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BackgroundKidney transplant recipients (KTRs) with COVID-19 have poor outcomes compared to non-KTRs. To provide insight into management of immunosuppression during acute illness, we studied immune signatures from the peripheral blood during and after COVID-19 infection from a multicenter KTR cohort.{square} MethodsClinical data were collected by chart review. PAXgene blood RNA was poly-A selected and RNA sequencing was performed to evaluate transcriptome changes. ResultsA total of 64 cases of COVID-19 in KTRs were enrolled, including 31 acute cases (< 4 weeks from diagnosis) and 33 post-acute cases (>4 weeks). In the blood transcriptome of acute cases, we identified differentially expressed genes (DEGs) in positive or negative association COVID-19 severity scores. Functional enrichment analyses showed upregulation of neutrophil and innate immune pathways, but downregulation of T-cell and adaptive immune-activation pathways proportional to severity score. This finding was independent of lymphocyte count and despite reduction in immunosuppression (IS) in most KTRs. Comparison with post-acute cases showed "normalization" of these enriched pathways after >4 weeks, suggesting recovery of adaptive immune system activation despite reinstitution of IS. The latter analysis was adjusted for COVID-19 severity score and lymphocyte count. DEGs associated with worsening disease severity in a non-KTR cohort with COVID-19 (GSE152418) showed significant overlap with KTRs in these identified enriched pathways. ConclusionBlood transcriptome of KTRs affected by COVID-19 shows decrease in T-cell and adaptive immune activation pathways during acute disease that associate with severity despite IS reduction and show recovery after acute illness. Significance statementKidney transplant recipients (KTRs) are reported to have worse outcomes with COVID-19, and empiric reduction of maintenance immunosuppression is pursued. Surprisingly, reported rates of acute rejection have been low despite reduced immunosuppression. We evaluated the peripheral blood transcriptome of 64 KTRs either during or after acute COVID-19. We identified transcriptomic signatures consistent with suppression of adaptive T-cell responses which significantly associated with disease severity and showed evidence of recovery after acute disease, even after adjustment for lymphocyte number. Our transcriptomic findings of immune-insufficiency during acute COVID-19 provide an explanation for the low rates of acute rejection in KTRs despite reduced immunosuppression. Our data support the approach of temporarily reducing T -cell-directed immunosuppression in KTRs with acute COVID-19.
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Objective To investigate the value of susceptibility weighted imaging in grading brain tumors in children.Methods Twenty-eight children with surgically or pathologically proved primary brain tumor were recruited during 2010 to 201 1.All patients were scanned with conventional MRI and SWI sequences on a 1.5T or 3.0T scanner before surgery.The cases of tumors were divid-ed into low grade (9 males and 2 females)and high grade groups (10 males and 7 females),according to the WHO classification of the tumors of the central nervous system in 2007.The low-intense signals within the abnormalities on SWI images were analyzed and classified into the different shapes,including punctuate,tubular,cluster-like,linear signal,irregular patchy signal.As for the num-ber of low-intense signals,we applied the four-score system.The irregular patchy signals were considered to be artifacts of SWI, namely hemorrhage,after exclusion of the isolated veins and calcification.The differences of rate of hemorrhage and scores between the two groups in SWI were analyzed statistically.Results The low-signal scores were significantly different between two groups with higher scores in high grade tumors than in low grade tumors(P <0.001).The rate of intratumor hemorrhage was also signifi-cantly different between two groups.The rate is higher in high-grade group than low-grade group,given the fact that the hemor-rhage was showed in 2 low grade tumors (18.18%),while in 1 1 high grade tumors (76.37%)(P =0.01 5 9<0.001).Conclusion Different grades of pediatric brain tumors manifest significant difference on susceptibility weighted imaging(SWI).It may be helpful in the preoperative classification of brain tumors by analyzing the relevant signals on SWI.
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Objective To investigate the MRI features of pilomyxoid astrocytoma ( PMA ) in children.Methods MRI features of seven children with pathologically proven PMA in 2011-2013 were retrospectively analyzed.The ages of the patients ranged from 10 months to 32 months at initial diagnosis.Results All tumors were well-circumscribed masses.Six tumors were located in the hypothalamic-chiasmatic-third ventricular region , two tumor involved the bilateral temporal lobe , and one tumor was associated with NF-I.One occurred in the basal ganglia region.Four tumors were solid masses , whereas the other three showed cystic components.Six tumors were hypointense and one was isointense on T 1-weighted image.Five tumors were hyperintense and three were isointense on T 2-weighted image.Four tumors were hypointense , one was iso-hypointense and one was isointense on DWI.After contrast administration , four tumors enhanced homogenously and three tumors enhanced heterogeneously , with intratumoral irregular hypointense region in two tumors and rim enhancement in one tumor.Cerebrospinal fluid ( CSF ) dissemination, hydrocephalus and peritumor edema were observed in 2, 4 and 1 of cases, respectively.Proton magnetic resonance spectrum of two PMA showed elevated Cho /Cr ratios and decreased NAA/Cr ratios.Conclusions The imaging features of pilomyxoid astrocytoma include common origination from the midline of the neuroaxis in younger children about 2-3 years old.The CSF dissemination is common.The presence of hemorrhage and peritumor edema is not common.
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ObjectiveTo study the biological characterization and the genetic background of circulating CA16 strains in mainland of China for the purpose of CA16 vaccine development in the future.MethodsCA16 strains were isolated from throat swabs of patients with hand-foot-mouth disease and identified by neutralization assay and RT-PCR.The genotype of these isolates were determined by sequence alignment and phylogenetic analysis of VP1 gene.The proliferation dynamics and the plaque morphology were observed when propagated in Vero cells.The pathogenicity of these CA16 isolates was evaluated by challenging newborn mice.ResultsIn this study,six CA16 circulating isolates,BJ-1-6 were obtained.The RT-PCR products were 150 bp amplified with the general enterovirus primers and 210 bp with CA16 primers respectively,which cannot be amplified by EV71 primers.Additionally,these isolates were identified to display some obvious proliferation dynamics and plaque morphology when propagated for 96 h in Vero cells.The diameter of plaques were about 1.5 to 2 mm for BJ-1,BJ-2,BJ-4,BJ-6,4-5 mm for BJ-3 and 3 mm for BJ5,the plaques were regular except BJ-3.All the six isolates can be neutralized by the convalescent serum of patient infected with CA16.The virus titer of different isolates propagated for five passages in Vero cells was 7.0LgCCID50/ml.The sequence alignment of VP1 gene demonstrated that the genotypes of BJ-2,BJ-4,BJ5 were C1 and BJ-1,BJ-3,B J-6 were C,3 comparatively.The genetic distance of the VPI gene from theseisolates suggested that they were highly genetic identity with the homology of 90％ in nucleotide and 99％ in dedicated amino acid respectively.However,a distinctive difference in pathogenic ability in neonatal mice was found that the suckling mice challenged with BJ-3 & BJ-5 were paralyzed 4-5 d and dead 6-7d postchallenge,compared with the control group without any abnormality in the during of 14 d.ConclusionThe circulating CA16 isolates in China have different biological characteristics,different pathogenic ability and similar genetic backgrounds,which is helpful for the development of a CA16 vaccine in the future.
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Objective To compare the adjuvanticity of type-A,B and C CpG-ODN in mice.Methods Three types of CpG-ODN were identified through in vitro stimulation of murine splenocytes with various CpG-ODN.BALB/c mice were immunized with HBsAg,together with different types of CpG-ODN,and antigen-specific IgG.IgG1 and IgG2a titers were measured 4 weeks later by indirect ELISA.Resuits Compared with the control group.all 3 types of CpG-ODN enhanced humoral immune response to HBsAg.However,type-B and C CpG-ODN induced much higher levels of antigen-specific IgG and IgG2a than type A CpG-ODN.Type-C CpG-ODN induced a similar TH 1-biased immune response as type-B CpG-ODN,revealed by decreased IsG1 to IgG2a ratio.In contrast,although type-A CpG-ODN increased IgG titers,it did not switch the balance between TH1 and TH2 immune responses.Conclusion All 3 types of CpG-ODN can enhance the humoral immune response to vaccines,but their aaiuvanticity could be mediated through different mechanisms.
