New insights into chronic idiopathic neutropenia

Chronic idiopathic neutropenia (CIN) is a relatively common disorder predominantly affecting women. Blood neutrophil counts are less than 1.5 × 10⁹/L, but other blood cell counts are normal. Bone marrow examination, if performed, usually shows only a modest reduction in metamyelocytes and neutrophils. In general, the severity of the neutropenia does not worsen, and patients do not evolve to develop systemic lupus erythematosus, aplastic anemia, or leukemia. If blood neutrophil counts are less than 0.5 × 10⁹/L, fever and minor infections are common, and treatment with recombinant G-CSF can be helpful.

In this issue Papadaki and colleagues (page 2591) provide valuable new insights suggesting that the mechanism for neutropenia in CIN is similar to that in Felty syndrome, that is, accelerated apoptosis of neutrophil precursors due to excessive production of interferon gamma and tumor necrosis by immune cells in the bone marrow. In their study of 28 women and 4 men, they observed that the percentages of marrow CD34⁺ and CD34⁺/CD33⁺ cells were reduced and a higher than normal percentage of the CD34⁺ cells were apoptotic. Separated CD34⁺ cells had reduced colony-forming capacity and grew less well in long-term cultures than similar normal cells. Supernates from these long-term cultures contained increased amounts of proinflammatory cytokines known to inhibit myelopoiesis.

This paper from Crete is remarkable for the thoroughness of the investigations, the long-term follow-up of the patients, and the new insights it provides about a heretofore poorly understood entity. It helps us connect idiopathic neutropenia to the autoimmune disorders, that is, lupus erythematosus and rheumatoid arthritis, by finding a similar mechanism for neutropenia. It also adds another condition to the growing list of diseases for which accelerated apoptosis of progenitor cells is the underlying cellular mechanism of neutropenia.