Autoimmune and autoinflammatory diseases
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Myeloid disorders and inflammatory manifestations

Myelodysplastic syndromes and chronic myelomonocytic leukaemia are bone marrow diseases which, in some patients, come with inflammatory or autoimmune manifestations. Arsène Mekinian's work on this subject measures how these manifestations present, how they respond to treatment, and what happens when the marrow clone itself is targeted.

What are the inflammatory manifestations associated with myeloid haematological disorders?

Myelodysplastic syndromes and chronic myelomonocytic leukaemia are diseases of the bone marrow. A group of stem cells carrying acquired abnormalities takes over and produces blood cells in insufficient number or of insufficient quality. The result is anaemia, repeated infections or bleeding. These diseases occur mainly in adults after the age of sixty. Chronic myelomonocytic leukaemia occupies an intermediate position between the myelodysplastic syndromes and the diseases in which the marrow produces too many cells.

In some of these patients, inflammatory or autoimmune manifestations are added: inflammation of the vessel wall, arthritis, inflammation of the cartilage of the ear or the nose, skin eruptions rich in neutrophils, repeated fevers. These manifestations sometimes precede the diagnosis of the haematological disease by several years and often respond poorly to the usual treatments for inflammation. The question raised by this association is whether the inflammation arises from the abnormal marrow clone, and therefore whether treating the marrow treats the inflammation. It belongs both to internal medicine and to haematology, which is why work in this field is conducted by the two specialties together.

His work on this subject

The study that structured this field in France is a multicentre retrospective study published in Rheumatology (Oxford) in 2016, of which Arsène Mekinian is 1st of 40 named authors. It analysed 123 patients with a myelodysplastic syndrome and an associated systemic inflammatory or autoimmune disease, and compared them with 665 patients with a myelodysplastic syndrome or chronic myelomonocytic leukaemia without any such manifestation. Mean age was 70 years and the male to female ratio was 2. The manifestations were systemic vasculitis in 39 cases (32%), connective tissue disease in 31 cases (25%), inflammatory arthritis in 28 cases (23%), neutrophilic dermatosis in 12 cases (10%), and remained unclassified in 13 cases (11%). A significant association was shown between chronic myelomonocytic leukaemia and systemic vasculitis (P = 0.0024). One hundred and eighteen patients (96%) were treated, 91% of them with corticosteroids; the response to first-line treatment was 83%, and 80% for corticosteroids alone, but a second line was needed in 48% of cases for steroid dependence or relapse. Compared with the 665 patients without a systemic manifestation, patients who had one were younger, more often men, and more often had an unfavourable karyotype (16% versus 11%, P = 0.04), with no difference in overall survival between the two groups (P = 0.5). The article was published online in September 2015, before the MINHEMON association was declared in 2016; it therefore predates the club and cannot be attributed to it. 1

The continuation of this work addressed the idea of treating the inflammatory manifestation by treating the marrow. A retrospective series of 22 patients published in Leukemia Research in 2016, of which he is 2nd of 21 named authors, observed a response of the autoimmune disease to azacitidine in 19 patients (86%), a reduction or withdrawal of corticosteroids or immunosuppressants in 16 (73%) and a haematological response in 55% of patients; the course of the haematological disease and that of the autoimmune disease were concordant in 13 cases (59%). 2 This retrospective observation led to a prospective phase 2 trial, GFM-AZA-SAID, registered under the number NCT02985190, sponsored by the Groupe francophone des myélodysplasies with Celgene as industry collaborator, open in 59 French centres, which enrolled 30 patients between 26 January 2017 and 30 August 2022, and of which Arsène Mekinian is principal investigator. The trial is completed and it has been published: a letter that appeared in Leukemia in 2022, of which he is 1st of 36 named authors and corresponding author. 9 Its overall numerical results are not given here: no results are posted on the registry, and the results section of the letter is not open access. One partial figure is available at source: a letter published in Haematologica in 2025, which he co-signs as 12th of 13 named authors, reports that, in the AZA-SAID trial, 9 of 12 patients with VEXAS syndrome responded to azacitidine, with a median follow-up of 19 months. 12

The immunomodulatory side was assessed in parallel. A French multicentre retrospective study published in Autoimmunity Reviews in 2017, of which he is 1st of 29 named authors and corresponding author, covered 29 patients treated with at least one biologic. Across the 114 treatment lines analysed over a median follow-up of three years, the overall response was 54%; it was more frequent with corticosteroids (78%) and with rituximab (66%) than with conventional disease-modifying treatment (45%) or with the other biologics (33%), with a p below 0.05. Twenty of the 29 patients (71%) had at least one severe infection during follow-up, which is the counterpart of these treatments in this elderly and cytopenic population. 3 Another approach, low-dose interleukin 2, was explored in three steroid-dependent patients refractory to biologics or to azacitidine, in a case report published in Rheumatology (Oxford) in 2021 of which he is 8th of 9 named authors: clinical improvement and steroid sparing were obtained in 2 of the 3 patients, without serious adverse events. A report of three cases allows no general conclusion. 6

The network has built a retrospective database, named in the publications, which has made it possible to describe particular manifestations. A case-control study published in Clinical and Experimental Rheumatology in 2022, conducted according to its abstract on the French retrospective database of the MINHEMON network and of which he is 54th and last of 54 named authors, compared 35 patients who had had a venous thromboembolic event with 127 who had not, a frequency of 21.6%; 8 of the 35 (22.9%) had at least two episodes, and bleeding occurred in 19.4% of anticoagulated patients (6 of 31). On multivariate analysis, only progression of the haematological disease at the time of the event was associated with thrombosis (odds ratio 28.82, 95% confidence interval 5.52 to 530.70), the very wide interval of this estimate limiting its scope. Neither overall survival (p = 0.68) nor leukaemia-free survival (p = 0.83) differed between the two groups. 10 Two other manifestations have been the subject of dedicated studies. In Haematologica in 2021, where he is 28th and last of 28 named authors, 41 patients with immune thrombocytopenia associated with a myelodysplastic syndrome or with chronic myelomonocytic leukaemia were compared with patients with isolated immune thrombocytopenia: the thrombocytopenia was chronic in 26 (63%), the myelodysplasia was low risk in 30 (73%), chronic myelomonocytic leukaemia was present in 24 (59%) and an associated autoimmune disease in 10 (24%); severe bleeding was more frequent at comparable platelet counts, 4 patients (10%) had a multirefractory form compared with none in the control group, and after a median follow-up of 60 months overall survival did not differ. 5 In Seminars in Arthritis and Rheumatism in 2021, where he is 4th of 14 named authors, 21 cases of inflammatory myopathy associated with a myelodysplastic syndrome were assembled, 11 French cases and 10 drawn from a literature review: dermatomyositis was the most frequent form (59%), anti-TIF1 gamma antibodies were present in 24% of patients compared with 4% in the comparison group (p = 0.0039), no antisynthetase syndrome was observed (0% versus 28%, p = 0.01), the myopathy was steroid-sensitive in 82% of patients but steroid-dependent in 56%, and overall survival was poorer than in the absence of an associated myelodysplastic syndrome (p = 0.0002). 7

The most recent phase of this work is genetic. In 2019, a case published in Haematologica, of which he is 10th of 16 named authors, described in the same patient an Erdheim-Chester disease and a chronic myelomonocytic leukaemia carrying the same clonal mutation; this is an isolated case. 14 In 2021, a letter that appeared in Leukemia, of which he is 15th of 21 named authors, looked for mutations of the UBA1 gene, those that define VEXAS syndrome, in patients with a myelodysplastic syndrome or chronic myelomonocytic leukaemia with an associated systemic disease; this letter has no indexed abstract and its text is not open access, so its figures are not reproduced here. 8 In 2026, a case-control study published in JAMA Dermatology, of which he is 24th of 25 named authors, brought together 24 patients with lupus-like manifestations associated with a myelodysplastic syndrome or with chronic myelomonocytic leukaemia, including 19 systemic lupus and 5 cutaneous lupus, of median age 65 years (range 32 to 85), 15 men (63%) and 9 women (38%), collected from January 1975 to January 2023 and followed for a median of 4.5 years. Cutaneous involvement was the most frequent manifestation (17 patients, 71%), chilblain lupus being its predominant subtype (6, 35%); the underlying haematological disease was a myelodysplastic syndrome in 16 (66%) and chronic myelomonocytic leukaemia in 8 (34%), lower risk in 22 cases (92%). Compared with idiopathic systemic lupus, these patients were older (65 years versus 23 years, P below 0.001), more often men (10 [53%] versus 3 [8%], P = 0.008), had less renal involvement (2 [10%] versus 27 [71%], P below 0.001), less joint involvement (7 [36%] versus 37 [97%], P below 0.001) and less often anti-double-stranded DNA antibodies (6 [32%] versus 29 [76%], P = 0.001). Central review of the skin biopsies reclassified 6 (50%) as cutaneous involvement by the myeloid clone, the same myeloid variants were found in blood and in skin in 6 of 8 patients, and treatment directed against the clone, azacitidine or allogeneic haematopoietic stem cell transplantation, was followed by a joint haematological and lupus response in 5 of 7 patients. The authors conclude that this is a distinct entity, arising from clonal inflammation rather than from classical autoimmunity. 13

This work is carried by a network. Arsène Mekinian states that he founded the MINHEMON club in 2016, devoted to the systemic manifestations of haematological malignancies, and that he chairs it; no public source consulted names the officers of the association, and this point therefore reads as information he gives himself. The published existence of the network is verifiable: MINHEMON appears as an author group in the consortium field of the MEDLINE record of six of the works cited here, under variable wordings, including "GFM, SNFMI, CRI and MINHEMON" in 2017 and "EMSED Group and MINHEMON Group" in 2026. A national ambispective observational cohort has also been registered under the number NCT05969821, entitled Clonal Hematopoiesis of Immunological Significance: it is sponsored by AP-HP (Assistance Publique – Hôpitaux de Paris), with Sorbonne Université, Inserm and the MINHEMON club as declared collaborators, it plans 5,000 participants with an estimated start in April 2026 and an estimated primary completion in April 2036, and Arsène Mekinian is declared principal investigator. As of 8 September 2026, this cohort is not open to recruitment and has produced no results.

Where care is organised

Arsène Mekinian works in the department of internal medicine of Saint-Antoine Hospital (AP-HP, Sorbonne Université), attached to the medical and university department devoted to inflammation, immunopathology and biotherapies, designated DHU i2B until about 2019, then DMU 3iD and DMU i3 in the affiliations of his publications. This is the affiliation that appears on his MEDLINE records for all the works cited on this page.

These situations call for a joint decision between internal medicine and haematology. A national MINHEMON multidisciplinary team meeting, accredited by the FAI²R rare disease network, is devoted to the systemic manifestations of haematological malignancies: VEXAS syndrome, myelodysplastic syndromes, chronic myelomonocytic leukaemias, clonal haematopoiesis, monoclonal gammopathies, lymphoid malignancies and myeloproliferative neoplasms. It brings together internists, haematologists, biologists and dermatologists to discuss complex cases and to settle diagnostic and therapeutic directions collectively. It is held by videoconference, on Tuesdays from 17:00 to 18:00, roughly every two weeks. The expert quorum published by the network numbers 24 doctors, among them Arsène Mekinian for internal medicine. Each case is presented by the doctor who follows the patient, with an information form sent in advance according to the arrangements set out by the network. This meeting is intended for doctors and is not a route to consultation. These details were recorded on 8 September 2026 on the FAI²R website.

What is not known

The frequency of these manifestations is not itself established, and his own texts give different orders of magnitude. A review published in Annals of Hematology in 2018, of which he is 6th and last of 6, writes that autoimmune diseases concern 10 to 20% of patients with a myelodysplastic syndrome. 4 The 2021 study on immune thrombocytopenia repeats 10 to 20%. 5 The 2022 study on venous thromboembolism writes 10 to 30%. 10 The introduction to the letter published in Leukemia in 2022 writes 15 to 25%. 9 The review in French published in the Bulletin du Cancer in 2023, of which he is 7th and last of 7, writes "up to a quarter" of patients. 11 These differences follow from the populations studied and the definitions used, and no single figure can be presented as the frequency of these manifestations.

The nature of the available evidence limits what can be drawn from it. With the exception of the GFM-AZA-SAID trial, all the works cited here are retrospective, without a control arm, cover a few dozen patients, and use response criteria for the inflammatory manifestation that are not standardised from one study to another. The trial itself enrolled 30 patients, without a comparator, and its detailed results are not freely accessible; no results are posted on ClinicalTrials.gov. What is known of the effect of azacitidine on these manifestations therefore rests on one uncontrolled phase 2 trial and on retrospective series.

Two of his texts do not say the same thing about the 2016 series of 22 patients. The abstract of the Leukemia Research article reports a response of the autoimmune disease in 19 of 22 patients and a reduction or withdrawal of corticosteroids or immunosuppressants in 16 of them. 2 The introduction to the letter published in Leukemia in 2022, which cites this same article, describes a steroid-sparing effect in 19 of 22 patients. 9 This difference of reading is not settled here.

It is not known whether treating the manifestation alters the course of the haematological disease. The 2016 study showed no difference in overall survival between patients with and without a systemic manifestation. 1 The study on immune thrombocytopenia found better leukaemia-free survival in patients who had one than in patients without thrombocytopenia. 5 The study on inflammatory myopathies found poorer survival when a myelodysplastic syndrome was associated. 7 These three results concern different populations and different questions; none of them allows a conclusion about the effect of treatment.

It is not known how to predict which patients will develop these manifestations. Nor is it known in what order to combine treatment directed against the clone with immunomodulatory treatment, or in which patients to favour one or the other: the 2023 review in French raises the question without settling it, noting both the frequent steroid dependence and the poor tolerance of conventional immunosuppressants in this population. 11 The role of somatic mutations other than those of the UBA1 gene is not established. The CHIS cohort, registered under the number NCT05969821, is intended to document these questions; it is not open to recruitment and has produced no data.

Two points outside his own work place this field. The initial description of VEXAS syndrome, by Beck and colleagues in the New England Journal of Medicine in 2020, gave a genetic explanation for part of these situations; this work is not his. The terminology has also changed over the period covered by these studies, to the point that his own 2023 review is indexed in English under the term "myelodysplastic neoplasms" and in French under "syndromes myélodysplasiques"; comparing series published ten years apart therefore requires checking what each one counts. 11

Sources and method

Every publication listed below was checked on 14 September 2026 on its full MEDLINE record, opened in the PubMed `?format=pubmed` display. Author positions are counted on the `FAU` fields alone, that is, on the named authors of the article; the `CN`, `FIR` and `IR` fields, which carry the name of a collaborative group and the list of its collaborators, never count as an author position. The surname appears in MEDLINE under two spellings, with and without an acute accent: on this page three records write it without the accent, those of 2017 3, of 2021 on interleukin 2 6 and of 2026 13. Where a record carries neither an indexed abstract nor an open-access full text, the work is cited by its title, its type and his author position, with no figure. Figures, tables and passages from articles under copyright are not reproduced.

References

Published work he has taken part in, on this subject.

General information only. This page does not replace individual medical advice. Updated: 10 September 2026.