Circulating monocytes decrease significantly following disease-directed therapy and may reflect disease expansion in Langerhans Cell Histiocytosis

Author:

Ali Haadi1,Reynolds Sam1,Wilcox Sabrina1,Chipalkatti Naina1,Ahmed Asra1

Affiliation:

1. Michigan Medicine

Abstract

Abstract

We aimed to examine the association between relative monocytosis and the recurrence of pulmonary Langerhans Cell Histiocytosis. Clinical, laboratory, radiographic and treatment data for 86 patients with a histopathological diagnosis of Langerhans Cell Histiocytosis over a 20-year duration. Parameters such as biological sex, age at diagnosis, time to diagnosis, molecular diagnostic data and imaging were collected. Treatment responses were assessed predominantly through radiography, with RECIST 1.1 criteria applied to MRI or CT scans and PERCIST utilized for serial PET imaging. Investigators also assessed peripheral blood absolute monocyte count at various time points, including initial diagnosis and the most recently available value. While peripheral blood absolute monocyte count between the earliest assessed timepoint and latest value did not differ, the mean value on progression (0.94 K/µL), however, was significantly higher than that following re-institution of therapy (0.31, p = 0.000794. Our observation of relative monocytosis on LCH disease progression may be related to an increase in circulating LCH on disease progression or from increased monocyte production for later differentiation into mature dendritic cells that participate in MHC Class 1 upregulation. This trend is especially evident in pulmonary LCH which is incited by tissue trauma and irritation by environmental factors. The phenomena observed in our study parallel other non-LCH cohorts, specifically in published findings from our own group in patients with Rosai Dorfman and Erdheim Chester Disease. To further elucidate the molecular underpinnings of LCH and explore the etiology of this monocyte trend, expanded integrated genomic-transcriptomic sequencing analyses to evaluate the molecular character of LCH and ultimately clarify the origin of this monocyte trend are in progress. These studies are poised to offer invaluable insight to the molecular mechanisms underlying LCH, specifically as they pertain to monocyte signaling and differentiation.

Publisher

Springer Science and Business Media LLC

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