Longitudinal characterization of olfactomedin-4 expressing neutrophils in pediatric patients undergoing bone marrow transplantation.

Julie E Stark,Matthew N Alder,Amy M Opoka,Huaiyu Zang,Hector R Wong,Lin Fei,Stella M Davies,Sakamuri V Reddy

doi:10.1371/journal.pone.0233738

Julie E Stark, Matthew N Alder + Show 6 more

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https://doi.org/10.1371/journal.pone.0233738

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Abstract

Sepsis is an important cause of morbidity and mortality in pediatric patients. Increased expression of olfactomedin-4 (OLFM4), a glycoprotein contained within a subpopulation of neutrophils, has been associated with complicated course in sepsis. The factors that regulate OLFM4 expression are unknown. Here, we followed children undergoing bone marrow transplantation (BMT) to document the percentage of neutrophils that express OLFM4 over time. This population was selected because of the ability to observe nascent neutrophils following engraftment, perform frequent blood sampling, and the children are at high risk for clinical complications that may associate with changes in percentage of OLFM4+ neutrophils. We found a surprising degree of variability of OLFM4 expression between patients. In the weeks following initial neutrophil recovery we also saw great variability in OLFM4 expression within individual patients, indicating that multiple external factors may modify OLFM4 expression. We identified decreased expression of CD64 (a marker associated with response to infection), in OLFM4+ neutrophils. This is the first study to demonstrate fluctuation in OLFM4 expression within patients and provides insight into possible mechanisms for OLFM4 regulation in nascent neutrophils.

Highlights

Neutrophils are the most abundant white blood cell in peripheral blood and are the primary mobile arm of the innate immune system
To evaluate if host factors were responsible for determining percentage of OLFM4+ neutrophils, we assessed for correlation between percentage of OLFM4+ neutrophils before and after Bone marrow transplantation (BMT) for each patient using their last percentage prior to myeloablative therapy and their first measurement after 14 days and found no correlation (p = 0.11; Fig 1B)
To test if there was a general trend of increase or decrease in percentage of OLFM4+ neutrophils following engraftment over time we evaluated all samples by week post-BMT and no significant difference was seen in percentage of OLFM4+ neutrophils on any given week (Fig 1C)

Summary

Introduction

Neutrophils are the most abundant white blood cell in peripheral blood and are the primary mobile arm of the innate immune system. Thought of as primarily phagocytes, there is more appreciation for the roles of neutrophils in adaptive immune responses and healing [1, 2]. Patients who are neutropenic due to primary disease or therapy have increased susceptibility to infections, especially bacterial. Bone marrow transplantation (BMT) is a life-saving procedure for many children with genetic and hematologic diseases, but complete ablation of host marrow and replacement with HLA matched donor stem cells requires intensive. Olfactomedin-4 expressing neutrophils in pediatric patients undergoing bone marrow transplantation

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