The correlation between genetic variants found in patients with myelodysplastic syndromes (MDS) and mechanisms underlying systemic inflammatory autoimmune diseases (SIAD) appears to be limited, according to a study published in Inflammation Research.

To investigate the presence of a molecular genetic trigger related to the development of SIAD in patients with MDS, the researchers enrolled 81 study participants with a diagnosis of MDS. They performed target-next generation sequencing, tested for antinuclear antibodies (ANA), and characterized the ANA antigenic specificity by ANA profile, extractable nuclear antigen screen, and anti-dsDNA. The study also enrolled nonhematological patients and healthy donors as controls.

“A genetic predisposition associated with a concomitant dysfunction of the innate immune system, autoimmune phenomena, and inflammation disorders may be one of the possible causes of SIAD that have been reported in 10–30% of MDS patients,” Cristiano and colleagues noted.

According to the results, patients with MDS had significantly increased levels of ANA but low ANA antigenic specificity. ANA greater than or equal to 1:160-positive patients with MDS had a comparable mutational landscape as patients with no ANA or those with ANA less than 1:160. The researchers found no significant associations between the mutational and immunological profiles and no UBA1 mutations related to vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome.

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“Although a statistically increased presence of ANA was found in our MDS cohort, the low antigenic specificity may suggest how these autoantibodies are not directed against pathognomonic antigens of autoimmune disorders, but rather against different proteins that might be associated to inflammatory cross-reactions and systemic inflammation phenomena, typically found in patients with hematologic disorders, or toward tumor-associated antigens not yet identified in the context of MDS,” the study authors explained.

The association and prognostic value of SIAD in MDS remain controversial, although many patients with MDS may develop autoimmune conditions. SIAD in patients with MDS often manifests as systemic vasculitis, connective tissue disorders, immunohematological disorders, and serological abnormalities.


Cristiano A, Belardi R, Hajrullaj H, et al. Correlation analysis between auto-immunological and mutational profiles in myelodysplastic syndromes. Inflamm Res. Published online July 28, 2023. doi:10.1007/s00011-023-01773-5