High level of admission H3.1 nucleosome is associated with invasive fungal infections in severely burn patients

Position du problème et objectif(s) de l’étude

NETosis is a key innate immune defence mechanism in which neutrophils release DNA to form extracellular traps (NETs). NETosis is implicated in antifungal immunity. We investigated the association between invasive fungal infection (IFI) and H3.1 nucleosome level, organ failure and outcome including mortality at D-90 in severely burn patients.

Matériel et méthodes

We analyzed levels of H3.1 nucleosome at admission and D-3 in 84 patients with severe burn injury admitted in a French teaching hospital. We evaluated associations between occurrence of probable invasive fungal infection (define by EORTC criteria for invasive candidiasis and define by ≥ 2 positive cultures from skin biopsies/Bronchoalveolar lavage OR ≥ 2 positive blood specific q-PCR OR combination of both for invasive mold infection) and H3.1 nucleosome levels, organ failure defined by TBSA (Total Burn Surface Area), use of catecholamines in the first two days, Acute Respiratory Distress Syndrome (ARDS), Acute Kidney injury (AKI) and septic shock using multivariable Cox regression and receiver operating characteristic (ROC) analyses.

Résultats & Discussion

Thirty-one (40%) patients developed an invasive fungal infection including 15 (18%) invasive candidiasis with candidemia and 20 (24%) probable mold infections. In univariate analysis, invasive fungal infection was associated with age (years) (42 [32-54] vs 52 [41-65]), TBSA (%) (24[19-35] vs 43[30-70]), volume of fluid in the first 24 hours (liter) (9245 [5120-13288] vs 14 550 [11 500-21 000]), occurrence of ARDS (13 (25%) vs 21 (68%)) and of septic shock (13 (25%) vs 30 (97%)) (p <0.05). Mortality at D-90 did not differ between IFI and non-IFI (5 (16.1%) vs 5 (9.4%), p=0.487). Multivariate Cox regression identified age OR 1.05 CI [1.01-1.09], p=0.025, number of surgeries 1.46 [1.20-1.88], p=0.001 and high level of admission H3.1 nucleosome 5.45 [1.21-28.18], p=0.032 as independent variables associated with invasive fungal infections. The area under the curve of the admission H3.1 nucleosome for predicting invasive fungal infections in burn patients was 0.75 (95% CI 0.64-0.86) and was no better than ABSI for which the prediction was 0.80 (0.70-0.89). The cut-off value of nucleosome H3.1 was 389 ng/mL (specificity =89% and sensibility=40% ).

Conclusion

Age, number of surgeries and elevated H3.1 nucleosome level on admission are independently associated with invasive fungal infections. An excess of NETose in the immediate post-burn period would lead to a reduction in NETose capacity as the neutrophil pool replenishes and could increase the patient's susceptibility to fungal infections. This data demonstrate for the first time the link between NETosis and the occurrence of invasive fungal infections in severely burn patients.

Auteurs

Emmanuel DUDOIGNON (1) , Fidaa IBRAHIM (2), Sarah DELLIÈRE (3), Christian DE TYMOWSKI (4), François DÉPRET (1) - (1)Hopital Saint Louis-Université Paris Cité, Paris, France, (2)Hopital Saint Louis, Paris, France, (3)Institut Pasteur-Université Paris Cité-Hôpital Saint Louis, Paris, France, (4)Hopital Bichat-Louis Mourier-Université Paris Cité, Paris, France

Orateur(s)

Emmanuel DUDOIGNON (Paris)