Background:The complement system plays an important role in the immune response to transplantation,and the diagnostic significance of peritubular capillary(PTC)C4d deposition(C4d+)in grafts is controversial.The study ...Background:The complement system plays an important role in the immune response to transplantation,and the diagnostic significance of peritubular capillary(PTC)C4d deposition(C4d+)in grafts is controversial.The study aimed to fully investigate the risk factors for PTC C4d+and analyze its significance in biopsy pathology of kidney transplantation.Methods:This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody(DSA)testing from January 2017 to December 2019 in a single center.The effects of recipient pathological indicators,eplet mismatch(MM),and DSAs on PTC C4d+were examined using univariate and multivariate logistic regression analyses.Results:In total,35/124(28%)were PTC C4d+,including 21 with antibody-mediated rejection(AMR),eight with renal tubular injury,three with T cell-mediated rejection,one with glomerular disease,and two others.Univariate analysis revealed that DSAs(P<0.001),glomerulitis(P<0.001),peritubular capillaritis(P<0.001),and human leukocyte antigen(HLA)B eplet MM(P=0.010)were the influencing factors of PTC C4d+.According to multivariate analysis,DSAs(odds ratio[OR]:9.608,95%confidence interval[CI]:2.742–33.668,P<0.001),glomerulitis(OR:3.581,95%CI:1.246–10.289,P=0.018),and HLA B eplet MM(OR:1.166,95%CI:1.005–1.353,P=0.042)were the independent risk factors for PTC C4d+.In receiver operating characteristic curve analysis,the area under the curve was increased to 0.831 for predicting PTC C4d+when considering glomerulitis,DSAs,and HLA B eplet MM.The proportions of HLA I DSAs and PTC C4d+in active antibody-mediated rejection were 12/17 and 15/17,respectively;the proportions of HLA class II DSAs and PTC C4d+in chronic AMR were 8/12 and 7/12,respectively.Furthermore,the higher the PTC C4d+score was,the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy.Conclusions:PTC C4d+was mainly observed in AMR cases.DSAs,glomerulitis,and HLA B eplet MM are the independent risk factors for PTC C4d+.展开更多
Anti-IgLON5 disease is a recently defined autoimmune disorder of the nervous system associated with autoantibodies against IgLON5. Given its broad clinical spectrum and extremely complex pathogenesis, as well as diffi...Anti-IgLON5 disease is a recently defined autoimmune disorder of the nervous system associated with autoantibodies against IgLON5. Given its broad clinical spectrum and extremely complex pathogenesis, as well as difficulties in its early diagnosis and treatment, anti-IgLON5 disease has become the subject of considerable research attention in the field of neuroimmunology. Anti-IgLON5 disease has characteristics of both autoimmunity and neurodegeneration due to the unique activity of the antiIgLON5 antibody. Neuropathologic examination revealed the presence of a tauopathy preferentially affecting the hypothalamus and brainstem tegmentum, potentially broadening our understanding of tauopathies. In contrast to that seen with other autoimmune encephalitis-related antibodies, basic studies have demonstrated that IgLON5 antibody-induced neuronal damage and degeneration are irreversible, indicative of a potential link between autoimmunity and neurodegeneration in antiIgLON5 disease. Herein, we comprehensively review and discuss basic and clinical studies relating to anti-IgLON5 disease to better understand this complicated disorder.展开更多
Objective To determine the in vitro expression of interleukin-12 (IL-12) and its effect on signal transducers and activators of transcription (STAT) signaling molecules in peripheral blood mononuclear cells (PBMCs) in...Objective To determine the in vitro expression of interleukin-12 (IL-12) and its effect on signal transducers and activators of transcription (STAT) signaling molecules in peripheral blood mononuclear cells (PBMCs) in patients with systemic lupus erythematosus (SLE).Methods Peripheral blood mononuclear cells in 39 patients with definite systemic lupus erythematosus and 11 healthy volunteers were collected. Expression of IL-12 P40mRNA in PBMCs was determined with reverse transcription-polymerase chain reaction (RT-PCR). Quantity of IL-12 protein supernatant was measured by enzyme-linked immunosorbent assay (ELISA). The levels of phosphorylated STAT3 and STAT4 signaling molecules in PBMCs were detected by immunoblot. Results Levels of IL-12 protein and mRNA expression in patients with active or inactive SLE were significantly higher than those in controls. Phytohemagglutinin (PHA) may promote the expression of IL-12. IL-12 alone induced the phosphorylation of STAT3 and STAT4 in PBMCs from patients with SLE, especially in active SLE. However it had no obvious effect on normal PBMCs. Phosphorylated STAT3 and STAT4 might be observed in normal PBMCs treated with IL-12 plus PHA.Conclusion IL-12 is produced aberrantly in patients with SLE. IL-12 might exert its biological role in SLE via the aberrantly phosphorylated STAT3 and STAT4 signaling molecules.展开更多
Objective： To assess if arachnoid cells have the capability to present antigen and activate T-lymphocytes after stimulation by bloody cerebrospinal fluid （CSF）, and to illuminate the mechanism of coagulation-initia...Objective： To assess if arachnoid cells have the capability to present antigen and activate T-lymphocytes after stimulation by bloody cerebrospinal fluid （CSF）, and to illuminate the mechanism of coagulation-initiated inflammation in the subarachnoid space after subarachnoid hemorrhage （SAH）. Methods： Arachnoid cells were cultured, characterized, and examined by immunofluorescence for the basal expression of human leukocyte antigen-DR （HLA-DR）, Expression of HLA-DR, after co-culturing arachnoid cells in vitro with bloody CSF, was investigated by immunofluorescence and flow cytometry （FCM）. The variation of arachnoid cells＇ ultrastructure was observed by transmission electron microscope （TEM）. Arachnoid cells were co-cultured with peripheral blood mononuclear cells （PBMCs）. The content of soluble interleukin-2 receptor （slL-2r） in culture medium was detected by enzyme-linked immunosorbent assay （ELISA）. Results： （1） Arachnoid cells were successfully cultured for many passages. The immunofluorescent staining was positive for HLA-DR in over 95% of the human arachnoid cells. The punctate HI_A-DR was distributed in cytoplasm and not in the karyon. （2） After co-culturing arachnoid cells in vitro with bloody CSF, numerous particles with strong fluorescence appeared in the cytoplasm on Day 6. On Day 8, the quantity of particles and fluorescent intensity were maximal. FCM showed that the percentage of HLA-DR expressing cells was （2.5＋_0.4）% at the first 5 d, increasing to （60.8＋_3.6）% on Day 7. （3） After co-culturing arachnoid cells in vitro with bloody CSF, many lysosome and secondary lysosome particles were present in the cytoplasm. Hyperplasia of rough endoplasmic re- ticulum and enlarged cysts were observed, with numerous phagocytizing vesicles also observed at the edge of the arachnoid cells. （4） Arachnoid cells stimulated by bloody CSF were co-cultured in vitro with PBMCs. The content of slL-2r in the culture medium, having been maintained at around 1.30 ng/ml during the first 3 d, had increased by Day 4. The content of slL-2r peaked 7.53 ng/ml on Day 7 and then reduced gradually. Conclusions： （1） Basic HLA-DR expression is present in arachnoid cells. （2） After stimulation by bloody CSF, arachnoid cells have the potential to serve as antigen presenting cells （APCs） and the ability to activate T-lymphocytes, indicating that arachnoid cells are involved in the mechanism of coagulation-initiated inflammation in the subarachnoid space after SAH.展开更多
Background: Human leukocyte antigen (HLA)-DR is a classical major histocompatibility complex (MHC) class II molecule encoded by five genes: HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4 and HLA-DRB5. The current study aimed t...Background: Human leukocyte antigen (HLA)-DR is a classical major histocompatibility complex (MHC) class II molecule encoded by five genes: HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4 and HLA-DRB5. The current study aimed to investigate the role of these genes in gliomas by analyzing microarray data. Methods: We enrolled 305 patients with histologically confirmed gliomas, and performed microarray data analysis along with studying their clinical characteristics. A new variable, termed HLA-DR score, was defined to explain the expression information of all five HLA-DR genes by factor analysis. HLA-DR scores in each grade of glioma and normal brain tissue were compared using one-way ANOVA. Lastly, correlations of HLA-DR scores with progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier and Cox analysis. Results: Our study indicated that an increased HLA-DR score, i.e. overexpression of HLA-DR genes, was correlated with a more aggressive glioma tumor grade (p < 0.001, One-way ANOVA). Moreover, the HLA-DR score was significantly higher in astrocytic tumors than oligodendroglial tumors (?0.718 ± 3.177 versus ?2.975 ± 2.662, t-test) in low-grade gliomas (LGGs). Kaplan-Meier analysis of both PFS (p = 0.046, log-rank test; p = 0.021, Breslow test) and OS (p = 0.029, Breslow test) showed significant differences in the clinical outcomes between LGG patients with high versus low HLA-DR scores. Finally, the HLA-DR score was further identified to be an independent prognostic factor of clinical outcomes by multivariate analysis (p = 0.042 and p = 0.025, for PFS and OS, respectively) in LGG patients. Conclusion: Expression of HLA-DR genes can be used to predict the tumor grade in gliomas, and the histological subtype in LGG. Furthermore, they are also an independent predictor for LGG patient survival.展开更多
基金the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University,China(No.XJTU1AF-CRF-2018-026)the Natural Science Foundation of China(No.82070768).
文摘Background:The complement system plays an important role in the immune response to transplantation,and the diagnostic significance of peritubular capillary(PTC)C4d deposition(C4d+)in grafts is controversial.The study aimed to fully investigate the risk factors for PTC C4d+and analyze its significance in biopsy pathology of kidney transplantation.Methods:This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody(DSA)testing from January 2017 to December 2019 in a single center.The effects of recipient pathological indicators,eplet mismatch(MM),and DSAs on PTC C4d+were examined using univariate and multivariate logistic regression analyses.Results:In total,35/124(28%)were PTC C4d+,including 21 with antibody-mediated rejection(AMR),eight with renal tubular injury,three with T cell-mediated rejection,one with glomerular disease,and two others.Univariate analysis revealed that DSAs(P<0.001),glomerulitis(P<0.001),peritubular capillaritis(P<0.001),and human leukocyte antigen(HLA)B eplet MM(P=0.010)were the influencing factors of PTC C4d+.According to multivariate analysis,DSAs(odds ratio[OR]:9.608,95%confidence interval[CI]:2.742–33.668,P<0.001),glomerulitis(OR:3.581,95%CI:1.246–10.289,P=0.018),and HLA B eplet MM(OR:1.166,95%CI:1.005–1.353,P=0.042)were the independent risk factors for PTC C4d+.In receiver operating characteristic curve analysis,the area under the curve was increased to 0.831 for predicting PTC C4d+when considering glomerulitis,DSAs,and HLA B eplet MM.The proportions of HLA I DSAs and PTC C4d+in active antibody-mediated rejection were 12/17 and 15/17,respectively;the proportions of HLA class II DSAs and PTC C4d+in chronic AMR were 8/12 and 7/12,respectively.Furthermore,the higher the PTC C4d+score was,the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy.Conclusions:PTC C4d+was mainly observed in AMR cases.DSAs,glomerulitis,and HLA B eplet MM are the independent risk factors for PTC C4d+.
基金supported by Shanghai Shuguang Plan Project,No. 18SG15Shanghai Outstanding Young Scholars Project+1 种基金Shanghai Talent Development Project,No. 2019044Clinical Research Plan of SHDC,No. SHDC 2020CR2027B (all to SC)。
文摘Anti-IgLON5 disease is a recently defined autoimmune disorder of the nervous system associated with autoantibodies against IgLON5. Given its broad clinical spectrum and extremely complex pathogenesis, as well as difficulties in its early diagnosis and treatment, anti-IgLON5 disease has become the subject of considerable research attention in the field of neuroimmunology. Anti-IgLON5 disease has characteristics of both autoimmunity and neurodegeneration due to the unique activity of the antiIgLON5 antibody. Neuropathologic examination revealed the presence of a tauopathy preferentially affecting the hypothalamus and brainstem tegmentum, potentially broadening our understanding of tauopathies. In contrast to that seen with other autoimmune encephalitis-related antibodies, basic studies have demonstrated that IgLON5 antibody-induced neuronal damage and degeneration are irreversible, indicative of a potential link between autoimmunity and neurodegeneration in antiIgLON5 disease. Herein, we comprehensively review and discuss basic and clinical studies relating to anti-IgLON5 disease to better understand this complicated disorder.
文摘Objective To determine the in vitro expression of interleukin-12 (IL-12) and its effect on signal transducers and activators of transcription (STAT) signaling molecules in peripheral blood mononuclear cells (PBMCs) in patients with systemic lupus erythematosus (SLE).Methods Peripheral blood mononuclear cells in 39 patients with definite systemic lupus erythematosus and 11 healthy volunteers were collected. Expression of IL-12 P40mRNA in PBMCs was determined with reverse transcription-polymerase chain reaction (RT-PCR). Quantity of IL-12 protein supernatant was measured by enzyme-linked immunosorbent assay (ELISA). The levels of phosphorylated STAT3 and STAT4 signaling molecules in PBMCs were detected by immunoblot. Results Levels of IL-12 protein and mRNA expression in patients with active or inactive SLE were significantly higher than those in controls. Phytohemagglutinin (PHA) may promote the expression of IL-12. IL-12 alone induced the phosphorylation of STAT3 and STAT4 in PBMCs from patients with SLE, especially in active SLE. However it had no obvious effect on normal PBMCs. Phosphorylated STAT3 and STAT4 might be observed in normal PBMCs treated with IL-12 plus PHA.Conclusion IL-12 is produced aberrantly in patients with SLE. IL-12 might exert its biological role in SLE via the aberrantly phosphorylated STAT3 and STAT4 signaling molecules.
基金Project supported by the National Natural Science Foundation of China (No. 30370497)the Science and Technology Research Program of Zhejiang Province,China (No. 2007-C-33039)
文摘Objective： To assess if arachnoid cells have the capability to present antigen and activate T-lymphocytes after stimulation by bloody cerebrospinal fluid （CSF）, and to illuminate the mechanism of coagulation-initiated inflammation in the subarachnoid space after subarachnoid hemorrhage （SAH）. Methods： Arachnoid cells were cultured, characterized, and examined by immunofluorescence for the basal expression of human leukocyte antigen-DR （HLA-DR）, Expression of HLA-DR, after co-culturing arachnoid cells in vitro with bloody CSF, was investigated by immunofluorescence and flow cytometry （FCM）. The variation of arachnoid cells＇ ultrastructure was observed by transmission electron microscope （TEM）. Arachnoid cells were co-cultured with peripheral blood mononuclear cells （PBMCs）. The content of soluble interleukin-2 receptor （slL-2r） in culture medium was detected by enzyme-linked immunosorbent assay （ELISA）. Results： （1） Arachnoid cells were successfully cultured for many passages. The immunofluorescent staining was positive for HLA-DR in over 95% of the human arachnoid cells. The punctate HI_A-DR was distributed in cytoplasm and not in the karyon. （2） After co-culturing arachnoid cells in vitro with bloody CSF, numerous particles with strong fluorescence appeared in the cytoplasm on Day 6. On Day 8, the quantity of particles and fluorescent intensity were maximal. FCM showed that the percentage of HLA-DR expressing cells was （2.5＋_0.4）% at the first 5 d, increasing to （60.8＋_3.6）% on Day 7. （3） After co-culturing arachnoid cells in vitro with bloody CSF, many lysosome and secondary lysosome particles were present in the cytoplasm. Hyperplasia of rough endoplasmic re- ticulum and enlarged cysts were observed, with numerous phagocytizing vesicles also observed at the edge of the arachnoid cells. （4） Arachnoid cells stimulated by bloody CSF were co-cultured in vitro with PBMCs. The content of slL-2r in the culture medium, having been maintained at around 1.30 ng/ml during the first 3 d, had increased by Day 4. The content of slL-2r peaked 7.53 ng/ml on Day 7 and then reduced gradually. Conclusions： （1） Basic HLA-DR expression is present in arachnoid cells. （2） After stimulation by bloody CSF, arachnoid cells have the potential to serve as antigen presenting cells （APCs） and the ability to activate T-lymphocytes, indicating that arachnoid cells are involved in the mechanism of coagulation-initiated inflammation in the subarachnoid space after SAH.
文摘Background: Human leukocyte antigen (HLA)-DR is a classical major histocompatibility complex (MHC) class II molecule encoded by five genes: HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4 and HLA-DRB5. The current study aimed to investigate the role of these genes in gliomas by analyzing microarray data. Methods: We enrolled 305 patients with histologically confirmed gliomas, and performed microarray data analysis along with studying their clinical characteristics. A new variable, termed HLA-DR score, was defined to explain the expression information of all five HLA-DR genes by factor analysis. HLA-DR scores in each grade of glioma and normal brain tissue were compared using one-way ANOVA. Lastly, correlations of HLA-DR scores with progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier and Cox analysis. Results: Our study indicated that an increased HLA-DR score, i.e. overexpression of HLA-DR genes, was correlated with a more aggressive glioma tumor grade (p < 0.001, One-way ANOVA). Moreover, the HLA-DR score was significantly higher in astrocytic tumors than oligodendroglial tumors (?0.718 ± 3.177 versus ?2.975 ± 2.662, t-test) in low-grade gliomas (LGGs). Kaplan-Meier analysis of both PFS (p = 0.046, log-rank test; p = 0.021, Breslow test) and OS (p = 0.029, Breslow test) showed significant differences in the clinical outcomes between LGG patients with high versus low HLA-DR scores. Finally, the HLA-DR score was further identified to be an independent prognostic factor of clinical outcomes by multivariate analysis (p = 0.042 and p = 0.025, for PFS and OS, respectively) in LGG patients. Conclusion: Expression of HLA-DR genes can be used to predict the tumor grade in gliomas, and the histological subtype in LGG. Furthermore, they are also an independent predictor for LGG patient survival.
