Correlation analysis between auto-immunological and mutational profiles in myelodysplastic syndromes

Objective and designSystemic-Inflammatory-Autoimmune-Diseases (SIAD) is increasingly considered in Myelodysplastic-Syndromes (MDS). In this line, we evaluated the MDS auto-immunological profile, correlating it to the mutational landscape, trying to identify a molecular-genetic trigger agent related to SIAD.Methods and materialsEighty-one MDS were enrolled and t-NGS was performed. Anti-Nuclear-Antibodies (ANA) were tested, and ANA-antigenic-specificity was characterized by ANA-profile, ENA-screen, anti-dsDNA. Non-Hematological-Patients (NHP) and Healthy-Donors (HD) were used as controls.ResultsAt clinically relevant cut-off (& GE; 1:160), ANA was significantly more frequent in MDS, while ANA-antigenic-specificity showed a low association rate. ANA & GE; 1:160-positive MDS showed a mutational landscape similar to ANA-negative/ANA < 1:160 MDS. No significant correlations between mutational and immunological profiles were found and UBA1 mutations, related to VEXAS, were absent.ConclusionsAlthough ANA-positivity was found to be increased in MDS, the low ANA-antigenic-specificity suggests that autoantibodies didn't recognize autoimmune-pathognomonic antigens. The lack of relationship between genetic profile and ANA-positivity, suggests that MDS genetic variants may not be the direct cause of SIAD.

Automated summary

This study evaluated the autoimmune profile of Myelodysplastic Syndromes (MDS) and correlated it with the mutational landscape, aiming to identify a molecular-genetic trigger agent related to Systemic Inflammatory Autoimmune Diseases (SIAD).