RESUMEN
OBJECTIVE: Dendritic cells (DCs) are critical effectors of innate and adaptive immunity playing crucial roles in autoimmune responses. We previously showed that blood DC numbers were reduced in autoimmune antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV). Here, we assessed toll-like receptor (TLR) responsiveness of blood DCs from patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). METHODS: Blood samples from healthy controls (HCs), GPA, or MPA patients, without treatment, during acute phase (AP) or remission phase (RP) were analyzed. Cytokine production by DCs and T cells was assessed on whole blood by flow cytometry after TLRs or polyclonal stimulation, respectively. RESULTS: We first showed that GPA and MPA are associated with a decreased blood DC number during AP. Conventional DCs (cDCs) from patients with GPA and MPA in AP exhibited a profound decrease of IL-12/IL-23p40 production after TLR3, 4, or 7/8 stimulation compared to patients in remission and HC, with a return to normal values in RP. TNFα secretion was also affected, with a decrease in cDCs from GPA patients in AP after TLR3 stimulation but an increase after TLR7/8 stimulation. By contrast, the responsiveness of plasmacytoid DCs to TLR7 and 9 was only marginally affected. Finally, we observed that IFNγ-producing CD4+ T cell frequency was significantly lower in AP-GPA patients than in HC. CONCLUSION: We describe, for the first time, a dysregulated response to TLRs of circulating DCs in AAV patients mostly affecting cDCs that exhibit an unexpected reduced inflammatory cytokine secretion possibly contributing to an altered Th cell response.
RESUMEN
PURPOSE: Critically ill patients often require CT scans. Adverse events (AE) can occur during intra-hospital transport (IHT). The aim of this prospective study was to determine the diagnostic and therapeutic yield and the safety of CT scans in ICU patients. METHODS: All ICU patients having a CT scan for diagnostic purposes were eligible. Diagnostic yield was evaluated by the agreement (full, partial or disagreement) between the physician main diagnostic hypothesis before the CT scan and the diagnosis established after the CT scan. Therapeutic yield was assessed by therapeutic changes after the CT scan. The safety was determined by the AE rate during IHT. RESULTS: A total of 533 CT scans were performed on 359 patients in three teaching hospital ICUs. The diagnostic yield of CT scan showed 40.7 % of full agreement, 5.6 % of partial agreement and 53.7 % of disagreement with the main diagnostic hypothesis formulated before the CT scan. The CT-scan brought new elements to the diagnosis in 22.9 % of the cases. There was 54.4 % of therapeutic change after CT scan, while 22.3 % of AE occurred during IHT, including 6.7 % of life-threatening events. AE occurred more frequently in the first 48 h after ICU admission, in the most severely ill patients (higher SAPS II at admission), and when there was a large amount of equipment required for transport. CONCLUSIONS: The CT scan as a diagnostic procedure invalidated a diagnostic hypothesis and led to a therapeutic change in more than half of the cases.
