M Mansour Ceesay1, Shahram Kordasti2, Eamaan Rufaie2, Nicholas Lea2, Melvyn Smith3, Jim Wade4, Abdel Douiri5, Ghulam J Mufti2, Antonio Pagliuca2. 1. Department of Haematological Medicine, King's College Hospital NHS Foundation Trust and King's College London, London, SE5 9RS, United Kingdom. Electronic address: mansour.ceesay@nhs.net. 2. Department of Haematological Medicine, King's College Hospital NHS Foundation Trust and King's College London, London, SE5 9RS, United Kingdom. 3. Department of Virology, King's College Hospital NHS Foundation Trust, SE5 9RS, United Kingdom. 4. Department of Microbiology, King's College Hospital NHS Foundation Trust, London, SE5 9RS, United Kingdom. 5. Department of Public Health Science, King's College London and NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, United Kingdom.
Abstract
BACKGROUND: Invasive fungal disease (IFD) is a disease of immunocompromised hosts. Cytokines are important mediators of innate and adaptive immune system. The aim of this study was to identify cytokine profiles that correlate with increased risk of IFD. METHODS: We prospectively enrolled 172 adult haematology patients undergoing intensive chemotherapy, immunosuppressive therapy, and haematopoietic stem cell transplantation. Pro-inflammatory cytokine profiling using 30-plex Luminex assay was performed at baseline and during treatment. Nine single nucleotide polymorphisms (TLR1, TLR2, TLR3, TLR4.1, TLR4.2, TLR6, CLEC7A, CARD9, and INFG) were investigated among transplant recipients and donors. FINDINGS: The incidence of IFD in this cohort was 16.9% (29/172). Median baseline serum concentrations of IL-15, IL-2R, CCL2, and MIP-1α were significantly higher whilst IL-4 was lower in patients with proven/probable IFD compared to those with no evidence of IFD. Baseline high IL-2R and CCL2 were associated with increased risk of IFD in the multivariate analysis (adjusted hazard ratio 2.3 [95% CI 1.1-5.1; P = 0.037], and hazard ratio 2.7 [95% CI 1.2-6.1; P = 0.016], respectively). However, these differences were not significant in follow up measurements. Similarly, no significant independent prognostic value was associated with baseline cytokine profile. INTERPRETATION: High baseline IL-2R and CCL2 concentrations were independent indicators of the risk of developing IFD and could be used to identify patients for enhanced prophylaxis and early antifungal therapy. Crown
BACKGROUND:Invasive fungal disease (IFD) is a disease of immunocompromised hosts. Cytokines are important mediators of innate and adaptive immune system. The aim of this study was to identify cytokine profiles that correlate with increased risk of IFD. METHODS: We prospectively enrolled 172 adult haematology patients undergoing intensive chemotherapy, immunosuppressive therapy, and haematopoietic stem cell transplantation. Pro-inflammatory cytokine profiling using 30-plex Luminex assay was performed at baseline and during treatment. Nine single nucleotide polymorphisms (TLR1, TLR2, TLR3, TLR4.1, TLR4.2, TLR6, CLEC7A, CARD9, and INFG) were investigated among transplant recipients and donors. FINDINGS: The incidence of IFD in this cohort was 16.9% (29/172). Median baseline serum concentrations of IL-15, IL-2R, CCL2, and MIP-1α were significantly higher whilst IL-4 was lower in patients with proven/probable IFD compared to those with no evidence of IFD. Baseline high IL-2R and CCL2 were associated with increased risk of IFD in the multivariate analysis (adjusted hazard ratio 2.3 [95% CI 1.1-5.1; P = 0.037], and hazard ratio 2.7 [95% CI 1.2-6.1; P = 0.016], respectively). However, these differences were not significant in follow up measurements. Similarly, no significant independent prognostic value was associated with baseline cytokine profile. INTERPRETATION: High baseline IL-2R and CCL2 concentrations were independent indicators of the risk of developing IFD and could be used to identify patients for enhanced prophylaxis and early antifungal therapy. Crown
Authors: Samuel M Gonçalves; Katrien Lagrou; Cláudia S Rodrigues; Cláudia F Campos; Leticia Bernal-Martínez; Fernando Rodrigues; Ricardo Silvestre; Laura Alcazar-Fuoli; Johan A Maertens; Cristina Cunha; Agostinho Carvalho Journal: Front Microbiol Date: 2017-11-29 Impact factor: 5.640
Authors: Harini D de Silva; Rosemary A Ffrench; Maya Korem; Eva Orlowski; David J Curtis; Andrew Spencer; Sharon Avery; Sushrut Patil; Catherine Orla Morrissey Journal: Clin Transl Immunology Date: 2018-10-05