Granulomatosis con poliangeitis (de Wegener) asociada a dengue / Granulomatosis with polyangiitis (Wegener's) associated with dengue

Introducción: el dengue produce una activación del sistema inmune y en los pacientes conocidos portadores de enfermedades autoinmunes puede ser responsable de la activación de la enfermedad así como en los no conocidos puede revelar la enfermedad, por lo tanto ante un paciente con dengue con una presentación no habitual las enfermedades autoinmunes deben ser descartadas. Objetivo: presentar un paciente con dengue asociado a la activación de una vasculitis sistémica. Caso clínico: varón de 69 años, ingresó con cefalea, fiebre y mialgias en febrero 2012, el dengue fue sospechado y confirmado por serología IgM positiva. Debido a la persistencia de la fiebre, aparición de úlceras bucales, traqueales y nefritis asociada, se sospechó la poliangeitis granulomatosa (de Wegener) con ANCA-C positiva. Recibió tratamiento con pulsos de metilprednisolona y ciclofosfamida con regresión de las lesiones. Un mes después del alta fallece por insuficiencia respiratoria aguda secundaria a una estenosis subglótica secuela de la úlcera traqueal.

Introduction: Dengue produce an activation of the immune system in patients known to be carriers of autoimmune diseases, may be responsible for the activation of the disease as well as in unknown cases can reveal the disease itself, therefore a patient with dengue and unusual presentation, autoimmune disease should be ruled out. Objective: To present a patient with dengue associated with the activation of a systemic vasculitis. Case report: A 69 year old man was admitted with headache, fever and myalgia in February 2012, dengue was suspected and clinically confirmed by positive IgM serology. Due to persistent fever, oral and tracheal ulcers and associated nephritis, granulomatous polyangiitis (Wegener) with positive cANCA was suspected. She was treated with methylprednisolone and cyclophosphamide pulses with regression of lesions. One month after discharge, patient die from acute respiratory failure secondary to subglottic stenosis due to previous traqueal ulcer.

Neutrophil serine proteinases inactivate surfactant protein D by cleaving within a conserved subregion of the carbohydrate recognition domain.

Surfactant protein D (SP-D) plays important roles in innate immunity including the defense against bacteria, fungi, and respiratory viruses. Because SP-D specifically interacts with neutrophils that infiltrate the lung in response to acute inflammation and infection, we examined the hypothesis that the neutrophil-derived serine proteinases (NSPs): neutrophil elastase, proteinase-3, and cathepsin G degrade SP-D. All three human NSPs specifically cleaved recombinant rat and natural human SP-D dodecamers in a time- and dose-dependent manner, which was reciprocally dependent on calcium concentration. The NSPs generated similar, relatively stable, disulfide cross-linked immunoreactive fragments of approximately 35 kDa (reduced), and sequencing of a major catheptic fragment definitively localized the major sites of cleavage to a highly conserved subregion of the carbohydrate recognition domain. Cleavage markedly reduced the ability of SP-D to promote bacterial aggregation and to bind to yeast mannan in vitro. Incubation of SP-D with isolated murine neutrophils led to the generation of similar fragments, and cleavage was inhibited with synthetic and natural serine proteinase inhibitors. In addition, neutrophils genetically deficient in neutrophil elastase and/or cathepsin G were impaired in their ability to degrade SP-D. Using a mouse model of acute bacterial pneumonia, we observed the accumulation of SP-D at sites of neutrophil infiltration coinciding with the appearance of approximately 35-kDa SP-D fragments in bronchoalveolar lavage fluids. Together, our data suggest that neutrophil-derived serine proteinases cleave SP-D at sites of inflammation with potential deleterious effects on its biological functions.

Neutrophil serine proteinases cleave bacterial flagellin, abrogating its host response-inducing activity.

After bacterial infection, neutrophils dominate the cellular infiltrate. Their main function is assumed to be killing invading pathogens and resolving the inflammation they cause. Activated neutrophils are also known to release a variety of molecules, including the neutrophil serine proteinases, extracellularly. The release of these proteinases during inflammation creates a proteolytic environment where degradation of different molecules modulates the inflammatory response. Flagellin, the structural component of flagella on many bacterial species, is a virulence factor with a strong proinflammatory activity on epithelial cells and other cell types. In this study we show that both human and mouse neutrophil serine proteinases cleave flagellin from Pseudomonas aeruginosa and other bacterial species. More important, cleavage of P. aeruginosa flagellin by the neutrophil serine proteinases neutrophil elastase and cathepsin G resulted in loss of the biological activity of this virulence factor, as evidenced by the lack of innate host defense gene expression in human epithelial cells. The finding that flagellin is susceptible to cleavage by neutrophil serine proteinases suggests a novel role for these enzymes in the inflammatory response to infection. Not only can these enzymes kill bacteria, but they also degrade their virulence factors to halt the inflammatory response they trigger.