Observational and Genetic Association of Myelodysplastic Syndromes (MDS) and Autoimmune Diseases in Adults

About 25% of patients with myelodysplastic syndromes (MDS) have combined autoimmune diseases (AIDs). However, the relationships between MDS and AIDs, especially a causal relationship and the underlying shared pathophysiological mechanisms, remain largely unknown. We aimed to evaluate the association between MDS and AIDs using a multicenter retrospective study, Mendelian randomization (MR), and bioinformatics analysis. About 26.6% of patients with MDS from all centers presented with AIDs. Compared to MDS patients without AIDs, MDS with AIDs was less likely to progress to acute myeloid leukemia (AML) (6.6% vs. 15.1%, p = 0.037), and the pre-existing AIDs could be used as an independent protective factor of survival (HR: 0.504, p = 0.048). Bidirectional MR results showed that MDS could cause the risk of systemic lupus erythematosus (SLE, OR: 1.09, p = 0.015), although with no significant causal relationship in other AIDs. The effect of MDS on SLE may be partially mediated by naïve CD4+ T-cells (median proportion 6.9%) and CD45RA-CD4+ T memory cells (median proportion 9.0%). Furthermore, two hub genes (IFI27 and VSIG4) were identified by machine learning and curve analysis as potential diagnostic markers for MDS with SLE. Our study suggested that the impact and mechanisms of AIDs in MDS need to be taken seriously, which could provide more accurate treatment guidance.