Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Specific blood monocyte distribution in histiocytoses correlates with vascular involvement and disease activity.

Abstract

Histiocytoses are rare hematological disorders characterized by the proliferation and accumulation of CD68+ histiocytes in tissues.1 Previously considered as inflammatory conditions, several adult’s histiocytoses (Erdheim-Chester disease [ECD], Langerhans cell histiocytosis [LCH], Rosai-Dorfman disease [RDD]) are now classified as myeloid neoplasms.2 Indeed, these patients display recurrent molecular features like somatic mutations in the mitogen activating-kinase (MAP-kinase) pathway genes,1 myeloid neoplasms (chronic myelomonocytic leukemia [CMML] and essential thrombocytopenia [ET])3 or clonal hematopoiesis (CH),4 which gave rise to this paradigm shift. Despite these significant advances, the cellular origin of histiocytes is still unknown. Nevertheless, monocytes are essential to the ontogeny of histiocytic disorders.5 Circulating monocytes are divided into three subsets (“classical”, “intermediate” and “non-classical”) with a distribution influenced by the innate immune system and environmental signals.6 During histiocytoses, circulating monocytes arising from bone marrow progenitors carry most MAP-kinase gene mutations, but only “classical” monocytes can differentiate into tissue histiocytes.5 Increase in “classical” monocytes was reported in CMML7 and inflammatory states,8 while a decrease in the “nonclassical” subset was described in vascular disorders.9 However, little is known about the distribution of the circulating monocyte subsets in histiocytoses10 and their differences from other myeloid neoplasms. We, therefore, sought to evaluate the distribution of the circulating monocyte subsets in patients with histiocytoses compared to patients with myeloid neoplasms(CMML and ET) and healthy donors (HD).