Autoimmune manifestations associated with myelodysplastic syndromes

Abstract

Autoimmune disorders (ADs) are encountered in 10 to 20% of patients with myelodysplastic syndromes (MDS). Available data suggest that ADs concern more often younger patients with higher risk IPSS. MDS subtypes associated with ADs are mainly MDS with single lineage dysplasia (MDS-SLD) and MDS with excess blasts (MDS-EB). Various types of ADs have been described in association with MDS, ranging from limited clinical manifestations to systemic diseases affecting multiple organs. Defined clinical entities as vasculitis, connective tissue diseases, inflammatory arthritis, and neutrophilic diseases are frequently reported; however, unclassified or isolated organ impairment can be seen. In general, ADs do not seem to confer worse survival, although certain ADs may be associated with adverse outcomes (i.e., vasculitis) or progression of MDS (Sweet syndrome). While steroids and immunosuppressive treatment (IST) remain the backbone of first-line treatment, increasing evidence suggests that MDS-specific therapy as hypomethylating agents, based on their immunomodulatory effect, may be effective in treating these complications and for sparing steroids.

Myelodysplastic syndrome-associated spliceosome gene mutations enhance innate immune signaling

“…15 In particular, IL-6 influences HSC development and has paracrine function in HSPC, leading to overproduction of myeloid cells and aberrant hematologic features found in MDS patients. [16][17][18] Second, our results raise the possibility that altered innate immune signaling induced by spliceosome mutations could alter immune cell function, contributing to the increased risk of infection and/or hyperinflammatory features common to MDS patients, 19,20 a possibility that we will explore in future studies. Finally, while we focus on the role of spliceosome mutations in MDS, spliceosome mutations are present in many hematologic malignancies 1 and could affect pathogenesis of other cancers using similar mechanisms.…”

Spectrum of Kidney Involvement in Patients with Myelodysplastic Syndromes

“…Some of these nephropathies have been previously reported in MDS patients in a limited number of case reports, particularly membranous nephropathy (Table 4). However our findings are remarkable for the presence of very rare glomerulopathies: ANCA-negative pauci-immune necrotizing and crescentic glomerulonephritis 18 , crescentic C3 glomerulopathy 19 , fibrillary glomerulonephritis 20 However, the exact mechanisms underlying autoimmune manifestations in MDS patients remain speculative 24 .…”

“…Furthermore, as already stated, autoimmunity is a wellrecognized feature of MDS in extra-renal organs. Half of the patients included in this series had extra-renal manifestations at the time of kidney biopsy and 20% had autoantibodies, even though the latter are not necessarily pathogenic 24…”

The Genomics of Myelodysplastic Syndromes: Origins of Disease Evolution, Biological Pathways, and Prognostic Implications

“…Bone marrow biopsy is usually supportive in making a definitive diagnosis of MDS. Notably, 10-20% of patients with MDS have a clinical presentation with autoimmune manifestation such as inflammatory arthritis, vasculitis, and connective tissue diseases [144]. Immune dysregulation has been implicated in the pathogenesis of autoimmune disease, and these patients respond to immune-suppressive agents such as corticosteroids [145,146].…”