A novel strategy to identify haematology patients at high risk of developing Aspergillosis

Griffiths, James S., White, P. Lewis, Thompson, Aiysha, Matos Da Fonseca, Diogo M., Pickering, Robert J., Ingram, Wendy, Wilson, Keith, Barnes, Rosemary, Taylor, Philip R. ORCID: https://orcid.org/0000-0003-0163-1421 and Orr, Selinda J. 2021. A novel strategy to identify haematology patients at high risk of developing Aspergillosis. Frontiers in Immunology 12 , 780160. 10.3389/fimmu.2021.780160

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Abstract

Invasive Aspergillosis (IA), typically caused by the fungus Aspergillus fumigatus, is a leading cause of morbidity and mortality in immunocompromised patients. IA remains a significant burden in haematology patients, despite improvements in the diagnosis and treatment of Aspergillus infection. Diagnosing IA is challenging, requiring multiple factors to classify patients into possible, probable and proven IA cohorts. Given the low incidence of IA, using negative results as exclusion criteria is optimal. However, frequent false positives and severe IA mortality rates in haematology patients have led to the empirical use of toxic, drug-interactive and often ineffective anti-fungal therapeutics. Improvements in IA diagnosis are needed to reduce unnecessary anti-fungal therapy. Early IA diagnosis is vital for positive patient outcomes; therefore, a pre-emptive approach is required. In this study, we examined the sequence and expression of four C-type Lectin-like receptors (Dectin-1, Dectin-2, Mincle, Mcl) from 42 haematology patients and investigated each patient’s anti-Aspergillus immune response (IL-6, TNF). Correlation analysis revealed novel IA disease risk factors which we used to develop a pre-emptive patient stratification protocol to identify haematopoietic stem cell transplant patients at high and low risk of developing IA. This stratification protocol has the potential to enhance the identification of high-risk patients whilst reducing unnecessary treatment, minimizing the development of anti-fungal resistance, and prioritising primary disease treatment for low-risk patients.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)
Publisher:	Frontiers Media
ISSN:	1664-3224
Date of First Compliant Deposit:	17 February 2022
Date of Acceptance:	1 December 2021
Last Modified:	11 Oct 2023 22:17
URI:	https://orca.cardiff.ac.uk/id/eprint/147619

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