BACKGROUND Acute pancreatitis(AP)is an inflammatory disease,which presents with epigastric pain and is clinically diagnosed by amylase and lipase three times the upper limit of normal.The 2012 Atlanta classification s...BACKGROUND Acute pancreatitis(AP)is an inflammatory disease,which presents with epigastric pain and is clinically diagnosed by amylase and lipase three times the upper limit of normal.The 2012 Atlanta classification stratifies the severity of AP as one of three risk categories namely,mild AP(MAP),moderately severe AP(MSAP),and severe AP(SAP).Challenges in stratifying AP upon diagnosis suggest that a better understanding of the underlying complex pathophysiology may be beneficial.AIM To identify the role of the chemokine receptor 8(CCR8),expressed by T-helper type-2 Lymphocytes and peritoneal macrophages,and its possible association to Interleukin(IL)-6 and AP stratification.METHODS This study was a prospective case-control study.A total of 40 patients were recruited from the Chris Hani Baragwanath Academic Hospital and the Charlotte Maxeke Johannesburg Academic Hospital.Bioassays were performed on 29 patients(14 MAP,11 MSAP,and 4 SAP)and 6 healthy controls as part of a preliminary study.A total of 12 mL of blood samples were collected at Day(D)1,3,5,and 7 post epigastric pain.Using multiplex immunoassay panels,real-time polymerase chain reaction(qRT-PCR)arrays,and multicolour flow cytometry analysis,immune response-related proteins,genes,and cells were profiled respectively.GraphPad Prism^(TM) software and fold change(FC)analysis was used to determine differences between the groups.P<0.05 was considered significant.RESULTS The concentration of IL-6 was significantly different at D3 post epigastric pain in both the MAP group and MSAP group with P=0.001 and P=0.013 respectively,in a multiplex assay.When a FC of 2 was applied to identify differentially expressed genes using RT2 Profiler,CCR8 was shown to increase steadily with disease severity from MAP(1.33),MSAP(38.28)to SAP(1172.45)median FC.Further verification studies using RT-PCR showed fold change increases of CCR8 in MSAP and SAP ranging from 1000 to 1000000 times when represented as Log10,compared to healthy control respectively at D3.The findings also showed differing lymphocyte and monocyte cell frequency between the groups.With monocyte population frequency as high as 70%in MSAP at D3.CONCLUSION The higher levels of CCR8 and IL-6 in the severe patients and immune cell differences compared to MAP and controls provide an avenue for exploring AP stratification to improve management.展开更多
Classical human leukocyte antigen(HLA)molecules of the major histocompatibility classⅡ(MHCⅡ)complex present peptides for the development,surveillance and activation of CD4^(+) T cells.The nonclassical MHCⅡ-like pro...Classical human leukocyte antigen(HLA)molecules of the major histocompatibility classⅡ(MHCⅡ)complex present peptides for the development,surveillance and activation of CD4^(+) T cells.The nonclassical MHCⅡ-like protein HLA-DM(DM)catalyzes the exchange and loading of peptides onto MHCⅡmolecules,thereby shaping MHCⅡimmunopeptidomes.Natural variations of DM in both chains of the protein(DMA and DMB)have been hypothesized to impact peptide presentation,but no evidence for altered function has been reported.Here we define the presence of DM allotypes in human populations covered by the 1000 Genomes Project and probe their activity.The functional properties of several allotypes are investigated and show strong enhancement of peptide-induced T cell activation for a particular combination of DMA and DMB.Biochemical evidence suggests a broader pH activity profile for the new variant relative to that of the most commonly expressed DM allotype.Immunopeptidome analysis indicates that the compartmental activity of the new DM heterodimer extends beyond the late endosome and suggests that the natural variation of DM has profound effects on adaptive immunity when antigens bypass the canonical processing pathway.展开更多
SUMMARY Vaccine-induced immune thrombotic thrombocytopenia(VITT)and cerebral venous sinus thrombosis(CVST)have been recently described as rare complications following vaccination against SARS-CoV-2 with vector vaccine...SUMMARY Vaccine-induced immune thrombotic thrombocytopenia(VITT)and cerebral venous sinus thrombosis(CVST)have been recently described as rare complications following vaccination against SARS-CoV-2 with vector vaccines.We report a case of a young woman who presented with VITT and cerebral CVST 7 days following vaccination with ChAdOx1 nCov-19(AstraZeneca).While the initial MRI was considered void of pathological findings,MRI 3 days later revealed extensive CVST of the transversal and sigmoidal sinus with intracerebral haemorrhage.Diagnostic tests including a platelet-factor-4-induced platelet activation assay confirmed the diagnosis of VITT.Treatment with intravenous immunoglobulins and argatroban resulted in a normalisation of platelet counts and remission of CVST.展开更多
基金Supported by the South African National Research Foundation,No.121277the University of the Witwatersrand Individual Research,No.001283844110151211055142the Faculty of Health Sciences,University of the Witwatersrand Seed Funding,No.0012518441101512110500000000000000004550.
文摘BACKGROUND Acute pancreatitis(AP)is an inflammatory disease,which presents with epigastric pain and is clinically diagnosed by amylase and lipase three times the upper limit of normal.The 2012 Atlanta classification stratifies the severity of AP as one of three risk categories namely,mild AP(MAP),moderately severe AP(MSAP),and severe AP(SAP).Challenges in stratifying AP upon diagnosis suggest that a better understanding of the underlying complex pathophysiology may be beneficial.AIM To identify the role of the chemokine receptor 8(CCR8),expressed by T-helper type-2 Lymphocytes and peritoneal macrophages,and its possible association to Interleukin(IL)-6 and AP stratification.METHODS This study was a prospective case-control study.A total of 40 patients were recruited from the Chris Hani Baragwanath Academic Hospital and the Charlotte Maxeke Johannesburg Academic Hospital.Bioassays were performed on 29 patients(14 MAP,11 MSAP,and 4 SAP)and 6 healthy controls as part of a preliminary study.A total of 12 mL of blood samples were collected at Day(D)1,3,5,and 7 post epigastric pain.Using multiplex immunoassay panels,real-time polymerase chain reaction(qRT-PCR)arrays,and multicolour flow cytometry analysis,immune response-related proteins,genes,and cells were profiled respectively.GraphPad Prism^(TM) software and fold change(FC)analysis was used to determine differences between the groups.P<0.05 was considered significant.RESULTS The concentration of IL-6 was significantly different at D3 post epigastric pain in both the MAP group and MSAP group with P=0.001 and P=0.013 respectively,in a multiplex assay.When a FC of 2 was applied to identify differentially expressed genes using RT2 Profiler,CCR8 was shown to increase steadily with disease severity from MAP(1.33),MSAP(38.28)to SAP(1172.45)median FC.Further verification studies using RT-PCR showed fold change increases of CCR8 in MSAP and SAP ranging from 1000 to 1000000 times when represented as Log10,compared to healthy control respectively at D3.The findings also showed differing lymphocyte and monocyte cell frequency between the groups.With monocyte population frequency as high as 70%in MSAP at D3.CONCLUSION The higher levels of CCR8 and IL-6 in the severe patients and immune cell differences compared to MAP and controls provide an avenue for exploring AP stratification to improve management.
基金supported by the Deutsche Forschungsgemeinschaft(DFG)C.F.is thankful for funding by the DFG(FR-1325/17–1,SFB958(project Z03)+1 种基金TRR186(projects A05,A11))M.A.-B.is thankful for funding from the Freie Universität Berlin Forschungskommision.
文摘Classical human leukocyte antigen(HLA)molecules of the major histocompatibility classⅡ(MHCⅡ)complex present peptides for the development,surveillance and activation of CD4^(+) T cells.The nonclassical MHCⅡ-like protein HLA-DM(DM)catalyzes the exchange and loading of peptides onto MHCⅡmolecules,thereby shaping MHCⅡimmunopeptidomes.Natural variations of DM in both chains of the protein(DMA and DMB)have been hypothesized to impact peptide presentation,but no evidence for altered function has been reported.Here we define the presence of DM allotypes in human populations covered by the 1000 Genomes Project and probe their activity.The functional properties of several allotypes are investigated and show strong enhancement of peptide-induced T cell activation for a particular combination of DMA and DMB.Biochemical evidence suggests a broader pH activity profile for the new variant relative to that of the most commonly expressed DM allotype.Immunopeptidome analysis indicates that the compartmental activity of the new DM heterodimer extends beyond the late endosome and suggests that the natural variation of DM has profound effects on adaptive immunity when antigens bypass the canonical processing pathway.
文摘SUMMARY Vaccine-induced immune thrombotic thrombocytopenia(VITT)and cerebral venous sinus thrombosis(CVST)have been recently described as rare complications following vaccination against SARS-CoV-2 with vector vaccines.We report a case of a young woman who presented with VITT and cerebral CVST 7 days following vaccination with ChAdOx1 nCov-19(AstraZeneca).While the initial MRI was considered void of pathological findings,MRI 3 days later revealed extensive CVST of the transversal and sigmoidal sinus with intracerebral haemorrhage.Diagnostic tests including a platelet-factor-4-induced platelet activation assay confirmed the diagnosis of VITT.Treatment with intravenous immunoglobulins and argatroban resulted in a normalisation of platelet counts and remission of CVST.
