Beyond HNA-1: The anti-HNA-3 autoantibody as a protagonist in autoimmune neutropenia

Autoimmune neutropenia (AIN), a common cause of chronic neutropenia, has been categorized as primary (pAIN) and secondary (sAIN). This study investigates the specificity of anti-HNA autoantibodies in both types.

A prospective cohort study of 85 chronic neutropenia patients included those with detectable anti-HNA autoantibodies. Anti-HNA was assessed using granulocyte agglutination (GAT), granulocyte immunofluorescence (GIFT), and LABScreen Multi Kit (LSM). Molecular analysis was performed to assess HNA expression.

Of 85 patients, 7 had pAIN and 8 had sAIN. All pAIN patients exhibited only anti-HNA-1, while anti-HNA-3 was found in 3/8 sAIN patients. All patients with anti-HNA-3 tested positive in LSM; one was positive in both GAT and GIFT.

While anti-HNA-3 has been described exclusively as an alloantibody, this is the first report of anti-HNA-3 as an autoantibody in AIN.

Anti-HNA-3 autoantibody is associated only with sAIN, suggesting distinct mechanisms in pAIN and sAIN.