Minor populations of paroxysmal nocturnal hemoglobinuria‐type cells in patients with chronic idiopathic neutropenia

Abstract

Chronic idiopathic neutropenia (CIN) is an acquired disorder of granulopoiesis characterized by increased apoptosis of the bone marrow (BM) granulocytic progenitor cells under the influence of pro-inflammatory mediators and oligoclonal/monoclonal T-lymphocytes. Because patients with immune-mediated BM failure display frequently paroxysmal nocturnal hemoglobinuria (PNH)-type cells in the peripheral blood (PB), we investigated the possible existence of PNH-type cells in 91 patients with CIN using flow cytometry. The patients displayed increased proportions of PNH-type glycophorin A /CD59 and glycophorin A /CD59 red blood cells (RBCs), FLAER /CD24 granulocytes, and FLAER /CD14 monocytes, compared to controls (n = 55). A positive correlation was found between the proportions of PNH-type RBCs, granulocytes, and monocytes and an inverse correlation between the number of PB neutrophils and the proportions of PNH-type cell populations. The number of patients, displaying percentages of PNH-type cells above the highest percentage observed in the control group, was significantly increased among patients with skewed compared to those with normal T-cell receptor repertoire suggesting that T-cell-mediated immune processes underlie the emergence of PNH-type cells in CIN. Our findings suggest that patients with CIN display PNH-type cells in the PB at a high frequency corroborating the hypothesis that CIN belongs to the immune-mediated BM failure syndromes.

An update on the diagnosis and treatment of chronic idiopathic neutropenia

“…[27] Damianaki recently reported investigations in 91 CIN patients demonstrating the presence of small numbers of PNH type clones in these patients using flow cytometry. [28] Cumulatively this work suggests that CIN is an immune-mediated bone marrow failure syndrome that impairs normal production of neutrophils in the bone marrow. [29]…”

Paroxysmal Nocturnal Hemoglobinuria in the Context of a Myeloproliferative Neoplasm: A Case Report and Review of the Literature

“…Our patient, along with the others described, allows several clinical and pathogenic considerations about the rare coexistence of PNH and MPN. Besides AA and MDS, PNH clones have been detected also in the context of lymphoid disorders, such as acute lymphoblastic leukemia and lymphomas (9,36), and in autoimmune/idiopathic cytopenias (6)(7)(8)37). The review of the literature highlighted that about 10% of MPN patients harbor a PNH clone (26,29,30), and this frequency rises up to 17% if clones smaller than 1% are considered (27).…”

“…PNH has been described in the context of bone marrow failure (BMF) syndromes, namely, aplastic anemia (AA) and myelodysplastic syndrome (MDS) (4). However, with the development of more sensitive cytofluorimetric techniques (5), PNH clones of various sizes are increasingly being detected in various onco-hematologic and autoimmune disorders (6)(7)(8)(9). The coexistence of PNH and myeloproliferative neoplasms (MPNs) has been reported, but its clinical/prognostic significance and therapeutic management are still poorly known.…”

Immune Phenomena in Myeloid Neoplasms: An “Egg or Chicken” Question

“…Consistently, anti- erythroblast antibodies have been demonstrated in about 2/3 of early MDS together with increased values of the pro-apoptotic protein Bax and decreased levels of Bcl‐2 levels, and their BM culture supernatants induced dyserythropoietic signs, erythroblastic clustering, and increased overall in cultured normal BM ( 47 , 48 ). Furthermore, small PNH clones have been demonstrated in hypomegakaryocytic thrombocytopenia ( 49 , 50 ) and chronic idiopathic neutropenia ( 51 ), two conditions hardly distinguishable from ICUS and with autoimmune reactivity against BM precursors. Finally, small PNH clones have been reported also in a considerable proportion of AIHAs, conferring a prominent hemolytic pattern and a higher thrombotic risk to the disease.…”