Primary autoimmune neutropenia (pAN) is typified by onset in early infancy and a mild/ moderate phenotype that resolves within 3 years of diagnosis. In contrast, secondary AN is classically an adult disease associated with malignancy, autoimmunity, immunodeficiency, viral infection, or drugs. This study describes a cohort of 79 children from the Italian Registry who, although resembling pAN, did not fully match the criteria for pAN because neutropenia either appeared after age 5 years (LO-Np) or lasted longer than 3 years (LL-Np). These 2 categories compared with classical pAN showed a far inferior rate of resolution (P,.001), lower severity of neutropenia (P 5.03), leukopenia (P,.001), lymphopenia (P,.001) with low B1 (P 5.001), increased need of granulocyte colony-stimulating factor (P 5.04), and increased frequency of autoimmunity over the disease course (P,.001). A paired comparison between LO-Np and LL-Np suggested that LO-Np had a lower rate of resolution (P,.001) and lower white blood cell (P,.001) and lymphocyte (P,.001) values, higher occurrence of apthae (P 5.008), and a stronger association with autoimmune diseases/ markers (P 5.001) than LL-Np, thus suggesting a more pronounced autoimmune signature for LO-Np. A next-generation sequencing panel applied in a small subgroup of LO-Np and LL-Np patients identified variants related to immune dysregulations. Overall, these findings indicate that there are important differences among pAN LL-Np and LO-Np. Forms rising after 3 years of age, with low tendency to resolution, require tight monitoring and extensive immune investigations aimed to early identify underlying immunologic disease.
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