RESUMEN
Preoperative glucocorticoid administration reduces the systemic inflammatory response. Pentraxin 3 (PTX3) is a novel inflammatory marker belonging to the humoral arm of innate immunity exerting a potentially protective host response. This study evaluated PTX3 and other complement marker changes after preoperative methylprednisolone (MP) early after total knee arthroplasty (TKA). Seventy patients were randomized (1 : 1) to preoperative intravenous (i.v.) MP 125 mg (group MP) or isotonic saline i.v. (group C). The outcomes included change in plasma PTX3, mannose-binding lectin (MBL), ficolins (ficolin-1, -2 and -3), complement components (C4 and C3), terminal complement complex (TCC) and C-reactive protein (CRP) concentrations. Blood samples were analysed at baseline and 2, 6, 24 and 48 h after surgery with complete sampling from 63 patients for analyses. MP resulted in an increase in circulating PTX3 compared to saline from baseline to 24 h postoperatively (P < 0·001), while MP reduced the systemic inflammatory response (CRP) 24 and 48 h postoperatively (P < 0·001). However, the small postoperative changes in MBL, ficolin-1, -2 and -3, C4, C3 and TCC concentrations did not differ between groups (P > 0·05). In conclusion, preoperative MP 125 mg increased circulating PTX3 and reduced the general inflammatory response (CRP) early after TKA, but did not affect other complement markers.
Asunto(s)
Antiinflamatorios/uso terapéutico , Artroplastia de Reemplazo de Rodilla , Biomarcadores/metabolismo , Proteína C-Reactiva/metabolismo , Inflamación/inmunología , Metilprednisolona/uso terapéutico , Componente Amiloide P Sérico/metabolismo , Anciano , Proteínas del Sistema Complemento/metabolismo , Método Doble Ciego , Femenino , Humanos , Inmunidad Innata , Lectinas/metabolismo , Masculino , Lectina de Unión a Manosa/sangre , Persona de Mediana Edad , Efecto Placebo , Cuidados Preoperatorios , FicolinasRESUMEN
Essentials Abdominal aortic aneurysm (AAA) is asymptomatic and its evolution unpredictable. To find novel potential biomarkers of AAA, microvesicles are an excellent source of biomarkers. Ficolin-3 is increased in microvesicles obtained from activated platelets and AAA tissue. Increased ficolin-3 plasma levels are associated with AAA presence and progression. SUMMARY: Background Abdominal aortic aneurysm (AAA) patients are usually asymptomatic and AAA evolution is unpredictable. Ficolin-3, mainly synthesized by the liver, is a molecule of the lectin complement-activation pathway involved in AAA pathophysiology. Objectives To define extra-hepatic sources of ficolin-3 in AAA and investigate the role of ficolin-3 as a biomarker of the presence and progression of AAA. Methods Microvesicles (exosomes and microparticles) were isolated from culture-conditioned medium of ADP-activated platelets, as well as from AAA tissue-conditioned medium (thrombus and wall). Ficolin-3 levels were analyzed by western-blot, real-time PCR, immunohistochemistry and ELISA. Results Increased ficolin-3 levels were observed in microvesicles isolated from activated platelets. Similarly, microvesicles released from AAA tissue display increased ficolin-3 levels as compared with those from healthy tissue. Moreover, ficolin-3 mRNA levels in the AAA wall were greatly increased compared with healthy aortic walls. Immunohistochemistry of AAA tissue demonstrated increased ficolin-3, whereas little staining was present in healthy walls. Finally, increased ficolin-3 levels were observed in AAA patients' plasma (n = 478) compared with control plasma (n = 176), which persisted after adjustment for risk factors (adjusted odds ratio [OR], 5.29; 95% confidence interval [CI], 3.27, 8.57)]. Moreover, a positive association of ficolin-3 with aortic diameter (Rho, 0.25) and need for surgical repair was observed, also after adjustment for potential confounding factors (adjusted hazard ratio, 1.55; 95% CI, 1.11, 2.15). Conclusions In addition to its hepatic expression, ficolin-3 may be released into the extracellular medium via microvesicles, by both activated cells and pathological AAA tissue. Ficolin-3 plasma levels are associated with the presence and progression of AAA, suggesting its potential role as a biomarker of AAA.