Objective Preliminary assessment of rabies virus neutralizing activity,safety and immunogenicity of a recombinant human rabies antibody(NM57)compared with human rabies immunoglobulin(HRIG)in Chinese healthy adults.Met...Objective Preliminary assessment of rabies virus neutralizing activity,safety and immunogenicity of a recombinant human rabies antibody(NM57)compared with human rabies immunoglobulin(HRIG)in Chinese healthy adults.Methods Subjects were randomly(1:1:1)allocated to Groups A(20 IU/kg NM57),B(40 IU/kg NM57),or C(20 IU/kg HRIG).One injection was given on the day of enrollment.Blood samples were collected on days-7 to 0(pre-injection),3,7,14,28,and 42.Adverse events(AEs)and serious AEs(SAEs)were recorded over a period of 42 days after injection.Results All 60 subjects developed detectable rabies virus neutralizing antibodies(RVNAs)(>0.05 IU/mL)on days 3,7,14,28,and 42.The RVNA levels peaked on day 3 in all three groups,with a geometric mean concentration(GMC)of 0.2139 IU/mL in Group A,0.3660 IU/mL in Group B,and0.1994 IU/mL in Group C.At each follow-up point,the GMC in Group B was significantly higher than that in Groups A and C.The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C.Fifteen AEs were reported.Except for one grade 2 myalgia in Group C,the other 14 were all grade 1.No SAEs were observed.Conclusion The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG,and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar.Safety was comparable between NM57 and HRIG.展开更多
Human papillomaviruses(HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and s...Human papillomaviruses(HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. Many HPVs, considered lowrisk such as HPV 6 and 11, produce warts; while highrisk viruses, such as HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. About 5% of all cancers in men and women are associated with HPV infection. Because there are not antiviral drugs for HPV infection, current therapies for low-risk HPV infections involve physical removal of the lesion by cryotherapy, trichloracetic acid, laser, or surgical removal. Surgical procedures are effective in the treatment of precancerous lesions, however after these procedures, many recurrences appear due to new re-infections, or to failure of the procedure to eliminate the HPV. In addition, HPV can inhibit recognition of malignant cellsby the immune system, leading to the development of cancer lesions. When this occurs, radiotherapy and chemotherapy are then used. Unfortunately, about 50% of the HPV-cancer patients still die. In the past decade, a better knowledge of the natural history of the virushost interaction and of the immune response against this viral infection has brought new therapeutic strategies geared to modulate the immune system to generate an efficient virus-specific cytotoxic response. Novel HPV protein-expressing vaccines have shown some significant clinical efficacy and systemic HPV-specific cytotoxic T cell responses. This review will describe the current status of the several therapeutic strategies used to treat HPV-induced lesions, and discuss the various new therapies now being tested.展开更多
BACKGROUND Acquired pure red cell aplasia(aPRCA)related to human parvovirus B19(HPV B19)is rarely reported in simultaneous pancreas-kidney transplantation(SPKT)recipients;there has yet to be a case report of early pos...BACKGROUND Acquired pure red cell aplasia(aPRCA)related to human parvovirus B19(HPV B19)is rarely reported in simultaneous pancreas-kidney transplantation(SPKT)recipients;there has yet to be a case report of early postoperative infection.In this current study,we report the case of a Chinese patient who experienced the disease in the early postoperative period.CASE SUMMARY A 63-year-old man,with type 2 diabetes and end-stage renal disease,received a brain dead donor-derived SPKT.Immunosuppression treatment consisted of tacrolimus,prednisone,enteric-coated mycophenolate sodium(EC-MPS),and thymoglobulin combined with methylprednisolone as induction.The hemoglobin(Hb)level declined due to melena at postoperative day(POD)3,erythropoietinresistant anemia persisted,and reticulocytopenia was diagnosed at POD 20.The bone marrow aspirate showed decreased erythropoiesis and the presence of giant pronormoblasts at POD 43.Metagenomic next-generation sequencing(mNGS)of a blood sample identified HPV B19 infection at POD 66.EC-MPS was withdrawn;three cycles of intravenous immunoglobulin(IVIG)infusion therapy were administered;and tacrolimus was switched to cyclosporine.The HPV B19-associated aPRCA resolved completely and did not relapse within the 1-year follow-up period.The diminution in mNGS reads was correlated with Hb and reticulocyte count improvements.CONCLUSION HPV B19-associated aPRCA can occur at an early period after SPKT.An effective therapy regimen includes IVIG infusion and adjustment of the immunosuppressive regimen.Moreover,mNGS can be used for the diagnosis and to reflect disease progression.展开更多
AIM: To assess potential contributions of biliary IgA for crystal agglomeration into gallstones, we visualized cholesterol crystal binding of biliary IgA. METHODS: Crystal binding biliary proteins were extracted from ...AIM: To assess potential contributions of biliary IgA for crystal agglomeration into gallstones, we visualized cholesterol crystal binding of biliary IgA. METHODS: Crystal binding biliary proteins were extracted from human gallbladder bile using lectin affinity chromatography.Biliary IgA was isolated from the bound protein fraction by immunoaffinity chromatography. Pure cholesterol monohydrate crystals were incubated with biliary IgA and fluoresceine isothiocyanate (FITC)conjugated anti IgA at 37 degree. Samples were examined under polarizing and fluorescence light microscopy with digital image processing. RESULTS: Binding of biliary IgA to cholesterol monohydrate crystals could be visualized with FITC conjugated anti IgA antibodies.Peak fluorescence occurred at crystal edges and dislocations. Controls without biliary IgA or with biliary IgG showed no significant fluorescence. CONCLUSION: Fluorescence light microscopy provided evidence for cholesterol crystal binding of biliary IgA. Cholesterol crystal binding proteins like IgA might be important mediators of crystal agglomeration and growth of cholesterol gallstones by modifying the evolving crystal structures in vivo.展开更多
Cytomegalovirus (CMV) is an important pathogen in immunocompromised individuals. Coupled with Human Immunodeficiency Virus (HIV), it causes end organ diseases leading to increased morbidity and mortality in the popula...Cytomegalovirus (CMV) is an important pathogen in immunocompromised individuals. Coupled with Human Immunodeficiency Virus (HIV), it causes end organ diseases leading to increased morbidity and mortality in the population. The prevalence of Cytomegalovirus infection is above 93% in HIV infected children in Kenya. Despite, a high Cytomegalovirus seroprevalence found in children, few studies have documented CMV in adults. This study was done to determine the seroprevalence of CMV infection and its associated risk factors among HIV patients attending Thika level 5 Hospital in Kiambu County, Kenya. The study also evaluated the effect CMV infection on the immunity of HIV infected patients. A cross-sectional study involving 163 HIV positive participants from different age groups was carried out. A questionnaire was used to assess the socio-demographic and specific risk factors associated with cytomegalovirus. Blood was collected and analyzed for CD4 counts, CMV IgG and IgM. The seroprevalence of CMV was found to be 89% (CMV IgG) while the incidence was 10.4% (CMV IgM). The study found that CMV infection leads to more suppression of the immunity among the HIV infected patients. In addition, education, economic status, having other sexual transmitted infections, sharing drinks, immune status and blood transfusion were associated with CMV infection (p < 0.05). The study recommends adoption of CMV screening services and education on CMV risk factors as CMV infection preventive strategies.展开更多
Chromosomes in human-mouse and human-(human-mouse)hybridomas wereanalysed by G-banding methods.It was found that most human chromosomes,exceptNo.13 and X,Y,were retained.The frequencies of chromosomes No.1,3,4,5,6,17,...Chromosomes in human-mouse and human-(human-mouse)hybridomas wereanalysed by G-banding methods.It was found that most human chromosomes,exceptNo.13 and X,Y,were retained.The frequencies of chromosomes No.1,3,4,5,6,17,19,21 and 22 were higher than those of other chromosomes in each hybridoma clone.The myeloma cell lines X63-Ag8.653 and SHM-D33 were also analysed.The morphologyof marker chromosomes was apparently different between hybridomas.There were 7 kindsof marker chromosomes in human-mouse hybridomas and 16 kinds of markerchromosomes in human-(human-mouse)hybridomas.Clones that retained humanchromosome No.1 were more stable and clones that did not retain human chromosomeNo.14 were still capable of secreting human immunoglobulin.Clones that retained humanchromosome No.2 did not secret human k light chain McAb while clones that retainedhuman chromosomes No.2 and No.22 only secreted λ light chain.展开更多
Therapeutic immunoglobulins are used in the treatment of immunodeficiencies as well as several autoimmune and inflammatory diseases. These intravenous immunoglobulins (IVIg) represent the healthy human IgG repertoire,...Therapeutic immunoglobulins are used in the treatment of immunodeficiencies as well as several autoimmune and inflammatory diseases. These intravenous immunoglobulins (IVIg) represent the healthy human IgG repertoire, which can be reactive for both self and non-self antigens. A better characterization of IVIg’s repertoire is an important aspect to enable its effective utilization as an immunomodulatory treatment. In this study we have investigated the reactivity of IgG1, IgG2, IgG3 and IgG4 present in IVIg for a small selection of antigens, including actin, DNA, ferritin and thyroglobulin. We observed that two commercial preparations of therapeutic immunoglobulins contain very high reactivity for thyroglobulin, which was predominantly detected by IgG4. Since IgG4 antibodies can have immunomodulatory properties, these result suggest that these anti-thyroglobulin may have a role in the IVIg treatment of autoimmune disease characterized by high avidity for anti-thyroglobulin antibodies such as Hashimoto’s disease.展开更多
基金supported by 2021 Beijing Key Specialty Program for Major Epidemic Prevention and Control。
文摘Objective Preliminary assessment of rabies virus neutralizing activity,safety and immunogenicity of a recombinant human rabies antibody(NM57)compared with human rabies immunoglobulin(HRIG)in Chinese healthy adults.Methods Subjects were randomly(1:1:1)allocated to Groups A(20 IU/kg NM57),B(40 IU/kg NM57),or C(20 IU/kg HRIG).One injection was given on the day of enrollment.Blood samples were collected on days-7 to 0(pre-injection),3,7,14,28,and 42.Adverse events(AEs)and serious AEs(SAEs)were recorded over a period of 42 days after injection.Results All 60 subjects developed detectable rabies virus neutralizing antibodies(RVNAs)(>0.05 IU/mL)on days 3,7,14,28,and 42.The RVNA levels peaked on day 3 in all three groups,with a geometric mean concentration(GMC)of 0.2139 IU/mL in Group A,0.3660 IU/mL in Group B,and0.1994 IU/mL in Group C.At each follow-up point,the GMC in Group B was significantly higher than that in Groups A and C.The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C.Fifteen AEs were reported.Except for one grade 2 myalgia in Group C,the other 14 were all grade 1.No SAEs were observed.Conclusion The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG,and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar.Safety was comparable between NM57 and HRIG.
基金Supported by Dirección General de Asuntos del Personal Académico,Universidad Nacional Autónoma de México No.IN207514Consejo Nacional de Ciencia y Tecnología,Mexico,No.168098
文摘Human papillomaviruses(HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. Many HPVs, considered lowrisk such as HPV 6 and 11, produce warts; while highrisk viruses, such as HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. About 5% of all cancers in men and women are associated with HPV infection. Because there are not antiviral drugs for HPV infection, current therapies for low-risk HPV infections involve physical removal of the lesion by cryotherapy, trichloracetic acid, laser, or surgical removal. Surgical procedures are effective in the treatment of precancerous lesions, however after these procedures, many recurrences appear due to new re-infections, or to failure of the procedure to eliminate the HPV. In addition, HPV can inhibit recognition of malignant cellsby the immune system, leading to the development of cancer lesions. When this occurs, radiotherapy and chemotherapy are then used. Unfortunately, about 50% of the HPV-cancer patients still die. In the past decade, a better knowledge of the natural history of the virushost interaction and of the immune response against this viral infection has brought new therapeutic strategies geared to modulate the immune system to generate an efficient virus-specific cytotoxic response. Novel HPV protein-expressing vaccines have shown some significant clinical efficacy and systemic HPV-specific cytotoxic T cell responses. This review will describe the current status of the several therapeutic strategies used to treat HPV-induced lesions, and discuss the various new therapies now being tested.
基金National Natural Science Foundation of,No.81970654.
文摘BACKGROUND Acquired pure red cell aplasia(aPRCA)related to human parvovirus B19(HPV B19)is rarely reported in simultaneous pancreas-kidney transplantation(SPKT)recipients;there has yet to be a case report of early postoperative infection.In this current study,we report the case of a Chinese patient who experienced the disease in the early postoperative period.CASE SUMMARY A 63-year-old man,with type 2 diabetes and end-stage renal disease,received a brain dead donor-derived SPKT.Immunosuppression treatment consisted of tacrolimus,prednisone,enteric-coated mycophenolate sodium(EC-MPS),and thymoglobulin combined with methylprednisolone as induction.The hemoglobin(Hb)level declined due to melena at postoperative day(POD)3,erythropoietinresistant anemia persisted,and reticulocytopenia was diagnosed at POD 20.The bone marrow aspirate showed decreased erythropoiesis and the presence of giant pronormoblasts at POD 43.Metagenomic next-generation sequencing(mNGS)of a blood sample identified HPV B19 infection at POD 66.EC-MPS was withdrawn;three cycles of intravenous immunoglobulin(IVIG)infusion therapy were administered;and tacrolimus was switched to cyclosporine.The HPV B19-associated aPRCA resolved completely and did not relapse within the 1-year follow-up period.The diminution in mNGS reads was correlated with Hb and reticulocyte count improvements.CONCLUSION HPV B19-associated aPRCA can occur at an early period after SPKT.An effective therapy regimen includes IVIG infusion and adjustment of the immunosuppressive regimen.Moreover,mNGS can be used for the diagnosis and to reflect disease progression.
文摘AIM: To assess potential contributions of biliary IgA for crystal agglomeration into gallstones, we visualized cholesterol crystal binding of biliary IgA. METHODS: Crystal binding biliary proteins were extracted from human gallbladder bile using lectin affinity chromatography.Biliary IgA was isolated from the bound protein fraction by immunoaffinity chromatography. Pure cholesterol monohydrate crystals were incubated with biliary IgA and fluoresceine isothiocyanate (FITC)conjugated anti IgA at 37 degree. Samples were examined under polarizing and fluorescence light microscopy with digital image processing. RESULTS: Binding of biliary IgA to cholesterol monohydrate crystals could be visualized with FITC conjugated anti IgA antibodies.Peak fluorescence occurred at crystal edges and dislocations. Controls without biliary IgA or with biliary IgG showed no significant fluorescence. CONCLUSION: Fluorescence light microscopy provided evidence for cholesterol crystal binding of biliary IgA. Cholesterol crystal binding proteins like IgA might be important mediators of crystal agglomeration and growth of cholesterol gallstones by modifying the evolving crystal structures in vivo.
文摘Cytomegalovirus (CMV) is an important pathogen in immunocompromised individuals. Coupled with Human Immunodeficiency Virus (HIV), it causes end organ diseases leading to increased morbidity and mortality in the population. The prevalence of Cytomegalovirus infection is above 93% in HIV infected children in Kenya. Despite, a high Cytomegalovirus seroprevalence found in children, few studies have documented CMV in adults. This study was done to determine the seroprevalence of CMV infection and its associated risk factors among HIV patients attending Thika level 5 Hospital in Kiambu County, Kenya. The study also evaluated the effect CMV infection on the immunity of HIV infected patients. A cross-sectional study involving 163 HIV positive participants from different age groups was carried out. A questionnaire was used to assess the socio-demographic and specific risk factors associated with cytomegalovirus. Blood was collected and analyzed for CD4 counts, CMV IgG and IgM. The seroprevalence of CMV was found to be 89% (CMV IgG) while the incidence was 10.4% (CMV IgM). The study found that CMV infection leads to more suppression of the immunity among the HIV infected patients. In addition, education, economic status, having other sexual transmitted infections, sharing drinks, immune status and blood transfusion were associated with CMV infection (p < 0.05). The study recommends adoption of CMV screening services and education on CMV risk factors as CMV infection preventive strategies.
文摘Chromosomes in human-mouse and human-(human-mouse)hybridomas wereanalysed by G-banding methods.It was found that most human chromosomes,exceptNo.13 and X,Y,were retained.The frequencies of chromosomes No.1,3,4,5,6,17,19,21 and 22 were higher than those of other chromosomes in each hybridoma clone.The myeloma cell lines X63-Ag8.653 and SHM-D33 were also analysed.The morphologyof marker chromosomes was apparently different between hybridomas.There were 7 kindsof marker chromosomes in human-mouse hybridomas and 16 kinds of markerchromosomes in human-(human-mouse)hybridomas.Clones that retained humanchromosome No.1 were more stable and clones that did not retain human chromosomeNo.14 were still capable of secreting human immunoglobulin.Clones that retained humanchromosome No.2 did not secret human k light chain McAb while clones that retainedhuman chromosomes No.2 and No.22 only secreted λ light chain.
文摘Therapeutic immunoglobulins are used in the treatment of immunodeficiencies as well as several autoimmune and inflammatory diseases. These intravenous immunoglobulins (IVIg) represent the healthy human IgG repertoire, which can be reactive for both self and non-self antigens. A better characterization of IVIg’s repertoire is an important aspect to enable its effective utilization as an immunomodulatory treatment. In this study we have investigated the reactivity of IgG1, IgG2, IgG3 and IgG4 present in IVIg for a small selection of antigens, including actin, DNA, ferritin and thyroglobulin. We observed that two commercial preparations of therapeutic immunoglobulins contain very high reactivity for thyroglobulin, which was predominantly detected by IgG4. Since IgG4 antibodies can have immunomodulatory properties, these result suggest that these anti-thyroglobulin may have a role in the IVIg treatment of autoimmune disease characterized by high avidity for anti-thyroglobulin antibodies such as Hashimoto’s disease.
