The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known.Thus,we sought to analyze the tempora...The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known.Thus,we sought to analyze the temporal profiles of specific antibodies,as well as the associations between the antibodies,proinflammatory cytokines,and survival of patients with coronavirus disease 2019(COVID-19).A total of 1830 laboratory-confirmed COVID-19 cases were recruited.The temporal profiles of the virus,antibodies,and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method.The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis.Of the 1830 patients,1435 were detectable for SARS-CoV-2,while 395 were positive in specific antibodies only.Of the 1435 patients,2.4%presented seroconversion for neither immunoglobulin G(IgG)nor immunoglobulin M(IgM)during hospitalization.The seropositive rates of IgG and IgM were 29.6%and 48.1%,respectively,in the first week,and plateaued within five weeks.For the patients discharged from the hospital,the IgM decreased slowly,while high levels of IgG were maintained at around 188 AUmL^(-1) for the 12 weeks since illness onset.In contrast,in the patients who subsequently died,IgM declined rapidly and IgG dropped to 87 AUmL^(-1) at the twelfth week.Elevated interleukin-6,interleukin-8,interleukin-10,interleukin-1b,interleukin-2R,and tumor necrosis factor-a levels were observed in the deceased patients in comparison with the discharged patients,and 12.5%of the association between IgG level and mortality risk was mediated by these cytokines.Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival,which may help to guide prognosis estimation.展开更多
Objectives: To find out the level and functions of Chlamydia trachomatis heat shock protein (C-hsp60) antibody, anti-spermantibody(ASAb), interleukin 1(IL-1), interleukin 6 (IL-6),interleukin 8 (IL-8), Tumor necrosis ...Objectives: To find out the level and functions of Chlamydia trachomatis heat shock protein (C-hsp60) antibody, anti-spermantibody(ASAb), interleukin 1(IL-1), interleukin 6 (IL-6),interleukin 8 (IL-8), Tumor necrosis factor alpha (TNF-α)and γ-interferon (IFN-γ) in patients with CT-related infertility. Methods: CT-DNA of cervical secretions was detectedthrough polymerase chain reaction (PCR) and migrationinhibiting factor (MIF) was employed to measure IgG titre ofCT MOMP antibody. Western blot was used to determinepresence of C-hsp60 antibody and enzyme-linkedimmunoadsorbent assay (ELISA) measured ASAb of IgG typein blood serum and determine the content of IL-1, IL-6. IL-8.TNF-α. IFN-γ in uterine tube fluid. Results: 68 patients had positive CT-DNA, among which 57(83.8%) had C-hsp60 antibody. Among the 172 patients withnegative CT-DNA, 64 patients (37.2%) also had C-hsp60Antibody. There was a significant difference (P<0.01) betweeninfertile patients and control group patients in the presence ofAAb. Infertile patients with positive CT-DNA had higher levels of IL-1、IL-6. IL-8. TNF-α. IFN-γ in uterine tube fluidcompared to control group patients (P<0.01). Conclusion: Firstly, those patients with negative CT testingfrom cervical secretions cannot be ruled out for CT infectionin deep parts of the body (such as oviduct, pelvic kidney).Detection of C-hsp60 Antibody may help to diagnose suchcases of CT. Secondly, CT infection of the oviduct can raiselevels of IL-1、IL-6、 IL-8、 TNF-α. IFN-γ. The pathogenesis ofinfertility caused by CT infection in the reproductive tractmay be related to cytokine production and inflammatoryresponses mediated by C-hsp60 Antibody, IL-1, IL-6, IL-8,TNF-α, and IFN-γ.展开更多
The expression and changes of local cytokines network were detected in heart transplantation in rats, so as to determine the role of cytokines in the acute rejection of rats of heart trans- plantation. Allografts were...The expression and changes of local cytokines network were detected in heart transplantation in rats, so as to determine the role of cytokines in the acute rejection of rats of heart trans- plantation. Allografts were divided into 4 groups （n=12 in each group）： group A （control）, group B （IL-2 monoclonal antibody-treated）, group C （CsA-treated） and group D （IL-2 monoclonal antibody＋CsA-treated）. Hearts from DA rats were transplanted into a cervical location in Wistar recipients. The local expression of IL-1β, IL-2, CD25, IL-4, IL-5, IL-6, IL-10, TNFα and INFy was detected at day 1, 3, 5, 7, 9, 11 and 14 by reverse transcription polymerase chain reaction. The results showed that the survival time of allografts was 8.3±1.7, 29.2±7.1 （P〈0.05）, 26.4±5.7 （P〈0.05） and 55.0±10.6 （P〈0.01） days respectively in groups A, B, C and D. The expression of IL-1β, IL-4, IL-10 and IFNy was up-regulated, and that of IL-2, CD25, IL-5, IL-6 and TNFα was significantly inhibited in group A; The expression of IL-1β, IL-5, IL-6, IL-10 and IFNy was up-regulated, and that of IL-2, IL-4 and TNFα was significantly down-regulated in group B; The expression of IL-1β, IL-2, CD25, IL-5, TNFα and IENγ was up-regulated, and that of IL-4, IL-6 and IL-10 was significantly down-regulated in group C; The expression of IL-14, 11-5, IL-6 and 11-10 was up-regulated, and that of IL-1β, IL-2, CD25, TNFα and IFNy was significantly down-regulated in group D. In conclusion, cytokines play an important role in the development of acute transplantation rejection. Different cytokines play different roles in different local environments.展开更多
Allergic disease is one of the most common chronic diseases,which can affect both children and adults,be often caused by allergen-induced unfavorable immune responses,and initiate various symptoms in different organs,...Allergic disease is one of the most common chronic diseases,which can affect both children and adults,be often caused by allergen-induced unfavorable immune responses,and initiate various symptoms in different organs,including up-/low-airways and skin,such as asthma,atopic dermatitis,and rhinosinusitis.With increasing prevalence of allergic disease worldwide and their impact on the quality of life,new biological therapeutic approaches for these disorders become hot areas of intensive research.Multiple factors are involved and play important role in the pathogenesis of allergic disease,which can promote or trigger T helper 2(Th2)-type immune responses,leading to production of the type 2 cytokines and immunoglobulin E(IgE),the two critical events in the allergic diseases.Using monoclonal antibodies to target these molecules,therefore,might provide possible benefits for the patients suffered from these diseases.Apart of those having approved biologics for allergic diseases,some potential targets such as epithelial-derived alarmins thymic stromal lymphopoietin(TSLP)and interleukin 33(IL-33)have been also described and proposed to develop monoclonal antibodies against either these cytokines,their receptors,or both.These new and potential targets have substantially enriched the therapeutic opportunities in the field of allergic diseases.The present review aims to briefly outline the role of monoclonal antibodies targeting the cytokines and immunoglobulin involved in the development of allergic diseases,and to discuss the clinical effects of these antibodies.展开更多
The use of adipose-derived cells as a treatment for a variety of diseases is becoming increasingly common. These therapies include the use of cultured mesenchymal stem cells (MSCs) and freshly isolated stromal vascula...The use of adipose-derived cells as a treatment for a variety of diseases is becoming increasingly common. These therapies include the use of cultured mesenchymal stem cells (MSCs) and freshly isolated stromal vascular fraction (SVF) alone, or in conjunction with other cells such as adipocytes. There is a substantial amount of literature published on the therapeutic properties of MSCs and their secretions as the main driver of their therapeutic effect. However, there is little data available on the therapeutic potential of secretions from SVF, either with or without adipocytes. We investigated the ability of secretions from human adipose SVF alone and the SVF co-cultured with adipocytes as a proxy for cell therapy, to ameliorate an inflammatory disorder. This ethics approved study involved the treatment of collagen antibody-induced arthritis (CAIA) in mice with secretions from SVF, SVF co-cultured with adipocytes, or a vehicle control via both intravenous (IV) and intramuscular (IM) routes. Treatment outcome was assessed by paw volume, ankle size and clinical arthritis score measurements. Serum samples were obtained following euthanasia and analysed for a panel of 32 mouse cytokines and growth factors. The dose and timing regime used for the IM administration of both human secretion mixtures did not significantly ameliorate arthritis in this model. The IV administration of SVF adipocyte co-culture secretions reduced the paw volume, and significantly reduced the ankle size and clinical arthritis score when compared to the IV vehicle control mice. This was a superior therapeutic effect than treatment with SVF secretions. Furthermore, treatment with SVF adipocyte coculture secretions resulted in a significant reduction in serum levels of key cytokines, IL-2 and VEGF, involved in the pathogenesis of rheumatoid arthritis. Therefore, the SVF cocultured with adipocytes is an attractive therapeutic for inflammatory conditions.展开更多
Children with Coronavirus Disease 2019(COVID-19) were reported to show milder symptoms and better prognosis than their adult counterparts, but the difference of immune response against SARS-CoV-2 between children and ...Children with Coronavirus Disease 2019(COVID-19) were reported to show milder symptoms and better prognosis than their adult counterparts, but the difference of immune response against SARS-CoV-2 between children and adults hasn’t been reported. Therefore we initiated this study to figure out the features of immune response in children with COVID-19.Sera and whole blood cells from 19 children with COVID-19 during different phases after disease onset were collected.The cytokine concentrations, SARS-CoV-2 S-RBD or N-specific antibodies and T cell immune responses were detected respectively. In children with COVID-19, only 3 of 12 cytokines were increased in acute sera, including interferon(IFN)-cinduced protein 10(IP10), interleukin(IL)-10 and IL-16. We observed an increase in T helper(Th)-2 cells and a suppression in regulatory T cells(Treg) in patients during acute phase, but no significant response was found in the IFN-cproducing or tumor necrosis factor(TNF)-a-producing CD8?T cells in patients. S-RBD and N IgM showed an early induction, while S-RBD and N IgG were prominently induced later in convalescent phase. Potent S-RBD IgA response was observed but N IgA seemed to be inconspicuous. Children with COVID-19 displayed an immunophenotype that is less inflammatory than adults, including unremarkable cytokine elevation, moderate CD4?T cell response and inactive CD8?T cell response, but their humoral immunity against SARS-CoV-2 were as strong as adults. Our finding presented immunological characteristics of children with COVID-19 and might give some clues as to why children develop less severe disease than adults.展开更多
基金supported by the National Natural Science Foundation of China(81572017)the National Key Research and Development Plan Program of China(2016YFC1302702 and 2020YFC0860800)+1 种基金the Revitalization Projects after the COVID-19 Plague of the China Association for Science and Technology(20200608CG111311)the Emergency Research Projects for COVID-19 Prevention and Control of the Wuhan Health Commission(EG20M01)。
文摘The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known.Thus,we sought to analyze the temporal profiles of specific antibodies,as well as the associations between the antibodies,proinflammatory cytokines,and survival of patients with coronavirus disease 2019(COVID-19).A total of 1830 laboratory-confirmed COVID-19 cases were recruited.The temporal profiles of the virus,antibodies,and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method.The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis.Of the 1830 patients,1435 were detectable for SARS-CoV-2,while 395 were positive in specific antibodies only.Of the 1435 patients,2.4%presented seroconversion for neither immunoglobulin G(IgG)nor immunoglobulin M(IgM)during hospitalization.The seropositive rates of IgG and IgM were 29.6%and 48.1%,respectively,in the first week,and plateaued within five weeks.For the patients discharged from the hospital,the IgM decreased slowly,while high levels of IgG were maintained at around 188 AUmL^(-1) for the 12 weeks since illness onset.In contrast,in the patients who subsequently died,IgM declined rapidly and IgG dropped to 87 AUmL^(-1) at the twelfth week.Elevated interleukin-6,interleukin-8,interleukin-10,interleukin-1b,interleukin-2R,and tumor necrosis factor-a levels were observed in the deceased patients in comparison with the discharged patients,and 12.5%of the association between IgG level and mortality risk was mediated by these cytokines.Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival,which may help to guide prognosis estimation.
基金The Project was funded by the Department of Education,Jangsu Province(Fund Number: 00KJD310003).
文摘Objectives: To find out the level and functions of Chlamydia trachomatis heat shock protein (C-hsp60) antibody, anti-spermantibody(ASAb), interleukin 1(IL-1), interleukin 6 (IL-6),interleukin 8 (IL-8), Tumor necrosis factor alpha (TNF-α)and γ-interferon (IFN-γ) in patients with CT-related infertility. Methods: CT-DNA of cervical secretions was detectedthrough polymerase chain reaction (PCR) and migrationinhibiting factor (MIF) was employed to measure IgG titre ofCT MOMP antibody. Western blot was used to determinepresence of C-hsp60 antibody and enzyme-linkedimmunoadsorbent assay (ELISA) measured ASAb of IgG typein blood serum and determine the content of IL-1, IL-6. IL-8.TNF-α. IFN-γ in uterine tube fluid. Results: 68 patients had positive CT-DNA, among which 57(83.8%) had C-hsp60 antibody. Among the 172 patients withnegative CT-DNA, 64 patients (37.2%) also had C-hsp60Antibody. There was a significant difference (P<0.01) betweeninfertile patients and control group patients in the presence ofAAb. Infertile patients with positive CT-DNA had higher levels of IL-1、IL-6. IL-8. TNF-α. IFN-γ in uterine tube fluidcompared to control group patients (P<0.01). Conclusion: Firstly, those patients with negative CT testingfrom cervical secretions cannot be ruled out for CT infectionin deep parts of the body (such as oviduct, pelvic kidney).Detection of C-hsp60 Antibody may help to diagnose suchcases of CT. Secondly, CT infection of the oviduct can raiselevels of IL-1、IL-6、 IL-8、 TNF-α. IFN-γ. The pathogenesis ofinfertility caused by CT infection in the reproductive tractmay be related to cytokine production and inflammatoryresponses mediated by C-hsp60 Antibody, IL-1, IL-6, IL-8,TNF-α, and IFN-γ.
文摘The expression and changes of local cytokines network were detected in heart transplantation in rats, so as to determine the role of cytokines in the acute rejection of rats of heart trans- plantation. Allografts were divided into 4 groups （n=12 in each group）： group A （control）, group B （IL-2 monoclonal antibody-treated）, group C （CsA-treated） and group D （IL-2 monoclonal antibody＋CsA-treated）. Hearts from DA rats were transplanted into a cervical location in Wistar recipients. The local expression of IL-1β, IL-2, CD25, IL-4, IL-5, IL-6, IL-10, TNFα and INFy was detected at day 1, 3, 5, 7, 9, 11 and 14 by reverse transcription polymerase chain reaction. The results showed that the survival time of allografts was 8.3±1.7, 29.2±7.1 （P〈0.05）, 26.4±5.7 （P〈0.05） and 55.0±10.6 （P〈0.01） days respectively in groups A, B, C and D. The expression of IL-1β, IL-4, IL-10 and IFNy was up-regulated, and that of IL-2, CD25, IL-5, IL-6 and TNFα was significantly inhibited in group A; The expression of IL-1β, IL-5, IL-6, IL-10 and IFNy was up-regulated, and that of IL-2, IL-4 and TNFα was significantly down-regulated in group B; The expression of IL-1β, IL-2, CD25, IL-5, TNFα and IENγ was up-regulated, and that of IL-4, IL-6 and IL-10 was significantly down-regulated in group C; The expression of IL-14, 11-5, IL-6 and 11-10 was up-regulated, and that of IL-1β, IL-2, CD25, TNFα and IFNy was significantly down-regulated in group D. In conclusion, cytokines play an important role in the development of acute transplantation rejection. Different cytokines play different roles in different local environments.
基金This work was supported by grants from the National Natural Science Foundation of China(81471594,81770049,and 81700026)the Natural Science Foundation of Beijing Municipality(7192023).
文摘Allergic disease is one of the most common chronic diseases,which can affect both children and adults,be often caused by allergen-induced unfavorable immune responses,and initiate various symptoms in different organs,including up-/low-airways and skin,such as asthma,atopic dermatitis,and rhinosinusitis.With increasing prevalence of allergic disease worldwide and their impact on the quality of life,new biological therapeutic approaches for these disorders become hot areas of intensive research.Multiple factors are involved and play important role in the pathogenesis of allergic disease,which can promote or trigger T helper 2(Th2)-type immune responses,leading to production of the type 2 cytokines and immunoglobulin E(IgE),the two critical events in the allergic diseases.Using monoclonal antibodies to target these molecules,therefore,might provide possible benefits for the patients suffered from these diseases.Apart of those having approved biologics for allergic diseases,some potential targets such as epithelial-derived alarmins thymic stromal lymphopoietin(TSLP)and interleukin 33(IL-33)have been also described and proposed to develop monoclonal antibodies against either these cytokines,their receptors,or both.These new and potential targets have substantially enriched the therapeutic opportunities in the field of allergic diseases.The present review aims to briefly outline the role of monoclonal antibodies targeting the cytokines and immunoglobulin involved in the development of allergic diseases,and to discuss the clinical effects of these antibodies.
文摘The use of adipose-derived cells as a treatment for a variety of diseases is becoming increasingly common. These therapies include the use of cultured mesenchymal stem cells (MSCs) and freshly isolated stromal vascular fraction (SVF) alone, or in conjunction with other cells such as adipocytes. There is a substantial amount of literature published on the therapeutic properties of MSCs and their secretions as the main driver of their therapeutic effect. However, there is little data available on the therapeutic potential of secretions from SVF, either with or without adipocytes. We investigated the ability of secretions from human adipose SVF alone and the SVF co-cultured with adipocytes as a proxy for cell therapy, to ameliorate an inflammatory disorder. This ethics approved study involved the treatment of collagen antibody-induced arthritis (CAIA) in mice with secretions from SVF, SVF co-cultured with adipocytes, or a vehicle control via both intravenous (IV) and intramuscular (IM) routes. Treatment outcome was assessed by paw volume, ankle size and clinical arthritis score measurements. Serum samples were obtained following euthanasia and analysed for a panel of 32 mouse cytokines and growth factors. The dose and timing regime used for the IM administration of both human secretion mixtures did not significantly ameliorate arthritis in this model. The IV administration of SVF adipocyte co-culture secretions reduced the paw volume, and significantly reduced the ankle size and clinical arthritis score when compared to the IV vehicle control mice. This was a superior therapeutic effect than treatment with SVF secretions. Furthermore, treatment with SVF adipocyte coculture secretions resulted in a significant reduction in serum levels of key cytokines, IL-2 and VEGF, involved in the pathogenesis of rheumatoid arthritis. Therefore, the SVF cocultured with adipocytes is an attractive therapeutic for inflammatory conditions.
基金supported by grants specific for Coronavirus Disease 2019 from the Children’s Hospital of Fudan University (Grant No. EKXGZX006)。
文摘Children with Coronavirus Disease 2019(COVID-19) were reported to show milder symptoms and better prognosis than their adult counterparts, but the difference of immune response against SARS-CoV-2 between children and adults hasn’t been reported. Therefore we initiated this study to figure out the features of immune response in children with COVID-19.Sera and whole blood cells from 19 children with COVID-19 during different phases after disease onset were collected.The cytokine concentrations, SARS-CoV-2 S-RBD or N-specific antibodies and T cell immune responses were detected respectively. In children with COVID-19, only 3 of 12 cytokines were increased in acute sera, including interferon(IFN)-cinduced protein 10(IP10), interleukin(IL)-10 and IL-16. We observed an increase in T helper(Th)-2 cells and a suppression in regulatory T cells(Treg) in patients during acute phase, but no significant response was found in the IFN-cproducing or tumor necrosis factor(TNF)-a-producing CD8?T cells in patients. S-RBD and N IgM showed an early induction, while S-RBD and N IgG were prominently induced later in convalescent phase. Potent S-RBD IgA response was observed but N IgA seemed to be inconspicuous. Children with COVID-19 displayed an immunophenotype that is less inflammatory than adults, including unremarkable cytokine elevation, moderate CD4?T cell response and inactive CD8?T cell response, but their humoral immunity against SARS-CoV-2 were as strong as adults. Our finding presented immunological characteristics of children with COVID-19 and might give some clues as to why children develop less severe disease than adults.
