Objective and design: Systemic-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 materials: Eighty-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.
Results: At clinically relevant cut-off (≥ 1:160), ANA was significantly more frequent in MDS, while ANA-antigenic-specificity showed a low association rate. ANA ≥ 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.
Conclusions: Although 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.
Keywords: ANA antigenic specificity; Anti-nuclear antibodies (ANA); Auto-immunological profile; Inflammatory and autoimmune diseases; Mutational profile; Myelodysplastic syndromes; VEXAS.
© 2023. The Author(s).