604. IL-17C as an early diagnostic biomarker for invasive fungal infection or just a marker of any infection in at-risk haematology patients
Authors: Aerts Robina , Ponce Isis Ricano , Bruno Mariolina , Mercier Toine , Rosati Diletta , Maertens Johan A , Kumar Vinod , Carvalho Agostinho , Netea Mihai , Hoenigl Martin 
Published: November 2023

Abstract

Background
As mortality of invasive mould infections (IMI) remains high, there is a need for improved biomarkers for timely diagnosis and patient stratification. Various moulds have been shown to induce T-helper cell (Th) 1, Th2, Th9 and Th17 subsets resulting not in potent anti-Aspergillus T-cells effector mechanisms, and in elevated serum levels of cytokines such as IFN-γ and IL-6, IL-8, IL-15 and IL-17. The ECMM study “Immunologic Markers for Treatment Monitoring and Diagnosis in Invasive Mold Infection” aimed to identify circulating immunological markers that could be useful for an early diagnosis of IMI.

Methods
We collected longitudinal serum samples from 33 cases with probable/proven IMI and two matched control cohorts without IMI, and from an independent validation cohort with 20 cases and 20 matched controls (Figure 1, Table 1). None of the patients received mold active prophylaxis. A panel of 92 circulating proteins involved in inflammation was measured using a targeted proteomics platform (Olink Proteomics AB (Uppsala, Sweden)) and protein concentrations were compared. Correction for multiple testing was performed by Benjamini-Hochberg method.
Figure 1
Overview of sample collection
Table 1
An overview of the main characteristics of and differences between the derivation cohort and the validation cohort, including characteristics of all cases and all controls.

Results
Abundance analysis on the day of diagnosis revealed 30 differentially regulated proteins. Nine were replicated in an independent cohort: MMP-10, IL-18, IL-18-R1, IL10, CDCP1 and IL-17C. In the analysis of serum samples collected more than 10 days before diagnosis, six proteins showed higher concentrations in the cases compared to the controls (CCL20, IL-6, IL-17C, CCL23, CXCL5, CXCL1 and CX3CL1), while nine proteins had lower concentrations (Figure 2). The higher IL-17C concentration could be replicated in the independent validation cohort (Figure 3). When comparing cases only to infected controls this difference in expression was not significant anymore after correcting for multiple testing.
Figure 2
Figure 3

Conclusion
We found a consistent higher expression of IL-17C in cases with IMI versus non-infected controls, both at the time of diagnosis and in samples 10 days before the diagnosis of IMI. IL-17C, known for its pro-inflammatory function at the epithelial sites, activates expression of other proinflammatory cytokines and of chemokines such as CXCL1/2/3 and CCL20, and could present an early biomarker for IMI.
Abundance analysis of the primary cohort (a) at time of diagnosis, and (b) at more than 10 days before diagnosis, comparing cases with non infected controls.
Abundance analysis of the validation cohort (a) at time of diagnosis, and (b) at more than 10 days before diagnosis, comparing cases with non infected controls.
Table 2-1
Table 2
Clinical and microbiological information of the 33 cases included in the primary cohort and the 20 cases included in the validation cohort PART 1.

Disclosures
Martin Hoenigl, n/a, Astellas: Grant/Research Support|Euroimmun: Grant/Research Support|F2G: Grant/Research Support|Gilead: Grant/Research Support|Immy: Grant/Research Support|MSD: Grant/Research Support|Mundipharma: Grant/Research Support|Pfizer: Grant/Research Support|Pulmocide: Grant/Research Support|Scynexis: Grant/Research Support