En analysant la moelle osseuse de 113 patients atteints de SMD, ainsi que de 53 personnes sans SMD servant de témoins, les chercheurs ont identifiés deux familles de Tregs grâce à deux marqueurs de surface, CD95 et CD45RA. La première famille correspond à des Tregs "naïfs", plutôt inactifs. La seconde, baptisée Tregs CD95⁺/CD45RA⁻, regroupe des cellules très activées et fortement immunosuppressives, déjà repérées auparavant dans une autre maladie de la moelle, l'aplasie médullaire.
By analyzing the bone marrow of 113 MDS patients, as well as 53 people without MDS serving as controls, the researchers identified two Treg families using two surface markers, CD95 and CD45RA. The first corresponds to "naïve," largely inactive Tregs. The second, named CD95⁺/CD45RA⁻ Tregs, comprises highly activated and strongly immunosuppressive cells, previously identified in another bone marrow disease, aplastic anemia.
In this study, the overall quantity of Tregs did not differ between MDS patients and controls, regardless of disease stage. In contrast, the proportion of CD95⁺/CD45RA⁻ Tregs was higher in MDS patients from the time of diagnosis, and increased further in more severe forms, suggesting a progressive accumulation of these highly immunosuppressive cells in the marrow as the disease evolves. This accumulation continued over time in patients whose disease was worsening, but remained stable in those who responded well to treatment with hypomethylating agents (drugs such as azacitidine, which today constitute the reference treatment for higher-risk forms of MDS and which act by modifying gene expression in abnormal marrow cells). Conversely, a low level of these Tregs was associated with mutations in genes called TET2/IDH and with the presence of associated autoimmune diseases. The most striking result remains that patients with a high level of these Tregs at study entry had a significantly higher risk of disease progression, with reduced progression-free survival, and this independently of the prognostic scores already used in the clinic, the IPSS-R and the IPSS-M. These two scores currently serve as the reference for classifying patients by risk: the IPSS-R combines blood parameters, the percentage of abnormal cells in the marrow, and chromosomal abnormalities, while the more recent IPSS-M also adds genetic mutations identified by sequencing.
This work therefore suggests that, in addition to the classic prognostic scores based on genetics and blood parameters, measuring this specific Treg subtype in the bone marrow could help better identify, from the time of diagnosis, patients at risk of rapid progression — particularly those classified as low risk but who in fact progress faster than expected. This could also help better target patients who are, or are not, likely to benefit from immunosuppressive treatment. The authors nonetheless remain cautious and emphasize that the study concerns relative proportions of cells rather than absolute counts, with some analyzed subgroups remaining modest in size. Further studies, particularly on peripheral blood rather than bone marrow, will be needed to confirm and refine these results.
Ce travail suggère donc qu'en complément des scores pronostiques classiques, fondés sur la génétique et les paramètres sanguins, mesurer ce sous-type précis de Tregs dans la moelle osseuse pourrait aider à mieux identifier, dès le diagnostic, les patients à risque de progression rapide, notamment ceux classés à faible risque mais qui évoluent en réalité plus vite que prévu. Cela pourrait également permettre de mieux cibler les patients susceptibles, ou non, de bénéficier d'un traitement immunosuppresseur. Les auteurs restent toutefois prudents et soulignent que l'étude porte sur des proportions relatives de cellules, et non sur des comptes absolus, certains sous-groupes analysés restant de taille modeste. Des études complémentaires, notamment sur le sang périphérique plutôt que sur la moelle osseuse, seront nécessaires pour confirmer et affiner ces résultats.

Reference of the article:

High frequency of CD95+/CD45RA- regulatory T cells defines an immunosuppressive profile associated with MDS progression. 
Vazquez R, Deredec N, Boussaid I, Boncoeur P, Knosp C, Houvert A, Zalmai L, Friedrich C, Almire C, Dussiau C, Willems L, Birsen R, Decroocq J, Bouscary D, Kosmider O, Kordasti S, Fontenay M, Simoni Y, Chapuis N. 
Br J Haematol. 2026 Jun;208(6):1993-2003

Comment on the article:

Selig M, Penter L. Not all Tregs in MDS are created equal. Br J Haematol. 2026 Jun;208(6):2332-2334. doi: 10.1111/bjh.70503. Epub 2026 Apr 23. PMID: 42025585.