Avaliação dos mediadores inflamatórios e microbioma no exsudato de feridas de pacientes com úlcera falciforme

Abstract

Introduction: Leg ulcers in sickle cell disease (SCDLU) represent debilitating and chronic manifestations associated with disease severity, resulting in delayed wound healing and unpredictable recurrence linked to aberrant regulation of inflammatory mediators. Although elevated levels of cytokines and altered microbiome composition have been associated with impaired healing in other wound types, their specific role in SCDLU remains incompletely understood. Objective: To characterize the exudate profile of SCDLU, with particular emphasis on inflammatory mediator analysis and identification of lesion associated microbiome. Methods: Wound exudate samples were collected between January 2023 and June 2024 at the outpatient clinics of Professor Edgard Santos University Hospital (HUPES) and the State Reference Center for Sickle Cell Disease (CERPDF-RV/Hemoba) (CAAE: 56643222.0.0000.5662). This cross-sectional study analyzed clinical data, inflammatory profiles, and wound microbiome composition. Cytokines were quantified using sandwich ELISA (R&D Systems; Invitrogen), and statistical analyses were performed using GraphPad Prism (version 9). Results: The study included 40 SCD patients, comprising 63 analyzed ulcers. Median age was 41 years, with 55.0% male participants. Each patient was presented with 1-4 cutaneous lesions and laboratory data revealed chronic hemolysis and anemia. IL-6, PSGL-1, and P-selectin levels were significantly lower in ulcers with small diameter, while IFN-γ and IL-8 showed no significant differences between groups. ROC analysis indicated that IL-6, PSGL-1, and P-selectin effectively discriminated against lesion size, suggesting their potential as inflammatory biomarkers. Furthermore, larger ulcers exhibited greater bacterial diversity in microbiome analysis. Conclusion: Our findings demonstrate that IL-6, PSGL-1, and P-selectin play significant roles in SCDLU pathophysiology and may serve as reliable biomarkers for lesion size. The observed increase in bacterial diversity in extensive ulcers suggests potential microbiome involvement in perpetuating local inflammation. These results may contribute to improved clinical assessment and therapeutic management of SCD-associated ulcers.