Autoimmunity and Inflammation in Myelodysplastic Syndromes

Abstract

Autoimmune and inflammatory conditions (AICs) are encountered in up to 25% of patients with myelodysplastic syndromes (MDS). A wide range of AICs have been reported in association with MDS and can range from limited clinical manifestations to systemic diseases affecting multiple organs. Vasculitides, connective tissue diseases, and inflammatory arthritis are frequently reported in different studies; noninfectious fever and constitutional symptoms at presentation are common. Associations between AICs and specific MDS characteristics vary by study, but the available data suggest that AICs cluster more often in younger patients with higher-risk MDS. In general, AICs do not seem to confer worse survival, although certain AICs may be associated with adverse outcome (e.g. vasculitis) or progression of MDS (Sweet's syndrome). Nonetheless, these complications may have a significant impact on quality of life and affect the timing and type of MDS-directed therapy. The mainstay of management of these complications in the short term relies on immunosuppressive drugs. Increasing evidence suggests that hypomethylating agents may be effective in treating these complications and reduce steroid dependence. While the pathogenesis of AICs is incompletely understood, growing appreciation of cellular immune deregulation, cytokine hypersecretion, and the genetic heterogeneity underlying MDS may improve our understanding of common pathways linking MDS, inflammation, and autoimmunity.

Pro-inflammatory cytokine blockade attenuates myeloid expansion in a murine model of rheumatoid arthritis

“…Such a model is in line with an emerging body of work showing that proinflammatory signaling can play a positive role in hematopoiesis8 . This model could explain the rarity of bone marrow failure in RA patients despite some increased risk of myelodysplastic syndrome (MDS)41 , as well as the rarity of graft failure for RA patients undergoing autologous BM transplant42 .While concurrent activation of myeloid differentiation and proliferation arrest gene programs in HSC seems paradoxical, cell cycle arrest is crucial for myeloid differentiation by promoting accumulation of factors needed for differentiation43 . Myeloid transcription factors including PU.1 promote cell cycle arrest via induction of cell cycle inhibitors like Cdkn1a while repressing cell cycle activators like Ccnd1 43,44 .…”

Association of Myelodysplastic Syndrome and Autoimmune Disorders in North Kerala

“…11,8 Overall survival was more in patients with autoimmune disorders and transformation to AML was low in these patients. 12,13 It was noted by Mekinian A, Grignano E et al from a French multicentric study published in 2016 that one third of patients had their autoimmune disorder diagnosed at the same time as their diagnosis of myelodysplastic syndrome and a third each before and after the diagnosis of myelodysplastic syndrome. 14 The average duration in this study from the diagnosis of myelodysplastic syndrome to the appearance of autoimmunity was 8.4 months.…”

“…These autoimmune phenomenon occurring does not seem to confer worse survival although vasculitis has been shown to have a bad prognosis. 13,14 As the study was done during the period of 2009 to 2013, the differentiation between the condition of CCUS (clonal cytopenias of undetermined significance)and MDS was not fully characterized. The relatively high incidence of autoimmunity in the present study may be due to the inclusion of autoimmune diseases manifesting as CCUS being included as undifferentiated MDS.…”

Myelodysplastic Syndromes: An Update on Pathophysiology and Management

“…Lymphadenopathy and hepatosplenomegaly are infrequent and should raise suspicion for chronic myelomonocytic leukemia (CMML) [13,14]. It has been estimated that various autoimmune features such as subacute vasculitis, fever, arthritis, peripheral edema, and pulmonary infiltrates, may be present in up to 10% of patients [15][16][17][18]. Certain autoimmune syndromes have correlated with distinct cytogenetic abnormalities; including Behcet's disease with trisomy 8, Sweet's syndrome and pyoderma gangrenosum with del(5q) [19].…”