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To the editor, Chronic idiopathic neutropenia (CIN) of adults is a neutrophil disorder characterized by the persistent and unexplained reduction in the number of peripheral blood (PB) neutrophils below the lower limit of the normal range in a given ethnic population, for a prolonged period (more than 3 months) [1]. The diagnosis of CIN is based on exclusion criteria, namely the absence of clinical and laboratory evidence of any underlying disease that might be associated with neutropenia, absence of history of exposure to irradiation, absence of use of chemical compounds or intake of drugs that might cause neutropenia, negative antineutrophil antibody testing to exclude antibody-mediated immune neutropenia, and normal bone marrow (BM) morphology and karyotype to exclude cases of myelodysplastic syndrome (MDS) presenting as isolated neutropenia [1]. The inclusion in the diagnostic algorithm of a detailed flow cytometric analysis of the BM progenitor cells and next generation sequencing of genes related to myeloid malignancies largely contributes to the recognition of preMDS neutropenic patients [1, 2]. The etiology of CIN is not entirely known. However, there is evidence suggesting that the pathophysiology of CIN is related to an inflammatory BM microenvironment consisting of proinflammatory cytokines such as tumor necrosis factor-α, interferon-γ and interleukin-1β, proapoptotic mediators such as Fas-ligand, and activated oligoclonal or monoclonal T lymphocytes with myelosuppressive properties that collectively induce the accelerated apoptotic death of the granulocytic progenitor cells [3]. Increased levels of proinflammatory cytokines are also found in the PB of CIN patients [4]. The cellular origin of these cytokines in the BM and PB of CIN patients remains largely unknown. The possible involvement of the monocytic lineage in the pathophysiology of CIN has not been studied so far. Normally, circulating monocytes consist of phenotypically and functionally heterogeneous subpopulations, namely the classical (CD14/CD16) monocytes which represent the majority of PB monocytes displaying mainly phagocytic and tissue repair capacity, the intermediate (CD14/CD16) monocytes producing inflammatory cytokines in response to inflammatory stimuli, and the non-classical (CD14/CD16) monocytes displaying proinflammatory properties in association with patrolling and antimicrobial functions [5]. Increased number of CD16 (intermediate and non-classical) monocytes have been reported in infectious and inflammatory conditions such as cardiovascular, chronic kidney, and autoimmune diseases [5]. In the present study, we sought to evaluate by flow cytometry the quantitative characteristics of PB monocyte subsets in CIN patients (n = 70) compared to ageand sex-matched healthy individuals (n = 22). All patients fulfilled the abovedescribed diagnostic criteria of CIN and had mean neutrophil counts 1127 ± 529/μL (range 100–1700/μL) for a mean period of 144 ± 78 months (range 24–312 months). For the definition of neutropenia, we used the threshold of 1800/μL for the absolute neutrophil count according to the World Health Organization [6]. None of the patients had evidence of active infection, cardiovascular, chronic kidney, or autoimmune disease. Detailed patient characteristics are shown in the Supplemental Table 1. The study has been approved by the Ethics Committee of the University Hospital of Heraklion, and informed consent according to the Helsinki Protocol was obtained from all subjects studied. The proportion of the PBmonocyte subsets, namely the classical CD14/CD16, intermediate CD14/CD16, and non-classical CD14/ CD16 cells, was evaluated on the basis of their relative Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10875-019-00694-5) contains supplementary material, which is available to authorized users.