A Novel Strategy to Identify Haematology Patients at High Risk of Developing Aspergillosis.

Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE

Original Publication: [Lausanne : Frontiers Research Foundation]

Aspergillosis/*epidemiology ; Aspergillus fumigatus/*immunology ; Invasive Fungal Infections/*epidemiology ; Lectins, C-Type/*blood ; Leukemia, Myeloid, Acute/*complications; Adult ; Aged ; Aspergillosis/diagnosis ; Aspergillosis/immunology ; Aspergillosis/microbiology ; Aspergillus fumigatus/isolation & purification ; Biomarkers, Tumor/blood ; Biomarkers, Tumor/immunology ; Biomarkers, Tumor/metabolism ; Female ; Gene Expression Profiling ; Graft vs Host Disease/immunology ; Graft vs Host Disease/prevention & control ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/adverse effects ; Invasive Fungal Infections/diagnosis ; Invasive Fungal Infections/immunology ; Invasive Fungal Infections/microbiology ; Lectins, C-Type/immunology ; Lectins, C-Type/metabolism ; Leukemia, Myeloid, Acute/blood ; Leukemia, Myeloid, Acute/immunology ; Leukemia, Myeloid, Acute/therapy ; Male ; Middle Aged ; Polymerase Chain Reaction ; Risk Assessment/methods ; Transplantation, Homologous/adverse effects ; Young Adult

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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Griffiths, White, Thompson, da Fonseca, Pickering, Ingram, Wilson, Barnes, Taylor and Orr.)

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099953/Z/12/Z United Kingdom WT_ Wellcome Trust; 107964/Z/15/Z United Kingdom WT_ Wellcome Trust

Keywords: Aspergillus; CLR; aspergillosis; fungal immunology; host-pathogen interactions

0 (Biomarkers, Tumor)
0 (Immunosuppressive Agents)
0 (Lectins, C-Type)

Date Created: 20220103 Date Completed: 20220214 Latest Revision: 20220214

20231215

PMC8716727

10.3389/fimmu.2021.780160

34975870