, Paris, France

    Julien Rossignol

  27. Département d’Hématologie, Institut Gustave Roussy, Villejuif, France

    Eric Solary

  28. Service d’Hématologie Biologique, Université de Paris, AP-HP, Hôpital Cochin, 75014, Paris, France

    Olivier Kosmider

  29. Institut de Recherche Saint Louis, Hôpital Saint Louis, Université de Paris, INSERM U1160, Paris, France

    Nicolas Dulphy

  30. Département d’Hématologie, Université de Paris, AP-HP, Hôpital Saint Louis, 75010, Paris, France

    Lin Pierre Zhao, Lionel Adès & Pierre Fenaux

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  1. Vincent Jachiet
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Consortia

MINHEMON: French Network of dysimmune disorders associated with hemopathies

Contributions

All coauthors were involved in study design, sample collection, conducting experiments, analyzing results, drafting the manuscript, and approving the final manuscript prior to submission.

Corresponding author

Correspondence to Vincent Jachiet.

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Conflict of interest

AM is investigator of CELGENE, ROCHE, CHUGAI founded trials with APHP and Hopital 15–20 promotion; AM received several fees for congress travels and experts’ use from LFB, SANOFI, SHIRE, and CELGENE. The other authors declare no conflict of interest.

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All participants provided written informed consent. The study was approved by the local institutional review board (EudraCT 2016-000918-30, ANSM (Agence Nationale de Sécurité du Médicament) 160580A-11, registration date 26-AUG-2016) and in accordance with the Declaration of Helsinki.

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Jachiet, V., Ricard, L., Hirsch, P. et al. Reduced peripheral blood dendritic cell and monocyte subsets in MDS patients with systemic inflammatory or dysimmune diseases. Clin Exp Med 23, 803–813 (2023). https://doi.org/10.1007/s10238-022-00866-5

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