RESUMO
Hemophagocytic lymphohistiocytosis is a life-threatening clinical syndrome caused by severe hypercytokinemia brought on by a highly stimulated but ineffective immune response. Animal studies and case series have demonstrated that a reduction in blood cytokine levels achieved with an extracorporeal adsorption cartridge that contains blood-compatible porous polymer beads (CytoSorb®) can effectively attenuate the inflammatory response during sepsis and possibly improve outcomes. We report a case series of two patients in which three episodes of severe hemophagocytic lymphohistiocytosis triggered by infections with herpesviridae were treated successfully with cytokine adsorption. A marked decrease in interleukin-6 plasma levels and a stable or decreasing need of vasopressor therapy were the most significant results of this treatment. Importantly, treatment was safe and well-tolerated, without any adverse events.
Assuntos
Citocinas/sangue , Linfo-Histiocitose Hemofagocítica/terapia , Diálise Renal/métodos , Adsorção , Adulto , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The development of erythroid progenitor cells is triggered via the expression of the erythropoietin receptor (EPOR) and its activation by erythropoietin. The function of the resulting receptor complex depends critically on the presence of activated JAK2, and the complex contains a large number of signaling molecules recruited to eight phosphorylated tyrosine residues. Studies using mutant receptor forms have demonstrated that truncated receptors lacking all tyrosines are able to support red blood cell development with low efficiency, whereas add-back mutants containing either Tyr343 or Tyr479 reconstitute EPOR signaling and erythropoiesis in vivo. To study the contribution of tyrosines to receptor function, we analyzed the activation of essential signaling pathways and early gene induction promoted by different receptor structural variants using human epidermal growth factor receptor/murine EPOR hybrids. In our experiments, receptors lacking all tyrosine residues or the JAK2-binding site did not induce mitogenic and anti-apoptotic signaling, whereas add-back mutant receptors containing single tyrosine residues (Try343 and Tyr479) supported the activation of these functions efficiently. Profiling of early gene expression using cDNA array hybridization revealed that (i) the high redundancy in the activation of signaling pathways is continued at the level of transcription; (ii) the expression of many genes targeted by the wild-type receptor is not supported by add-back mutants; and (iii) a small set of genes are exclusively induced by add-back receptors. We report the identification of several early genes that have not been implicated in the EPOR-dependent response so far.